Ss t and h

“TOBACCO AND HEALTH”
By
Dr. N.S. ARUNGANI,
LIBRARY DISSERTATION
MASTER OF DENTAL SURGERY
IN
DEPARTMENT OF ORAL AND MAXILLOFACIAL PATHOLOGY AND ORAL
MICROBIOLOGY
Under the guidance of
Dr. R. SUGANYA, M.D.S.,
READER
Under the Co-guidance of
Dr. K.R. PREMLAL, M.D.S.,
READER
DEPARTMENT OF ORAL AND MAXILLOFACIAL PATHOLOGY AND ORAL
MICROBIOLOGY
INDIRA GANDHI INSTITUTE OF DENTAL SCIENCES
PUDUCHERRY – 607402
2019 - 2022

DECLARATION BY THE CANDIDATE
I hereby declare that this LIBRARY DISSERTATION entitled “TOBACCO AND
HEALTH” is a bonafide and genuine work carried out by me under the guidance of Dr. R.
SUGANYA, M.D.S., READER, co-guidance of Dr. K.R. PREMLAL,
M.D.S., READER, DEPARTMENT OF ORAL AND MAXILLOFACIAL PATHOLOGY
AND ORAL MICROBIOLOGY, Indira Gandhi Institute of Dental Sciences, Sri Balaji
Vidyapeeth, Puducherry.

ACKNOWLEDGEMENT
Preeminently I would like to praise and thank God, the Almighty for showering his blessings,
I would like to thank my Family, Mr. A.R. Seakaran, Mrs. S.S. Vennila for their constant love and
support through the thick and thin.
I sincerely thank Our Chancellor Shri. M.K. Rajagopalan, Vice Chancellor Dr. Subash
Chandra Parija and The Principal, Dr. R. Saravana Kumar, IGIDS for providing all the facilities to
finish this library dissertation.
I truly thank Dr. A. Santha Devy, Head of the Department for her continuous support and
encouragement.
I would like to express my deepest gratitude to my Guide Dr. R. Suganya and Co Guide Dr.
K.R. Premlal for their guidance in each and every step of this venture in completing my Library
dissertation.
I thank Dr. N. Vezhavendhan, M.D.S., Dr. S. Vidyalakshmi, M.D.S., Dr. M. Sivaramakrishnan,
M.D.S., for their support and motivation.
I also thank my friends, and colleagues for their help in completing my Library Dissertation.
Dr. N.S. ARUNGANI
Post Graduate Student
Department of Oral and Maxillofacial Pathology & Oral Microbiology
Indira Gandhi Institute of Dental Sciences, Puducherry.

TABLE OF CONTENTS
S.NO. TITLE PAGE NO
1. INTRODUCTION 1
2. HISTORY OF TOBACCO 3
I. Global history of tobacco
4
II. Indian history of tobacco
8
3. TYPES OF TOBACCO 10
I. Botanical types of tobacco
11
II. Commercial types of tobacco
12
4.
TOBACCO CULTIVATION AND PROCESSING
20
I. Cultivation of tobacco
21
II. Processing of tobacco
26
5. COMPONENTS AND PHARMACOLOGY OF TOBACCO 30
I. Components of tobacco
31
II. Pharmacology of tobacco
6. IMPACT OF TOBACCO 33
I. Impact of tobacco on economy
34
II. Social and environmental consequences
36

7. IMPACT OF TOBACCO IN HEALTH 38
I. Myths on tobacco
39
II. Facts on tobacco
43
8. TOBACCO CONTROL MEASURES 82
I. Global tobacco control measures 83
II. National tobacco control measures in India 94
9 CONCLUSION 99

APPENDIX 1
LIST OF TABLES
S.NO. LEGENDS PAGE NO.
1.
Smoking tobacco - Flue-cured tobacco 22
2.
Smoking Tobacco – Bidi 23
3.
Chewing Tobacco 24
4. Miscellaneous varieties of tobacco
25
5.
Carcinogens in tobacco smoke 47
6.
Carcinogens in certain type of cancer 55
7. Carcinogenic compounds in Smokeless Tobacco
72

APPENDIX 2
LIST OF FIGURES
S.NO. LEGENDS PAGE NO.
1. Tobacco warehouse 7
2. Night riders 7
3.
Quotes of warning from the Night riders
7
4. N. Tabacum 12
5. Roll-Your-Own (RYO) cigarette 16
6. Women smoking large cigar 16
7. Women smoking Cheroot 16
8.
Kretek
16
9.
Pipe smoking
16
10.
Water pipe
16
11.
Betel quid
19
12.
Paan
19
13.
Gutkha
19
14.
Man ingesting Gutkha
19
15.
Gudakhu
20
16.
Khaini
20

17.
Khaini mixed with slaked lime
20
18.
Moist and Dry snuff, Snus
20
19.
Tobacco cultivation
27
20.
Steps in cultivation of tobacco plant
28
21.
Air curing
28
22.
Fire curing
28
23.
Flue curing
28
24.
Sun curing
28
25.
Curing methods of tobacco
29
26.
Steps in processing of tobacco
29
27.
Overview of GTSS
88
28.
MPOWER
90
29.
The 5A’s
93
30.
The 5R’s
93
31.
Benefits of quitting smoking
95
32.
The Pictorial warnings for smoking and smokeless
tobacco
97
33.
The Pictorial warnings for smoking and smokeless
tobacco
97
34.
GATS India
98

35.
No smoking logos in public places
98

APPENDIX 3
ABBREVIATIONS
WHO World Health Organization
ICAR
Indian Council of Agricultural Research
RYO Roll-Your-Own
SLT
Smokeless tobacco
FCV Flue Cured Virginia
CTRI Central tobacco research institute
TS
Tobacco Smoke
PAH Polycyclic Aromatic Hydrocarbons
NNK
4 (Methylnitrosamino)-1-(3-pyridyl)-1-butanone
NNN
N-nitrosonornicotine
VC
Vinyl Chloride
GSTs
Glutathione-S-Transferases
UGTs
Uridine-5′-Diphosphate-Glucuronosyltransferases
NATs
N-acetyl-transferases
ETS
Environmental Tobacco Smoke
COPD
Chronic Obstructive Pulmonary Disease
TB
Tuberculosis

CVD Cardiovascular Diseases
CO
Carbon monoxide
Cd
Cadmium
CHD
Coronary Heart Disease
OPMD Oral Potentially Malignant Disorders
OSCC Oral Squamous Cell Carcinoma
OSMF Oral submucous Fibrosis
FCTC Framework Convention on Tobacco Control
TobReg Tobacco Product Regulation
TFI Tobacco Free Initiative
GTSS Global Tobacco Surveillance System
GYTS Global Youth Tobacco Survey
GATS Global Adult Tobacco Survey
SHS Second Hand Smoking

ABSTRACT:
Tobacco, the plant indigenous to America is now grown across the whole world.
It is the common term, for many plants from Nicotiana genus, nightshade family. There are
70 species of Nicotiana genus recognized, and about 45 of them can be found in India. Earlier
the plant was considered as a God sent remedy as it was used to treat many common
ailments. As time went by the people started to know about its addictive properties and
utilized it in two forms, the smoking and smokeless tobacco. These products have huge
impact on the health, economy, social and environment condition. The WHO and other
organizations have been making policies and programs to increase the awareness of people
about the ill effects of these products and also to help those who are willing to quit this habit.
These programs are adopted by many countries in order to control and regulate the tobacco
related issues. Tobacco causes many harms due to our wrong utilizations. But it is used as a
medicine, in our alternate medicine systems even today. Thus safer proportions gives us
better results. This library dissertation gives an overview about the tobacco and health effects
caused by the tobacco products.

1
The herb, Tobacco holds a long history by facing both the extreme ends of
gloriousness and dreadfulness. Tobacco is the common term, for many plants from Nicotiana
genus, nightshade family. The plant is indigenous to America, and now it is cultivated across
the world. Records states that Christopher Columbus, an Italian, contributed to the spread of
the tobacco plant worldwide. There are 70 species of Nicotiana genus recognised, and about
45 of them can be found in India.
In the olden days it was considered as a God sent remedy for all diseases. It was used
either alone or with mixture of different native herbs, to cure almost all ailments of the
human body, and also for animals. Thus tobacco behaved as a medicine and as a tradition in
the lives of ancient people. As time went by the people started to know its addictive
properties and used it in abusive ways. Both the smoking and smokeless tobacco products
have equal negative effects over the health of humans. Tobacco production has a huge impact
in economy, health and environmental factors.
Papers and books were published about the health warnings of the tobacco products.
But the process of production and consumption of these products continued among the people
from then till now. The WHO and other organisations started to make policies and
programmes to increase awareness among the people about the ill effects of these products.
In all times, there exists confusion regarding the tobacco as a boon or a curse among the
society.
The literature available from these search engines: NCBI Bookshelf, Text books,
books from PDF drive, articles index in Pubmed and a few blogs were used in this library
dissertation. In this review, briefing on the history of tobacco, its types, manufacturing, the
impact of tobacco on economy, social and environment consequences with major discussion
on the impact of tobacco in health is done.

3
I. GLOBAL HISTORY OF TOBACCO:
6000 B.C, 1 B.C
It is believed that Native Americans cultivated tobacco since 6000 B.C and by 1 B.C,
the usage of tobacco skyrocketed among them. The cultivated tobacco was of two species- one
was “Nicotiana rustica” and the other was “Nicotiana tabacum” which were dispersed in
Southern and Northern parts of America, especially in the regions of Andes.(1, 2, 3)
This
indicated the native origin of tobacco, which was also backed by various archaeological,
botanical, anthropological and antiquity records.(1,2)
1400s
The written documentation of tobacco began in the year 1492 by Christopher
Columbus, an Italian who discovered the sailing route to America. He developed the interest
on observing native Americans smoking habits and the way of treating illness with a herb which
he had never seen before. He decided to take those herbs to Europe, thereby initiated the spread
of tobacco worldwide. At the same time, tobacco cultivation started in Cuba followed by
Middle East. (1,4)
1500s
The Chinese cultivated their first plantation of tobacco of in 1530. In 1531, the
cultivation took place in Santo Domingo (America) which was initiated by the European
settlers. (4)
The word Tobacco underwent a variety of pronunciation and spelling changes until
when John Florio published an Italian – English Dictionary “World of Words” in London in
1598 mentioning tobacco as “Nicosiana” (Italian). Nicosiana in English means “The herb
Tobacco”. During this period tobacco got its attention worldwide. It didn’t leave Indian soil as
well. (2)
1600s
From the beginning of 16th century till the end of 19th
century, this plant enjoyed a
widespread reach especially for its medicinal values whose beneficial uses were stated as
almost endless. (1)

4
In 1600s, Tobacco was introduced by Portuguese in India, and had a huge impact in
India. By 1603, tobacco cultivation was well established in Japan and in 1604, in England,
King James I wrote a paper ‘A Counterblaste to Tobacco’ where he highlights the ill effects of
tobacco. In 1612, America started to grow tobacco for commercial purposes whereas in 1633,
Turkey announced death penalty for smoking. At the same time a Chinese philosopher named
Fang Yinhi said that continuous smoking of tobacco for a long period of time shall ‘scorche
one’s lungs’. By the end of 16th
century tobacco usage became a custom among the people of
Europe and it was exported to India, China and Japan.(1,4)
1700s
In England 1761, the first study was made on the effects of tobacco among snuff users
by John Hill and it stated that snuff users had risk of developing nasal cancers. In 1795 Samuel
Thomas Von Soemmering from Germany reported the development of cancer of lip in the pipe
smokers. (4)
1800s
In 1800 Canada grew tobacco commercially. In 1862, the USA devised its Federal
Tobacco Tax to aid in finance for the Civil War. (4)
1900s
An important event at this time took place in the states of US, the Tobacco War
i. The Tobacco War
During the early twentieth century violence started in the tobacco belt of Kentucky
and Tennessee (US) as farmers tried to lessen their economic distress. The buyers of tobacco
had formed a trust called the ‘American Tobacco Trust’ formerly called as Duke Trust, which
was found by James Buchanan Duke in 1890 and were dominating the tobacco market by
simply buying tobacco from small companies and abolished his rivals. By the end of the
century this Duke Trust sold upto 82 % of the tobacco products and became one of the
world’s richest men. In 1900 a farmer could earn from six to eight cents for a pound leaf,
after a few years the price dropped to two to three cents, because of the domination of the
Duke Trust in the market. Due to this the farmers were unable to make a living, banks and
businesses that relied on these farmers went down.(5, 6)

5
On September 1904, Felix Ewing a businessman from Tennessee and Joel addressed a
gathering of about 1,000 farmers and formed an organization to fight against the trust. They
formulated a charter and called it as "The Planters Protective Association". About 5,000 new
members joined the association within a few days. The objective of this Association was to
offer better prices for the crops by pooling them and fixing the prices. (7, 8)
Many farmers refused to join this association as they were paid great prices by the
trust in an attempt to break the association and they were called as ‘hillbillies’ . There was a
great deal of friction between these two groups of farmers. The initial efforts lead by David
Amos, was meant to get more leverage for farmers in opposition to the American Tobacco
Trust, in order to get some economic control over the lives of the farmers. Amos had a tight
focus on the activities, by organizing night raids on tobacco warehouses, in order to show the
strength of local farmers from Kentucky and Tennessee. (5, 8)
Night riding began in an attempt to force the others to come into the farmers
Association. They destroyed hillbillies farming by destroying the seed beds, spraying
kerosene and igniting it sowing the beds with salt. During these events, in the tobacco
warehouse, of a prominent hillbilly planter, the doors where the tobacco was heaped inside
were soaked with kerosene and sticks of dynamite hurled inside. Within moments the
building exploded which was glaring and ear splitting. Thus, making nearly 10,000 men to
join the association. (7)
The then US President Theodore Roosevelt prohibited anti-competitive business
practices and declared Duke Trust as unconstitutional. In 1906, the Association formed with
the official name of "The Silent Brigade". It was a series of events, not a single one and not
an organized response under a single leadership. It was a period where a number of issues
came to occur in Kentucky. The participants in these violence came to be known as the
tobacco night riders. These acts of violence collectively came to be known as the Black Patch
War. The Black Patch referred to the region of the Kentucky and Tennessee which are noted
for the growth of dark-fired tobacco. (6)

6
Figure 1: Tobacco Warehouse
Figure 2: Night riders
Figure 3: Quotes of warning from the Night riders

7
1950
In 1950 Doll and Hill from UK and Wynder and Graham from USA had published their
first major reports on smoking stating that smoking causes lung cancer. In 1962, the British
Royal College of Physicians of London, UK published a Report by on Smoking and its health
effects. In 1964 USA Surgeons General’s Report stated that smoking causes lung cancer in
men. (4)
ii. Tobacco As A Custom
Tobacco is an important plant to Native Americans. The tobacco is used for prayer,
protection and healing. they use tobacco for ceremonies, such as rituals that bless the house
and family. The tobacco is burned around the entire house, and over the family members
inside. (1, 9)
Santo Domingo Tobacco, is traditionally used by priests in rain ceremonies, by mixing
with herbs whose smell are believed to be sacred. This mixture is smoked in a clay pipe or
corn husk (outer membrane of fruit). By blowing smoke, it is believed that the powers that
send the rain is gained. (10)
In US, tobacco was used to as a custom in order to promote the community, spiritual, and
emotional well-being. It was used as an offering to the God, to persons and place. A gift of
tobacco was considered as a sign of respect and was also offered for asking for guidance,
help or protection. In many teachings, the smoke of tobacco was believed to carry thoughts
and prayers to the God. (9)
II. INDIAN HISTORY OF TOBACCO
1500s, 1600s
In India, tobacco was introduced by European travellers, especially by the Portuguese
during the period of Akbar (1550 to 1605). The plant was first cultivated in the state of Gujarat,
followed by Andhra Pradesh before 1600. By 1617, tobacco usage became widespread, even
among the common people. In the Golkonda kingdom (1618 to 1622) much of the tobacco
cultivated was exported to Mocha and Arakan. By 1630 tobacco were exported to about
500,000 pounds and contributed to good revenue to the government.(11)

8
During 1669 to 1679, tobacco was included in the gift items given to the holy men.
On the Coromandel coast tobacco was used to be served with betel leaves and areca nut at all
Hindu weddings. The natives of India smoke tobacco more that their children of age 3 or 4
years frequently intake it, and it is made frequent amongst them.(11)
1700s
In the year 1787, the Royal Botanic Garden was established which is known today as
“Calcutta Botanical Garden”. The garden is one among the oldest gardens in Asia, and was
established by the East India Company, which was mainly planned for the purpose of
increasing the revenue of the company. Other plants such as cardamon, clove, cinnamon, black
and white pepper were also cultivated for commercial purposes.(12, 13)
1900s
In order to endorse and organize agricultural research all over India. A Council was
proposed by the Royal Commission on Agriculture, to guide research activities. In 1903,
‘Imperical Agricultural Research Institute’ was initiated which is presently known as ‘Indian
Council of Agricultural Research’ (ICAR). (13)
The Government of India also established a Tobacco Board in place of “Tobacco Export
Promotion Council” under the Tobacco Board Act of 1975, in order to regulate and facilitate
production and promotion of tobacco in overseas market and control the imbalance between
supply and demand. (13)
2000s
Now, tobacco is one of the important cash crops of India. According to the WHO report,
annual production of Flue Cured tobacco increased in 2017-18 around 239.05 million kg as
against 204.07 million kg produced during previous year. The gross national income per capita
is Rs 1,23,078 per year. Tobacco offers significant employment opportunities to both in-farm
and out-farm situations. The prime beneficiaries of tobacco trading are small and marginal
farmers, rural women and tribal youth.(14)

10
I. BOTANICAL TYPES OF TOBACCO
The genus Nicotiana is one of the genera of Solanaceae, about 70 species are recognised and
are grouped in the following sub-groups: (3, 15, 16, 17, 18)
Nicotiana rustica
Nicotiana tabacum
Nicotiana petunioides
Among the 70 species Nicotiana tabacum and Nicotiana rustica are cultivated the most.
Some of the common species of tobacco are listed below: (15)
Nicotiana alata (Indian tobacco, Flowering tobacco, Ornamental
tobacco, Winged tobacco, Jasmine tobacco)
Nicotiana attenuata (Coyote tobacco)
Nicotiana clevelandii ( Cleveland's tobacco)
Nicotiana excelsior
Nicotiana forgetiana
Nicotiana glauca (Tree tobacco, Glaucous tobacco)
Nicotiana glutinosa
Nicotiana langsdorffii (Langsdorff's tobacco, Fumo-bravo )
Nicotiana longiflora ( Long flower tobacco)
Nicotiana obtusifolia (Desert tobacco)
Nicotiana paniculata
Nicotiana plumbaginifolia (leadwort-leaved tobacco)
Nicotiana quadrivalvis ( Indian tobacco)
Nicotiana repanda (Fiddleleaf tobacco)
Nicotiana rustica ( Aztec tobacco )
Nicotiana suaveolens ( Australian tobacco )
Nicotiana sylvestris ( South American tobacco )
Nicotiana tabacum
Nicotiana tomentosa
Nicotiana velutina ( Velvet tobacco)

11
Figure 4 : N. tabacum
II. COMMERCIAL TYPES OF TOBACCO:
Based on usage tobacco is classified as:
i. Smoking tobacco
ii. Smokeless tobacco
i. Smoking Tobacco:
Smoking tobacco whose usage is characterized by burning of the tobacco, and the smoke that
is created can be inhaled or is held in the mouth. In some regions, ‘reverse smoking’ is
observed, where the burning end is placed inside the mouth.
The following are the different forms of smoking tobacco: (19 - 23)
a. Cigarettes
b. Cigars
c. Cheroots
d. Bidis
e. Kreteks
f. Pipe smoking
g. Water pipes
h. Sticks

12
a. Cigarettes:
The major components include tobacco, filter and paper wrapping. (19)
Cigarettes consist of shredded tobacco leaves processed with chemicals in it. They can be
made with or without filter, the popular most are with filter-tips, which are made by machine
mostly. Another important segment is present which is Roll-Your-Own (RYO) cigarettes, -
hand rolled cigarettes which are also used worldwide. (20)
Cigarettes are available throughout the world and constitutes the predominant form of
tobacco product globally. About 80 % of the global tobacco grown is used for cigarettes. (19)
Electronic Cigarettes:
Also called as Vape Pen, Hookah Pen, e-Hookah
These Electronic Cigarettes often resemble traditional cigarettes but their heat source is
usually by battery, it contains a liquid that holds nicotine and flavourings, this liquid is called
as e-liquid. the battery is turned on to convert the e liquid into aerosol that is inhaled by the
user. (19, 20)
b. Cigars
It comprises of air cured and fermented shredded tobacco particles wrapped in a tobacco leaf
or other wrapping substance, the tobacco wrapper. (19, 20)
It comes in different flavours for attracting younger population, with many sizes and shapes
from smaller ones called as little cigars, or cigarillos to larger ones called as premium cigars,
10 gram cigars are called as double corona cigars. (20, 21, 22)
Regional variations of cigars are the stumpens and cheroots in Western and Central Europe
and dhumtis, which are conical cheroots that are used in India. The larger ones are equally
harmful in producing 10 times the nicotine and 5 times carbon monoxide than a filtered
cigarette. (20, 22)
Cigars are available throughout the world. (19)
Cigars were initially thought to present with comparatively little harm than cigarettes, though
it is a misconception, because it can be as equal as or more harmful than the usual filtered
cigarettes. It is also an illegal product circulating in the market. (19, 20)
c. Cheroots:

13
They are smaller cigars which is made of heavy-bodied tobacco. They are not wrapped by
wrapper rather contain a single binder. (20, 21)
d. Bidis:
They consist of small amounts of tobacco with flavouring agents packed along with it and
wrapped in a non-tobacco leaf which is called as tendu or Tembruni and are tied with small
strings. (19,21)
Bidis are found though out South East Asia, and are more popular in India. Once the sale of
bidis were 8 times than that of the cigarette. In India bidis are hand rolled and manufactured
in small scale cottage industries mostly. (19)
Though they are smaller in size, their carbon monoxide and tar deliveries can be greater than
the manufactured cigarettes due to the need to puff harder to keep bidis lit.
e. Kreteks:
They are also regional products whose origin is in Indonesia and so the popularity. It is a
cigarette like product made of tobacco, cloves, cocoa and other flavouring agents wrapped in
paper. They are mostly clove flavoured, They also contain a wide range of flavourings and
eugenol in it which has an anaesthetising effect, allowing deeper inhalation of smoke. Here it
is mostly manufactured by machine. (19, 21)
f. Pipe smoking:
Pipe smoking is one of the oldest form of smoking. They are smoked around the world but
they differ in size, shape and the material used which include slate, briar, clay or other
substances – the tobacco is kept in the bowl and is inhaled through the stem, sometimes
through water. In Southeast Asia clay pipes are used which are known as chilum ,suipa, and
hookli. (21,22)
g. Water pipes:
Has a lot of names Shisha, Nargeela, Hookah, Narghile, Argileh, Okka, Boury, Hubble-
bubble, Kalian, Argeela, Sheesha, Ghelyoon, Ghalyan and Gouza. (19)
The shisha or hubble bubble, are commonly used in the Mediterranean region, North Africa,
and parts of Asia. (19)

14
The waterpipe works by placing the tobacco product in a bowl with pores in the bottom of it.
The bowl is attached to a tube linked with a water container. The tobacco leaves are heated
by hot charcoal which emits smoke. The water acts as a cooling agent and may actually
increase the harm by enabling water pipe smokers to inhale deeper into the lungs. Inhalation
of this toxic substance for an hour is as equivalent as 100 cigarettes. (14,23,24)
h. Sticks:
They are made from sun-cured tobacco that is known as brus and are wrapped in cigarette
paper. (19)
Types Of Tobacco Smoke:
Tobacco smoke comprises of the following:
➢ Mainstream smoke
➢ Side stream smoke
➢ Mainstream Smoke:
It is the smoke from the smoking tobacco (cigarette, cigar, pipes) that is inhaled by the
smoker. (25)
➢ Side Stream Smoke:
It is the smoke from the smoking tobacco (cigarette, cigar, pipes) along with the surrounding
environmental particles. It is the combination of the smoke that is exhaled by the smoker, the
smoke from the smoking tobacco and surrounding air. (25, 26)

15
Figure 5 : Roll-Your-Own (RYO) cigarette
Figure 6 :Women smoking large cigar, Figure 7: Women smoking Cheroot
Figure 8: Kretek, Figure 9: Pipe smoking
Figure 10: Water pipe

16
ii. Smokeless Tobacco (SLT):
Smokeless tobacco is the tobacco that is consumed without burning.
The main forms of SLT :
a. Chewing tobacco :Betel quid (Paan, Gutkha, Gudakhu, Khaini, Pan masala,
Mawa, Mishri, Zarda, Naswar, Shammah, and Toombak)
b. Snuff: (dry and moist snuff)
c. Dissolvable products
d. Snus
a. Chewing tobacco:
➢ Betel quid:
Betel quid is a form of smokeless tobacco containing betel leaves, slaked lime, areca nut and
tobacco with flavouring agents like cinnamon, cloves. Other forms of quid with a little
variation in composition are Paan, Gutkha, Gudakhu, Khaini, Pan masala, Mawa, Mishri,
Zarda, Naswar, Shammah, and Toombak. (19, 27, 31, 32)
This form is popular in South and South East Asia. (19)
▪ Gudakhu – is a paste of tobacco and sugar molasses mixture. ( 27, 30, 32)
▪ Paan – comprises of betel leaves, areca nut , slaked lime and catechu, tobacco. (19, 21,
27, 30)
▪ Gutkha – made of areca nut pieces coated with powdered tobacco, flavoring agents,
and other ingredients that has the potential to increase the addiction. ( 27, 30)
▪ Khaini- composed of dried tobacco leaves which are crushed and mixed with slaked
lime (27, 31)
▪ Pan masala is a mixture of areca nut, catechu ,slaked lime, and condiments, along
with powdered tobacco. (27, 28, 29, 31)
▪ Mawa is a combination of areca nut pieces, aromatic tobacco, and slaked lime that is
mixed whenever necessary and chewed as a quid. (27-30)
▪ Mishri, are roasted tobacco powder that is used as toothpowder because it is believed
among the people that it has germicidal effects and helps in cleaning the teeth. (29)
▪ Naswar, is a mixture of sun-dried, and powdered local tobacco, flavouring and
colouring agents, slaked lime, ash and oil. The mixture is rolled into balls and is

17
usually placed under the tongue and sucked. It is used widely in Afghanistan,
Pakistan, Iran and the central Asian Republics. (27, 28)
▪ Shammah - a mixture of powdered tobacco, black pepper, lime, ash, oil and
flavouring agents. It is used in the Middle East, Saudi Arabia and Yemen. (28)
▪ Toombak - consists of four parts of tobacco with one part of sodium bicarbonate. It is
primarily used in Sudan. (27, 30)
b. Snuff:
Another form of smokeless tobacco comprising shredded tobacco leaves which are powdered.
There are two Types of snuff:
➢ Dry snuff
➢ Moist snuff
➢ Dry snuff is a mixture of dried tobacco powder and aromatic chemicals. It is inhaled
through the nose and is found to be more common in European countries. (19, 21, 27, 30)
➢ Moist snuff – comprises of Pulverized tobacco, that are fermented and packed. They
are placed between the vestibule, lip or the gingiva and spitted out after a while. This
form of tobacco is popular in US and Scandinavia. (19, 21, 27, 30)
c. Dissolvable products:
It can be attributed as a form of smokeless tobacco, which are sold as lozenges, strips, sticks,
or even may look like a candy with flavourful agents. Its nicotine content can cause
addiction. (19, 21, 27. 28, 29)
d. Snus:
Snus is a finely grinded moist form of non-fermented tobacco product. The snus is available
as packets or pouches. The pouches are placed most commonly in the vestibular region of the
upper lip. They are kept in the mouth for about 15 minutes to 1 hour, after which is disposed,
it is separated from smokeless tobacco list as it need not be spitted. (19, 21,27, 30)

18
Figure 11 : Betel quid
Figure 12: Paan
Figure 13: Gutkha, Figure 14: Man ingesting Gutkha

19
Figure 15: Gudakhu
Figure16: Khaini, Figure 17: Khaini mixed with slaked lime
Figure 18: Moist and Dry snuff, Snus

20
TOBACCO
CULTIVATION AND
PROCESSING

21
I. CULTIVATION OF TOBACCO:
Tobacco seeds are planted in masses, the cultivation of tobacco has to undergo various
processes before it is ready for market.
Due to the different conditions the type of soil, climate, rainfall, irrigation, fertilizers,
pesticides in the diverse tobacco growing locations the tobacco leaves can vary in size, colour
and flavour. Also factors during harvesting, curing, handling and processing influence the
quality of the leaf and ultimately the product manufactured. The quality of the leaf is
determined by its colour, texture, thickness, strength, aroma, flavour and processing qualities.
The Quality is expressed in grades. The US Department of Agriculture (USDA) recognizes
117 levels of grades for tobacco. ( 2, 12, 32, 33, 34)
i. Climate And Soils:
To grow tobacco 15-20 degree Celsius temperature and 50 to 100cm of annual rainfall is
required. Tobacco plants cannot stand if the rainfall is more than 100cm. After harvesting to
drying the leaves, the plant requires dry weather and good sun, but not less than 8%
moisture.(33)
Different types of soil are required for different types of tobacco. Bidi tobacco - alluvial
soils, loamy soils or black clay soil. Cheroot and cigar tobaccos - grey to red soils varying
from light gravelly to sandy loams. (33)
ii. Various Types Of Tobacco Cultivated In India (34)
Table 1: Smoking tobacco - Flue-cured tobacco
S.NO. Variety, Year of release
1. Chatam, 1950
2. Delcrest, 1960
3. Kanakaprabha, 1971
4. Dhanadayi, 1972
5. CTRI Special, 1976
6. 16/104, 1976
7. FCV Special, 1976
8. Jayasri, 1979
9. CTRI Spl. (MR), 1980

22
10. GodavariSpl. , 1982
11. Swarna, 1984
12. Mc Nair 12, 1986
13. Jayasri (MR), 1986
14. Hema, 1987
15. Bhavya, 1988
16. Gauthami, 1992
17. CM 12 (KA), 1993
18. VT 1158, 1993
19. Kanchan, 1998
20. Thrupthi, 1998
21. Rathna, 2001
22. 222, 2012
23. CH-1, 2015
24. N-98, 2015
25. LT Kanchan, 2015
26. CH-3, 2016
27. CTRI Sulakshana (TBST-2), 2018
28. FCJ-11 , FCR-15 2019
Table 2: Smoking Tobacco - Bidi
Sno Variety, Year of release
1. GT 4, 1976
2. NPN 190, 1979
3. Anand 119, 1984
4. Anand 2, 1984
5. Spoorthy (PL 5), 1984
6. GT 5, 1985
7. GT 7, 1993
8. GTH1, 1995
9. Bhavyasree, 1997
10. GT 9, 2001

23
11. MRGTH-1, 2008
12. ABT 10, 2009
13. Vedaganga 1, 2009
14. GABT-11, 2013
15. Nandyala Pogaku-1, 2015
16. NBD-209, 2016
17. ABD-132, 2019
Table 3: Chewing Tobacco
SNo. Variety, Year, Region
1. Chama, 1956, West Bengal
2. Podali, 1956, West Bengal
3. DP 401, 1958, Bihar
4. GandakBahar, 1976, Bihar
5. Sona, 1977, Bihar
6. Vairam, 1977, Tamil Nadu
7. Thangam, 1980, Tamil Nadu
8. Bhagyalakshmi, 1980, Tamil Nadu
9. Maragadham, 1981, Tamil Nadu
10. Prabha, 1981, Bihar
11. PT 76, 1990, Bihar
12. Meenakshi, 1992, Tamil Nadu
13. Vaishali Special, 1993, Bihar
14. Lichchavi, 2001, Bihar
15. Manasi, 2004, West Bengal
16. Abirami, 2006, Tamil Nadu
17. Kaviri, 2006, Tamil Nadu
18. Meenakshi (CR), 2007, Tamil Nadu
19. Sangami, 2008, Tamil Nadu
20. Kamatchi (VDH 3), 2013, Tamil Nadu
21. Abirami (CR), 2013, Tamil Nadu
22. DJ-1, 2013, West Bengal

24
23. BSR-1, 2014, Tamil Nadu
Table 4: Miscellaneous:
SNo Type of tobacco Varieties
1 Hookah and Chewing
(Rustica) tobacco
DD 437, Sonar Motihari, GC 1, GT 6, GCT 2, GT 8, GCT
3, Dharla, Azad Kanchan
2 Motihari tobacco Manasi, Torsa
3 Natu tobacco Prabhat, Vishwanath, Natu Special, Gajapati, Bhairavi
4 Cheroot tobacco DR 1, Bhavani Special, Lanka Special, Sendarapatty
Special
5 Cigar-wrapper
tobacco
S 5, Krishna
6 Burley tobacco Burley 21, Banket A1, HDBRG (Dark burley)
iii. Steps In Tobacco Cultivation:
Generally, tobacco cultivation consists of following process:
a. Raising seed beds:
Since the seeds are very small and fragile, it must be raised in seedbeds before being planted
in the field.
b. Suckering:
As the crop grows the suckers are removed by a process called suckering. The suckers are the
side shoots which grows once the flower of the plant is removed, as they utilize more of water
and minerals from the plants which can lower the quality of the leaves. They can be removed
either by hand or by using chemicals. This process of removing by hand is done at the time of
harvesting or during the earlier stage of growth. (2, 35)
c. Harvesting:

25
As the leaves reach the desired size, they are collected together, and this process is known as
harvesting.
The harvesting time for each types of tobaccos differs in India: (33)
FCV tobacco – December to March in Andhra Pradesh and July to September in Karnataka.
Bidi tobacco - January to February
The cigar and cheroot tobaccos - 90 to 100 days after planting when the leaves become brittle
and yellowish green.
The chewing tobacco – 110 to120 days after planting when the leaves develop puckering
The hookah tobacco (rustica) - May or June, when broad flecks appear on the leaves.
d. Priming:
Certain types of tobacco (Flue cured, oriental tobacco) is harvested in stages as the leaves ripen
and they are not removed all at once. This process is called priming. (35)
I. PROCESSING OF TOBACCO:
After cultivating the plants processing has to be done in order to obtain the final tobacco
product.
i. Curing:
After harvesting or priming curing is done, which is the drying or reducing the moisture content
on the leaves for processing it further. (32, 35)
This curing is of four methods, they are:
a. Air curing
b. Flue curing
c. Fire curing
d. Sun curing
a. Air curing
Air curing is done in barns in which the leaves are stacked in bundles and hung for
curing, natural heat is employed in this type of curing. Air cured tobacco will be brown in
colour. (2, 35)

26
b. Flue curing:
In Flue curing artificial heat is the main source, which is obtained by oil or petroleum. The
curing barns contains pipes for letting in heat and fans dissipate the heat to the entire barn. In
humid conditions artificial heat is required. Curing of unstringed leaves in bulk is termed as
bulk curing done in bulk barn, this type of curing is done in tobaccos that require a great amount
of artificial heat. Here the tobacco is yellow to dark orange in colour which is referred to as
virginia tobacco. (2, 35)
c. Fire curing:
Exposure of tobacco to heat and smoke in open fires is involved in fire curing, here the
smoke alters the taste of the tobacco. (35)
d. Sun curing:
In Sun curing the tobacco leaves are exposed to sunlight. (35)
Figure 19 : Tobacco cultivation

27
Figure 20: Steps in cultivation of tobacco plant
Figure 21: Air curing , Figure 22: Fire curing
Figure 23: Flue curing, Figure 24: Sun curing
ii. Picking:
After curing, picking is done which is the removal of non-tobacco related materials
and undesirable leaves from the tobacco plant. (35)

28
iii. Threshing:
After picking, the blade of the leaves are cut away from the stem with a machine
called thresher, which results in smaller pieces of leaf blade which are suitable to use in
cigarettes. This process is called threshing .(35)
iv. Blending:
Followed by which blending is done, which is mixing of different types of tobacco in
a predetermined ratio in order to obtain a flavourful content. (2)
v. Re Drying And Packing:
Blending is followed by re drying and packing. This tobacco is packed, stored and
transported to various tobacco sellers. (35)
Figure 25: Curing methods of tobacco
Figure 26: Steps in processing of tobacco

29
COMPONENTS AND
PHARMACOLOGY OF
TOBACCO

30
I. COMPONENTS OF TOBACCO:
The World Health Organization in 1981 stated that the leaves of tobacco contain high
amounts of protein, amino acids like lysine, and no nicotine. K.H. Ginzel stated to WHO that
young tobacco plants can yield the most superior plant protein, the Fraction-1-protein (F-1-p)
which is colourless, tasteless, odourless and can be obtained in pure crystalline form from the
plant. The functional characteristics of this protein can be superior to soy protein, animal
proteins from egg white and casein. The protein is said to have an optimal amino acid which
has the ability to lower the cholesterol. (36)
The efficiency of F-1-p was identified superior to soy, corn and casein through
Experiments. It is also said that it can be used for kidney dialysis patients and as artificial
milk for infants. F-2-proteins can also be added to the beverages and is considered to boost
up the nutritional quality. (37, 38)
The Leaf Protein International demonstrated the extraction of crystalline F-1-p in 1981. It
stated that tobacco plants can generate four times more protein per acre as of soybeans and
corn with a yield of F-1-p of 600 kg/ha.(36)
It also stated the nicotine concentration of the
leaves is 20 ppb, which is lower than tomatoes, potatoes or green peppers. (36)
Mendel and Vickery stated that immature seeds of tobacco contained small fractions of
alkaloids. Then nicotine was detected in the sprouts and cotyledons after 9 to 11 days
germination. However the investigators showed later that this has little or no effect on the
nutritive properties of the seed. Lapayette B. Mendel stated that they could not demonstrate
the alkaloid content in tobacco seeds. (39)
Paolo Fantozzi et al in 1983stated that The digestibility of the protein from tobacco was
highest among the vegetable protein sources. He also stated that by using high level of
nitrogen fertilizer and more planting can result in high yields of protein upto 1794 Kg/ha. (40)
M Parameswaran et al in 1988 evaluated the total Protein concentrate of the tobacco
leaves by heat coagulation method in bidi tobacco and demonstrated 52% of protein, which
was free from nicotine. He fed 25% of the dietary protein supplement with this tobacco
protein to the albino rats and observed its growth to be comparable with the control
animals.(41)
Nicotine:

31
Nicotine, an alkaloid is produced by the plants of this nightshade family, though not by
every plant of this family. The species of this family containing traces of nicotine are Atropa
belladonna, Datura stramonium, Duboisia myoporoides and the edible plants like potatoes,
tomatoes, eggplants, Capsicum. The sprouted areas of potatoes contain more nicotine than the
usual amount. Cooking reduces the amount of nicotine by half. The tomatoes contain less
nicotine as they ripen. Nicotine content in the leaves of N. tabacum is 1-3%, N. rustica
contains up to 9% nicotine.
II. PHARMACOLOGY OF TOBACCO:
Nicotine being the main component of significance in tobacco, it is considered here.
Nicotine, acts in a biphasic way: it causes stimulation in low dosage and sedation in high
dosages. In lower concentration, nicotine is said to promote the release of numerous
hormones and nerve transmitters like dopamine, adrenaline, norepinephrine. These further
cause increased heart rate and blood pressure by constricting the blood vessels (especially the
peripheral). (42)
Liver releases glucose for rapid availability to the motor muscles. the blood sugar levels
are increased which may be due to the blocking of insulin, which causes a feeling of satiety
or absence of hunger. Increase in the feeling of sharpness, alertness, may be observed which
are similar to those caused by psychostimulants. If nicotine concentration in blood is higher,
these stimulating effects are short lived and are replaced by sedative and pain-reducing
effects. Anxiety will be reduced and the user experience feeling of relaxation. Dopamine is
increased, creating reward systems in the brain, a cause of addiction. (42)

33
The consequences encountered due to tobacco usage can be broadly categorised as: (42)
I. Economy
II. Environment
III. Health
The impact of tobacco on economy and environment are briefly discussed here. As
tobacco and health is the topic of concern in this library dissertation, Impact on health is
discussed in detail in the next chapter.
I. IMPACT OF TOBACCO ON ECONOMY:
The tobacco smoking not only takes the health of the smoker but also his wealth.
According to WHO, about 5 to 15% of a smokers income is spent on tobacco products, which
can be a huge economic burden on them and their family. (42)
i. Reasons For Producing Tobacco Plants:
a. Tobacco is one among the most economically significant crops in the world.
b. It is drought resistant
c. Takes only a short duration to grow
d. It can be cultivated on soils where other crops cannot be cultivated profitably.
For many decades there was a steady growth in tobacco production but in the 1990s
the world demand for tobacco products came to a pause. Demand from the developed
countries declined, in less developed countries the growth has slowed down. This pause is
due to many facts such as diversification, litigation and consolidation. (32)
Consolidation has prevailed for many years but over ruled in 1990s, due to the slow
demand for tobacco, the small companies were not able to meet the demand, manufacturing
and distributing the products and other marketing processes. This caused merging of the
larger companies with smaller companies so that high volumes of tobacco can be obtained
from fewer locations. The private companies were absorbed by multinational companies.
Thus in 1999s, the companies British American Tobacco (BAT), Philip Morris and China
National Tobacco Corporation (CNTC) dominated the production of global cigarette which
accounts two-thirds of production. These situations had unpleasant effects on the tobacco
suppliers as well as the leaf producers, dealers, machine workers, paper suppliers. (32)

34
In 1990s China produced 30 % of world tobacco. 12 % of the total is occupied by the
United States making it the world’s second largest producer. Other principal suppliers of
tobacco include Japan, Indonesia, Brazil and Germany. (32)
According to WHO in 2000, the production of tobacco globally was nearing 7 million
metric tons, which was more than double the amount of production since 1960s. Tobacco
plant was grown in about 125 countries, the land occupied for cultivation of the species is
over 4 million hectares, one third of this entire land belongs to China. Tobacco accounts less
than 1 % of the global agricultural land. Lands attributed to cultivation belongs to China
majorly then comes the USA, Canada, Mexico, Malawi and United Republic of Tanzania.
Brazil, China, India, Turkey, USA produce about two thirds of the global tobacco. (43)
Other largest producers of tobacco includes Indonesia, Zimbabwe, Zambia, Pakistan,
Argentina (44)
ii. Tobacco Production In India:
In India, tobacco is grown in about 15 states which includes Andhra Pradesh, Assam,
Bihar, Chattishgar, Gujarat, Karnataka, Madhya Pradesh, Maharashtra, Odisha, Tamil Nadu,
Telangana, Uttar Pradesh, West Bengal. The important types of tobacco in India include flue-
cured tobacco, country tobacco, burley, bidi, rustica, hookah, cigar-wrapper, cheroot,
Oriental, HDBRG, burley, Lanka, Pikka, Natu and chewing tobacco. (11, 13, 15, 43 )
Flue Cured Virginia (FCV), Burley and Oriental tobacco account for the major exportable
tobacco types. (13)
India grows N. tabacum extensively in most areas of the country. The N.
tabacum varieties called as desi types are developed for cigarette, cheroot, cigar, bidi, hookah
and snuff tobaccos. (13)
N. rustica requires cool climate, so its cultivation is limited mainly to the north and
north-eastern areas of the country, which includes U.P., Bihar, West Bengal and Assam.
The N. rustica, known as `vilayati' and `calcuttia' are developed for only chewing and snuff
tobaccos. In addition many species of Nicotiana, such as N. affinis, are grown as ornamental
plants.
There are about 70 Nicotiana Sp. available in the world, of which 45 can be found in
India. In the year 2016, India has occupied the second position in tobacco production and in

35
the following year it is pushed to the third position. (44)
In 2017, the leading tobacco producer
is China whose production is about 2.4 million tons, followed by Brazil producing 880.88
tons and then comes India whose production is 799.96 tons[19].
In exports, India ranked 3rd
with Brazil and USA ahead. Tobacco and its products earns about 20,000 Crores and 5000
Crores by foreign exchange. India is the 3rd
largest producer of Flue-Cured Virginia (FCV)
tobacco in the world. In India, production of FCV tobacco is about 240million Kg , which
accounts for around 30% of total tobacco produced in India. (44, 45)
According to Central Tobacco Research Institute (CTRI) 2020 report in India, tobacco
is grown in about 0.45 Million hectares producing approximately 750 Million kg of tobacco
leaves. India being the 3rd
largest producer and exporter globally after China and Brazil. The
production of FCV tobacco is about 300 million kg and non-FCV tobacco 450 million kg. In
the global market, Indian tobacco occupies about 10% of the area for cultivation and 9% of
the total quantity of tobacco production. (43)
It provides employment to 36 million people, including farmers, farm labourers engaged
in tobacco farming, people working in processing, manufacturing and exports. Bidi rolling
provides employment for 4.4 million people and tendu leaf collection is done by 2.2 million
tribes. Annually, tobacco contributes about 4,400/- crores for foreign exchange accounting
4% of the country’s agriculture exports and 14,000 crores to excise revenue which accounts
more than 10% of the total collection from all sources. (46)
During the past five years, exports of tobacco and its products is increased by 76% and
209%. Germany, UK, Belgium, the USSR, South Korea and South Africa are the major
importers of Indian FCV tobacco accounting for about 60% of our exports. (46)
II. SOCIAL AND ENVIRONMENTAL CONSEQUENCES:
Tobacco Smoking affects both the social interaction and relationships. In most of the
cultures, people see smokers in a negative way (like smokers are smelly, disgusting, dirty) . A
smokers personal relationships can be affected, as many people don’t consider being in a
relationship with a smoker. A smoker’s, child is more likely to smoke especially at their
younger age. (42)
i. Types Of Smoking:
a. First hand smoking
b. Second hand smoking

36
c. Third hand smoking
a. First Hand Smoking:
First hand smoking is the mainstream smoke that is inhaled by the smoker. The one
involved in this type of smoking is the smoker himself.
b. Second Hand Smoking:
It is the combination of both the mainstream and side stream smoke. If people inhale this
smoke then it is termed as passive smoking which is also called as involuntary smoking. Non-
smokers are more likely to experience this type of smoking. Though ignored, this type of
smoking is as harmful as first hand smoking. (25, 26, 47)
c. Third Hand Smoking:
Third hand smoke refers to the second hand smoke residues that gets deposited in the
skin surfaces and objects, furniture others where a smoker lives. Infants, children’s are more
prone to this type of smoking as they meddle with objects and place it in mouths. The effects
of third hand smoking is not well recognised and is being studied. (47)
Burning of the tobacco produces a number of toxicants in the environment. The greater
use of fertilisers, pesticides and mechanisation, that contributed to the production of higher
yields are environmentally damaging. This problem doesn’t end with the growing tobacco,
the processes in curing the leaves can cause massive deforestation. Manufacturing, packing
and transportation of these products also cause environmental pollution. (42, 43)

37
IMPACT OF TOBACCO
IN HEALTH

38
I. MYTHS ON TOBACCO:
The tobacco plant was used as an orthodox medicine by the medical professionals.
Friar Ramon Pane, a Catalan priest on his journey observed and stated that in India the
powder was used by the medicine man to be grabbed with joy, after which he used to perform
a ritual for the sick men, by blowing on his temples, forehead and neck, and then declaring
that he had drawn out the sickness of the patient. (1)
Amerigo Vespucci, the Florentine navigator, wrote on his voyage to the New World in
1499, that he saw Indians on island of Margarita chewing leaves of a herb mixed with
pulverized lime to relieve thirst. (1)
Tobacco was considered to be the “God-sent remedy”. (1)
Tobacco were used in different
forms with different ingredients in different part of the world for curing different diseases and
its symptoms. It was believed that tobacco has properties of antispasmodic, antiseptic,
narcotic, emetic, anti-diarrhoeic, emollients and anticonvulsant. Fernando Ocaranza wrote
that in 1519 the Indians were using tobacco as medicines for anti-diarrhoeic, narcotics, and
emollients. (1, 48)
In India, the leaves of tobacco was used in traditional medicine as a sedative,
antispasmodic, vermifuge, antiseptic, narcotic and emetic. In Malaysia, dried tobacco leaves
infusion was taken as sedative. (1, 48)
The traditional medicinal uses are as follows:
i. Respiratory disorders
ii. Gastrointestinal disorders
iii. Reproductive disorders
iv. Dermatological disorders
v. Infection and wounds
vi. Urinary system disorders
vii. Miscellaneous

39
i. Respiratory disorders
Monardes N. in 1571 and Wateson G. in 1598 described that finely grounded tobacco and
snuff, was used as a remedy for colds. (49)
Antonio De Herrera Y Tordisillas, a Spanish
historiographer, in his writing from 1601 to 1615 said that the tabaco cures pain caused by
cold, in smoke form it was beneficial against colds, asthma and coughs. It was described that
the powdered tobacco was used along the nasal passages to clear out the passage, they used to
place a cane which was one foot long the one end was at the nostril and through the other end
the powder was placed. (1)
In Egypt the Dried leaves and flowers were smoked to relieve asthma. In Fiji fresh roots
are taken orally for Asthma. In India, fresh leaves are mixed with cob of corn or
Amorphophallaus paenoifolium (the Elephant Yam) to treat asthma. (48)
In Haiti dried leaves decoction was taken orally for bronchitis and pneumonia . In Peru,
the Jivaros, used the tobacco juice to treat pulmonary ailments. In Ecuador, the leaf juice was
used to treat of pulmonary ailments. (48)
ii. Gastrointestinal Disorders:
Alonso Niffo in 1500 reported it to be used as a dentifrice. In United States the Native
Americans, mixed with lime or chalk and used it as a toothpaste to whiten the teeth. In India,
powdered tobacco, was massaged on the teeth for this purpose and tobacco toothpaste was
marketed commercially. (1, 48, 49)
In Guatemala, extract of dried leaf with hot water are applied externally for stomatitis. In
Asia, chewing tobacco was recommended for toothache and gum diseases, throat aches. In
India, exudate from the stems and leaves are used in cases of gingival inflammation. In
Nicaragua leaves of tobacco was chewed for tooth ache. In Fiji, the seeds are taken orally for
treating hoarseness of voice. (48)
When babies suffer from stomach problems, the herb black wool, tobacco and the nest of
Cacicus chrysopterus, Icteridae, Aves (Birds) were fumigated around the cradle and anus of
the baby. In Brazil the leaf juice was taken orally to induce vomiting & narcosis.In Papua
New Guinea, the tender leaves were chewed to relieve stomach ache. In Fiji, fresh roots of
the plant are taken orally for indigestion. (48)

40
In India, tobacco was traditionally used to treat strangulated hernia. In Asian countries,
decanted liquor of tobacco which was boiled, were used internally for treating indigestion,
aches in the belly. (48)
iii. Reproductive Disorders:
In Cuba, the extract of leaves was taken orally to treat the dysmenorrhea. In Mexico,
extract of the tobacco plant was massaged on the abdomen with saliva which was used to
ease the expulsion of placenta. In Tanzania, the leaves are placed in vaginal region to
stimulate labour. (48)
In Asia, tobacco with honey was used to treat syphilis. In Papua New Guinea, decoction of
tender leaves was taken orally for treating gonorrhoea. (48)
The inhabitants of Surguna in
Madhya Pradesh apply warmed leaves on testis to treat hydrocele.
iv. Neurologic Diseases:
In 1490s, in India the tobacco was used to prevent fatigue. (1)
In Fiji, fresh root juice was
applied for bloodshot eyes. In Kenya, water extracts are applied for corneal opacities and
conjunctivitis. (48)
Monardes N. in 1571 and Wateson G. in 1598 described that finely
grounded tobacco and snuff, was used as a remedy for headache and eye problems. (49)
In
Nigeria, for the treatment of convulsions, leaves were crushed and juice was collected which
was used as a bath in water. (48)
In Asian countries tobacco juice into the ears has said to improved deafness. In United
States, the extract of the plants was taken orally to treat tiredness. In Asian countries smoking
tobacco was claimed to improve body odour. Indians and Negroes powdered it in their
mouths in order to fall asleep and feel no pain. (48)
v. Dermatological Disorders:
In India, tobacco was traditionally used to treat skin diseases. In Colombia, crushed leaves
with palm oil was used to prevent baldness. In Iran, ointments made from crushed leaves
were used to treat baldness, dermatitis and Pediculicide. In Peru, the Tikiana men used to mix
the palm oil with crushed leaves as a hair dressing to prevent hair loss. In Papua New Guinea,
dried plants were mixed with bark of Gaibulima belgraveana (white magnolia) & Zingiber
officinale (ginger) and was taken orally for lice. (48)

41
In Nepal, tobacco leaf juice was applied externally to treat scabies. Ointment made with a
mixture of ashes of tobacco with pig fat were applied to ulcerated skin, warts, dermal cancer.
vi. Infection And Wounds:
In Colombia, Poultice was prepared from fresh leaves and was used over boils, infected
wounds. In Turkey, the leaves are powdered and was applied externally for wounds. In
Mexico the tobacco leaves are applied for pain relief, used in powdered form for the relief of
catarrh and applied locally to heal wounds and burns. In Guatemala, the leaves are applied
externally for wounds and extract of dried leaf with hot water are applied externally for
ringworms, bruises sores, wounds and ulcers. (48)
In Egypt the dried leaves and flowers are burned and smoked to relieve influenza.In India
juice of Securinega leucopyrus was mixed with dried tobacco leaves and was applied
externally for parasitic infections. In East Africa, dried leaves and Securinega virosa are
mixed and used externally to destroy worms in sores. (48)
In Peru, the Jivaros use the tobacco juice for snake bite. In Nepal, hot water extract of
dried flower and leaves are used externally for snake and spider bite. In Argentina, tobacco
was applied for snake bites with milk and oil. (48)
vii. Urinary System Disorders:
In Guatemala, the leaves were taken orally for kidney diseases. In Asian countries,
decanted liquor of tobacco which was boiled, were used internally for treating urinary tract
obstruction. Tobacco Smoke (TS) into the ear was used to cure ear ache and when applied to
the anus, it relieved constipation and bloody discharge.
viii. Miscellaneous
In Egypt, tobacco leaves are used as a poultice along with oil to treat rheumatic pain. In
India Decoction of leaves was applied for muscle relaxation, also used to relieve pain and
swelling associated with rheumatic conditions. In Fiji, the seeds are taken orally for treating
rheumatism. (48)
The Portuguese used smoke and the tobacco in cases of fistulas, ulcerated abscesses, sores,
uncurable polyps. The Tukanoan peoples rub a decoction of leaves over sprains and bruises.
Pedro Alvarez Cabral, a Portuguese nobleman reported the herb for treating fistulas,
ulcerated abscesses, sores, uncurable polyps and other ailments. (49)
In Nepal, application of

42
leaves were used for pain; tobacco was used in powder form to relieve catarrhal conditions;
and was applied locally to heal wounds and burns. In China the people of Lop Nur use
Apocynum venetum ( sword-leaf dogbane plant) with the tobacco as the leaves of Apocynum
venetum was believed to have low tar content and hence used as an agent to detoxify the
nicotine content.
In 1490s, tobacco herb was used by the Indians as disinfectant. In Brazil, dried leaves
are used as an insecticide. Tobacco was also used to treat distemper, a viral infection in
animals with cooking oil and milk. Onion, lemon, and tobacco mixture with white soap and
warm water were used to treat scabies. (48)
II. FACTS ON TOBACCO:
As time went, it was recognized that tobacco was not a cure for all ailments. In 1601,
anonymous pamphlet were released, in London. This pamphlet described that tobacco was a
poison and stated that tobacco was harmful because it deprives the body nourishment, dries
up men’s sperm, and had a stupefying effect. This pamphlet also added that tobacco should
be avoided especially by young people and pregnant women . (49)
In 1604, King James I, England stated a warning that smoking was injurious to the brain,
eyes, nose, and lungs. In 1620, Thomas Venner, London wrote that excessive use of tobacco
harms the brain and sight, diminishes digestion, and induces palpitation, shaking of the limbs.
He said that tobacco should be limited to medicinal use and not for pleasure. After which
many reports were established regarding other diseases caused by tobacco. And despite the
warnings about the possible harms that tobacco may induce on its abusers, it took nearly 450
years to distinguish the consequences of tobacco usage. (49)
Tobacco Abuse
The tobacco products contain about 5000 toxic substances in it. (42)
Among which the most
important and dangerous constituents are:
➢ Nicotine
➢ Carbon Monoxide
➢ Tar
➢ Carbon dioxide
➢ Nitrogen oxides
➢ Hydrogen cyanide

43
➢ Ammonia
➢ Volatile nitrosamines
➢ Volatile hydrocarbons,
➢ Volatile sulfur containing compounds
➢ Aldehydes
➢ Ketones
➢ Nicotine:
Nicotine is an important and major cause of behavioural effects of the tobacco. It is a
poisonous substance that leads to addiction of the user. It influences and reinforces the
tobacco use behaviour. After absorption, nicotine reaches the brain rapidly (in seconds) and
hence, the smoker gets this psycho active rewards very quickly within seconds of smoking.
This nicotine binds to receptors in the brain thereby influencing the cerebral metabolism. It is
then distributed throughout the body, especially to the skeletal muscles. (42)
It has a structure similar to the neuro-transmitter acetylcholine (Ach) that conveys
information from one neuron to the other. The Ach is an important neurotransmitter, that is
involved in systems that concerns with learning and memory, mental and physical arousal,
and other aspects of emotions. The Ach receptors throughout the body that respond to
nicotine are called as nicotine receptors . The nicotine thus combines with Ach receptors and
exerts actions like Ach at all the areas where nicotine acetylcholine-receptors are present and
can trigger impulses. (42)
ii. Health Effects Of Smoking Tobacco
Tobacco is deadly in any form. Tobacco smoking is the leading cause for premature
death of approximately 6 million people worldwide (Action on Smoking and Health, 2016;
World Health Organization, 2013). The premature death due to smoking is deﬁned as a form
of death, in an individual due to a smoking-related disease otherwise whose death would have
later been for another cause. Globally, over 22 000 people die from tobacco use or second
hand smoke exposure every day and one person is lost for every 4 seconds states the WHO
2019. (25)
Smoking tobacco products, contains about 7000 chemicals, at least 250 chemicals are
known Some among these compounds can cause cancers of various organs in the body. It is

44
found that the smokers who does not stop smoking lose 10 years of an average of life
expectancy when compared with non-smokers and they suffer diseases around 10 years
earlier than non-smokers (Jha & Peto, 2014). Smokers, after the age of 40 have a higher
levels of pain and disability than non-smokers (US Department of Health and Human
Services, 2004). (50)
Another entity apart from the conventional cigarettes is the cigar, it has been found
that more young adults, especially females are attracted to cigar due to their flavour and
lesser cost. When compared to cigarettes. People also think that cigar is less harmful than
conventional cigarettes due to the fact that they need not inhale the smoke from cigar. Studies
state that cigars are equally as harmful as cigarettes. In cigars the concentration of nitrogen
oxide, ammonia, carbon monoxide and tar are higher than in cigarettes. It also contains
nicotine in content equivalent to cigarettes, and are capable of producing dependence of
nicotine or addiction. Tobacco affects almost all organs of the human body. (25, 50, 51)
Some of the systemic health effects of smoking tobacco are depicted below:
a. Malignancy
b. Respiratory diseases
c. Cardiovascular diseases
d. Endocrine disorders
e. Gastrointestinal disorders
f. Reproductive disorders
g. Immunologic diseases
h. Neurologic diseases
i. Dermatological diseases
a. Malignancy:
Benowitz et al in 2010 stated that smoking is the largest preventable cause for cancer,
accounting approximately 30% of the deaths due to cancer. Tobacco smoking has been
proven to cause cancers of the lung, larynx, oral cavity, pharynx, oesophagus, pancreas,
bladder, kidney, cervix, and stomach, colorectal and liver cancers, and acute myeloid
leukaemia. (25, 51)
The Tobacco Smoke (TS) contains more than seventy types of carcinogens (Leon et al.
2015; Established list 2012). Tobacco fumes are flooded with carcinogens namely 4

45
(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosonornicotine (NNN), 1-
Hydroxypyrene, benzo(a)pyrene, 4-Nitroquinoline 1-oxide (4NQO) and nicotine (Hecht
2003). Tobacco and its smoke contain radioactive elements like 210Pb, 210Po, 226Ra, 228Ra
and 40K, capable of getting assimilated in cells of oral mucosa and organs like kidney,
respiratory tract and spleen (Savidou et al. 2006; Papastefanou 2009; Nagamatsu et al. 2011).
Conjointly, tobacco and its smoke contain heavy metal ions like iron, copper, and chromium,
nickel, lead, cadmium, mercury, arsenic, and antimony ions (Bagchi 1997). The heavy metal
ions catalyze the generation of reactive oxygen species which induce cellular damages in the
exposed tissue structures (Bagchi 1997). (51, 52)
➢ Carcinogens In Tobacco Smoke:
International Agency for Research on Cancer has listed the carcinogens, which are as follows
Table 5: Carcinogens in tobacco smoke
S.NO. Carcinogen Quantity (per cigarette)
Polycyclic aromatic hydrocarbons
1. Benz[a]anthracene 20–70 ng
2. Benzo[b]fluoranthene 4–22 ng
3. Benzo[j]fluoranthene 6–21 ng
4. Benzo[k]fluoranthene 6–12 ng
5. Benzo[a]pyrene 8.5–17.6 ng
6. Dibenz[a,h]anthracene 4 ng
7. Dibenzo[a,i]pyrene 1.7–3.2 ng
8. Dibenzo[a,e]pyrene Present
9. Indeno[1,2,3-cd]pyrene 4–20 ng
10. 5-methylchrysene ND–0.6 ng
Heterocyclic compounds
11. Furan 20–40 μg
12. Dibenz[a,h]acridine ND–0.1 ng
13. Dibenz[a,j]acridine ND–10 ng
14. Dibenzo[c,g]carbazole ND–0.7 ng
15. Benzo[b]furan Present
N-nitrosamines

46
16. N-nitrosodimethylamine 0.1–180 ng
17. N-nitrosoethylmethylamine ND–13 ng
18. N-nitrosodiethylamine ND–25 ng
19. N-nitrosopyrrolidine 1.5–110 ng
20. N-nitrosopiperidine ND–9 ng
21. N-nitrosodiethanolamine ND–36 ng
22. N’-nitrosonornicotine 154–196 ng
23. 4-(methylnitrosamino)-1-(3-pyridyl)
1-butanone
110–133 ng
Aromatic amines
24. 2-toluidine 30–200 ng
25. 2,6-dimethylaniline 4–50 ng
26. 2-naphthylamine 1–22 ng
27. 4-aminobiphenyl 2–5 ng
Heterocyclic aromatic amines
28. 2-amino-9H-pyrido[2,3-b]indole 25–260 ng
29. 2-amino-3-methyl-9H-pyrido[2,3-b]indole 2–37 ng
30. 2-amino-3-methylimidazo[4,5-f]quinoline 0.3 ng
31. 3-amino-1,4-dimethyl-5H-pyrido [4,3-b]indole 0.3–0.5 ng
32. 3-amino-1-methyl-5H-pyrido[4,3-b]indole 0.8–1.1 ng
33. 2-amino-6-methylpyrido[1,2-a:3′, 2′-d]imidazole 0.37–0.89 ng
34. 2-aminodipyrido[1,2-a:3′,2′-d]imidazole 0.25–0.88 ng
35. 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine 11–23 ng
Aldehydes
36. Formaldehyde 10.3–25 μg
37. Acetaldehyde 770–864 μg
Phenolic compounds
38. Catechol 59–81 μg
39. Caffeic acid <3 μg
Volatile hydrocarbons
40. 1,3-butadiene 20–40 μg
41. Isoprene 450–1,000 μg

47
Some of the strongest of carcinogens such as Polycyclic Aromatic Hydrocarbons
(PAHs), N-nitrosamines, and aromatic amines, occurs in low amount, some of the weaker
carcinogens, such as acetaldehyde and isoprene, occur in the higher amounts. Hence a simple
addition of these of the carcinogenic agents can be misleading. (51)
PAHs are incomplete products of combustion which was first identified as
constituents of coal tar (Phillips 1983). This product occur as a mixture in tar, grilled foods,
soot, automobile engine exhaust, and others that are generated by incomplete combustion
42. Benzene 12–50 μg
Nitrohydrocarbons
43. Nitromethane 0.5–0.6 μg
44. 2-nitropropane 0.7–1.2 ng
45. Nitrobenzene 25 μg
Miscellaneous organic compounds
46. Acetamide 38–56 μg
47. Acrylamide Present
48. Acrylonitrile 3–15 μg
49. Vinyl chloride 11–15 ng
50. 1,1-dimethylhydrazine Present
51. Ethylene oxide 7 μg
52. Propylene oxide 0–100 ng
53. Urethane 20–38 ng
Metals and inorganic compounds
54. Arsenic 40–120 ng
55. Beryllium 0.5 ng
56. Nickel ND–600 ng
57. Chromium (hexavalent) 4–70 ng
58. Cadmium 41–62 ng
59. Cobalt 0.13–0.20 ng
60. Lead (inorganic) 34–85 ng
61. Hydrazine 24–43 ng
62. Radioisotope polonium-210 0.03–1.0 picocurie

48
(IARC 1983). Generally, they are carcinogens which act locally. Some of them like
benzo[a]pyrene (B[a]P) – a PAH, constitute a powerful carcinogenic activity. (51)
N-nitrosamines are a larger class of carcinogens whose activity is demonstrated in at
least 30 animal species (Preussmann and Stewart 1984). They act as systemic carcinogens
that affect different tissues depending on the structure involved. The most common N-
nitrosamines are N’-nitrosonornicotine (NNN) and the tobacco-specific 4-
(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (Hecht and Hoffmann 1988) because
most of the commercial tobacco products contain these together, whose formation occurs
mainly during the curing step of tobacco production. high concentration of NNN and NNK
can be due to the midrib (central vein of the leaves) of Burley air-cured tobacco or the leaf
blade of flue-cured tobacco, or due to the retention of tobacco leaves under humid conditions
or in bales (cubes of tobacco tied together). These processes can encourage bacterial growth,
leading to increased nitrite content, and heating with propane during curing. Indirect fire
methods were used instead of direct-fire , and the levels of NNK and NNN in cigarette
tobacco were examined. Reduction of about 65–78% of NNN and 60–85% in NNK levels
were observed (Rickert et al., 2008).(51, 52)
Yuan et al in 2009 conducted studies on the relationship of NNK with lung cancer in
smokers and stated that metabolites of NNK has a significant association with the risk of
developing lung cancer in a dose-dependent manner. NNK has consistently caused tumours
in mice, rats, hamsters and tumour of nasal cavity in rats and mink. NNN has caused tumours
of the oesophagus in rats, and nasal cavity in multiple species. NNN and NNK in
combination can cause tumours of oral cavity in rats and nasal cavity in mink. (52)
Aromatic amines in the smoke are products of combustion which includes 2-
naphthylamine and 4- aminobiphenyl (4-ABP), which were characterized as human
carcinogens based on exposures related to the dye industry (Luch 2005). Heterocyclic
aromatic amines are again combustion products which are known for their occurrence in
grilled foods (Sugimura 1995), but is also seen in cigarette smoke. (51)
Other carcinogenic compounds in the cigarette smoke includes the human carcinogens
Vinyl Chloride (VC) in lesser amounts and ethylene oxide in limited quantities (IARC
1979).(51)
Though VC is seen more commonly in PVC industries, and is thought to be
associated with occupationally hazardous category, it is also seen in TS. VC in the TS of the
cigarettes accounts about 1.3-16 mg/cigarette and of small cigars 14 to 27 mg/ cigar. The

49
filter cigarettes reduce VC in TS. Animal studies suggest VC to be a multisite carcinogen. In
humans VC is said to contribute to Haemangiosarcoma of liver, malignancy of brain, lung,
lymphatic and haematopoietic system. (53)
Ethylene oxide is linked with malignancies of the hematopoietic and lymphatic systems
(IARC 1994). Various metals such as the cadmium, which is a carcinogen are also present in
cigarette smoke. (51)
➢ Events Related To Tobacco Smoking In Carcinogenesis:
Oral cavity, is a complex organ, that forms the initial part of the gastrointestinal tract and
continuous with the oropharynx, pharynx, oesophagus, stomach, small intestine, large
intestine and the anus . It favours the initial steps of digestion comprising of chewing, mixing
of saliva with food in the mastication process. The saliva which is secreted from salivary
glands, maintains optimal levels of moisture and pH (6.7 to 7.3) in the mouth and also
lubricates the movement of food into oesophagus and stomach. The salivary enzymes
additionally participate in the initial phase of digestion. The oral cavity is continuously in
contact with the tobacco fumes when a person is smoking. (54)
Most carcinogens in the cigarette smoke requires the metabolic activation which are
generally catalysed by cytochrome P-450 enzymes. These enzymes converts the carcinogen
to forms which can covalently bind to DNA and form DNA adducts. P-450s 1A1 and 1B1,
are inducible by cigarette smoke by interaction with the aryl hydrocarbon receptor and are
especially important in the metabolic activation of Polycyclic Aromatic Hydrocarbons
(PAHs). (51, 54)
Cancer susceptibility is determined by the metabolic activation and
detoxification process.
Detoxifying Enzymes: Most cigarette smoke carcinogens require a metabolic activation
process, generally catalysed by detoxifying enzymes, to convert them to electrophilic entities
that can covalently bind to DNA, forming DNA adducts. (55)
A number of enzyme families are important in both the activation and detoxification of
carcinogens in cigarette smoke. Some of them are:
▪ Cytochrome P-450s
▪ Glutathione-S-Transferases (GSTs)
▪ Uridine-5′-Diphosphate-Glucuronosyltransferases (UGTs)
▪ N-acetyl-transferases (NATs)

50
▪ Cytochrome P-450s which are encoded by CYP genes, they are microsomal enzymes
that catalyse the oxidation of myriad chemicals, including many of the carcinogens in
cigarette smoke. Shimada et al in 2004 stated that the PAHs are metabolized by P-450
1A1, 1B1. Kim and Guengerich in 2005 stated that aromatic amines are metabolized by
P-450 1A2 and Yoo et al in 1988 stated that N nitrosamines are metabolised by P-450s
2A6, 2A13, and 2E1. (51)
▪ Glutathione-S-Transferases (GSTs) are the other enzymes that detoxifies the epoxides in
conjugation with glutathione. The reaction is catalysed by cytosolic GSTs. The
members of GST class includes GSTA1-1, GSTM1-1, GSTP1-1, and GSTT1-1. Hayes
et al in 2005 stated that polymorphisms in genes that encode these subunits especially in
smokers with cancer risk. Jernstrom et al in 1996 stated that GSTA1-1, GSTM1-1, and
GSTP1-1 catalyse glutathione conjugation of PAHs. Norppa et al. 1995 stated that
GSTM1-1 and GSTT1-1 play an important role in conjugation of two 1,3-butadiene
epoxide metabolites. Brown et al. 1996 stated that Ethylene oxide is also detoxified by
the same. (51)
▪ Uridine-5′-Diphosphate-Glucuronosyltransferases (UGTs) a number of carcinogens in
tobacco smoke Conjugate with glucuronic acid (Bock 1991, Nagar and Remmel 2006).
The metabolites of PAHs (phenol and diol) are eliminated as glucuronide conjugate
(Bock 1991). Carmella et al in 2002 and Bock in 1991 stated that glucuronidation plays
an important role in excretion of NNK metabolites in smokers and also in benzene
detoxification. (51)
▪ N-acetyl-transferases (NATs), epoxide hydrolases, and sulfotransferases are other
detoxifying systems. The balance between carcinogen metabolic activation and
detoxification varies among individuals and is likely to affect cancer susceptibility with
those having higher activation and lower detoxification capacity being at highest risk.
(51, 54)
The balance between the metabolic activation and detoxification varies from person to
person. Person with higher metabolic activation and lower detoxification rate are at a higher
risk from smoking-related cancers. Thus metabolic activation results in formation of DNA
adducts. (54, 55)
DNA Adducts:

51
DNA bases may serve as reactive side branches which can covalently associate with
carcinogenic components and form unnatural DNA structures called as DNA adducts [54]
Numerous studies have evaluated DNA adduct formation in foetuses and in various tissues
and fluids of smokers, including samples from the larynx, oral and nasal mucosa, bladder,
cervix, breast, pancreas, stomach, placenta, and cardiovascular system, and samples of
sputum, sperm, and blood cells. (55)
Some carcinogens does not undergo metabolic activation to form adducts, they
directly enter this step. Thus higher the DNA adducts, the more chances of developing
cancer. Continuous formation of DNA adducts can cause miscoding during replication of
DNA when DNA polymerase enzymes process the adducts incorrectly. Thus gene mutations
has the ability to cause loss of normal functions in controlling of cellular growth via a
complex signal transduction pathway ultimately resulting in genomic instability, cellular
proliferation and cancer. The protective apoptosis can counterbalance these mutations by
removing the cells whose DNA are damaged. The mechanisms that lead to apoptosis and
those mechanisms that suppresses the apoptosis also has a major impact on tumor growth. (55)
The following is the pathway for cancer causation in cigarette smoking:

52
Figure 28 : Pathway of cancer causation in cigarette smoking
Evidence Of DNA Adducts - Micronuclei:
The exfoliated buccal cells of the smokers show a higher number of micronuclei, the
extra-nuclear structures, located in cytosol, that is formed during the metaphase to anaphase
transition of the basal cells during cell cycle. The presence of micronuclei is indicative of
daughter cells with genomic complement deficiency in the genetic information.
Micronuclei may contain mis-segregated chromosomes or broken fragments of
chromosome (Bhat et al. 2015). Sabharwal et al in 2015 stated that micronuclei formation
acts as a biomarker for abnormalities in of nucleus and chromosome that is induced in oral
epithelium by the genotoxins. The TS induces DNA breakages, and cancer cells are more
susceptible to the DNA damages than the healthy cells. (55, 56)
Apoptosis:
Apoptosis, or programmed cell death, which is a protective process that removes the
cells with DNA damage and counterbalance the mutational events. Martin in 2002 states that

53
apoptosis is a critical event for eliminating injured unstable cells thereby minimizing damage
to the surrounding normal cells. Rich et al in 2000 stated that induction of apoptotic process
prevent the growth of cancer cells. The balance between the mechanisms leading to apoptosis
and suppressing apoptosis has a major impact on cancer progression. (56)
Cellular Repair System:
The Cellular repair systems has the ability to remove DNA adducts and turn the
structure of the malformed DNA to a normal one. When these repair enzymes are overloaded
by DNA damage, they cannot function efficiently which results in persistence of DNA
adducts which can lead to a higher chance of developing cancer. (57)
The cellular repair enzymes include:
▪ DNA polymerase
▪ DNA ligase
The DNA polymerase is the enzyme which synthesizes DNA by fixing the nucleotides
together. The DNA ligase is the enzyme that are involved in joining the ends of the strands of
the DNA together with the covalent bond in order to make a continuous DNA strand. The
sequential action of both these enzymes is required for formation of normal DNA. (57)
The following are the list of carcinogens involved in certain cancers:
Table 6: Carcinogens in certain type of cancer
S.No. Type Of
Cancer
Carcinogen Involved
1. Lung Polycyclic Aromatic Hydrocarbons, N-nitrosamines 4-
(methylnitrosamino)-1-(3-pyridyl)-1-butanone, ethyl carbamate,
isoprene, ethylene oxide, benzene, aldehydes
2. Larynx Polycyclic Aromatic Hydrocarbons
3. Oral cavity Polycyclic Aromatic Hydrocarbons, N-nitrosamines 4-
(methylnitrosamino)-1-(3-pyridyl)-1-butanone, N-nitrosonornicotine
4. Esophagus N-nitrosonornicotine, other N-nitrosamines
5. Cervix Polycyclic Aromatic Hydrocarbons, N-nitrosamines 4-
(methylnitrosamino)-1-(3-pyridyl)-1-butanone

54
6. Liver N-nitrosamines 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone,
other N-nitrosamines
7. Pancreas N-nitrosamines 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone
8. Leukemia Benzene
➢ Malignancy Of Respiratory Tract
▪ Lung Cancer:
Lung cancer is the dominant malignancy caused by smoking. According to WHO, 2019
the total number of cases is estimated to be 1.2 million annually, with about 90% attributed to
smoking. (25)
The strongest determinant of lung cancer in smokers is duration of smoking, the
risk also increases with the number of cigarettes smoked. Smoking increases the risk of all
histologic types of lung cancer: squamous cell carcinoma, small cell carcinoma,
adenocarcinoma (including bronchiolar– alveolar carcinoma) and large cell carcinoma. (55)
Smokers are up to 22 times more likely to develop lung cancer in their lifetime than non-
smokers. Cigar and/or pipe smoking are causally associated with lung cancer. Those who
smoke ﬁve or more cigars per day has the risk of dying from lung cancer 23 times more when
compared with a non-smoker. Another study stated that the risk of lung cancer mortality has
been increased to five folds for men who smoke cigar. (58, 59)
Mayer stated that the risk of
developing lung cancer in cigar smokers is five times higher than non-smokers. Lung cancer
rates, have been shown to be inversely related to vitamin A intake. Pastorino et al. have
previously shown that vitamin A protects against lung cancers related to tobacco smoking.
Cigarette smoking is the most strongly active risk factor in female lung cancer. (57, 58)
▪ Laryngeal Cancer:
Laryngeal cancer is caused by cigarette smoking, and the risk increases with duration of
smoking and number of cigarettes smoked. Risk is greatly enhanced by alcohol consumption
and decreases upon cessation. National Cancer Institute states that there is a six fold increase
in risk for developing laryngeal cancer for those who smoke one or more cigars per day than
a non-smoker. (55, 57 - 59)
➢ Malignancy Of Gastrointestinal Tract:
▪ Oral Cancer:

55
Based on numerous studies, cigarette smokers have risks of oral cancer two to five times
than that of non-smokers . The risks increase with the numbers of cigarettes smoked (53)
and
years smoked and the risk decreases with smoking cessation.(57)
Heavy smokers who drink
alcohol heavily have many times the risk of oral cancer as that expected from the independent
effects of smoking and alcohol intake.(53, 57)
Cigar smokers are seven to ten times more likely
to develop oral cancer than non-smokers. (58)
The pH of cigar smoke is more than cigarettes
making the nicotine content absorbed readily by the oral mucosa, as cigar smoke is not
inhaled mostly by the smokers, the nicotine content does not enter the lung directly, instead it
is absorbed in the oral mucosa . The saliva also contains nicotine content which when
swallowed causes cancer in the oral mucosa and oesophagus. (55)
Garrote et al stated that
cigar smokers are equally prone to oral cancer as cigarette smoker. (59)
In some studies it was
shown that 10 years after quitting, former smokers have the same risk of oral cancer as
people who never smoked, whereas other studies show that the risk decreases dramatically
but remains at a level somewhat higher than that found in people who never smoked. (25)
The
pipe smokers had a 2.0 to 3.5-fold increased risk of developing oral cancer compared to
persons who did not smoke.(25)
75 to 90% of all cases are explained by the combined effect of smoking and alcohol use.
This could be because alcohol dissolves certain carcinogenic compounds in tobacco smoke
and alcohol increases the permeability of the oral epithelium.(54, 60)
The alcohol alone
increases the risk of cancer in the upper aerodigestive tract. Smoking when combined with
alcohol consumption of more than 80g, or more than five to six drinks per day is said to
increase the risk of developing cancers (Pöschl and Seitz 2004).(60, 61, 62)
Although several
mechanisms were proposed suggesting the role of alcohol in oral carcinogenesis, the exact
mechanism is not well understood. Ethanol in the alcoholic beverages is metabolized into
acetaldehyde, a known carcinogen. In addition, PAHs and nitrosamines (carcinogens) may be
present in some of alcoholic beverages. Nutritional deficiencies along with heavy
consumption of alcohol may contribute to carcinogenesis. (62)
▪ Pharyngeal Cancer:
Cigarette smoking increases the risk of sinonasal and nasopharyngeal cancer. It is a cause
of oropharyngeal and hypopharyngeal cancer and the risk increases with duration of smoking
and daily cigarette consumption and decreases with time since quitting. (51, 55)
Cigar smokers

56
have a 4–10 times greater risk of dying from laryngeal, oral, and oesophageal cancers as
compared with non-smokers. (58)
▪ Oesophageal Cancer:
Cigarette smoking causes cancer of the oesophagus, particularly squamous cell cancer. It
is also a cause of adenocarcinoma of the oesophagus, which has been increasing. The risk for
oesophageal cancer is related to duration of smoking and number of cigarettes smoked per
day and remains elevated after cessation. Cigar smokers has two fold increased mortality rate
for oesophageal cancer than non-smokers states a study. Another study from cancer
prevention stated a 4 to 5 fold increase in mortality rate from oesophageal cancer. (51)
➢ Breast And Cervical Cancer:
Studies have demonstrated a link between tobacco smoking and an increased risk of breast
cancer, particularly among heavy smokers and women who start smoking before their first
pregnancy. Smoking is also known to increase the risk of cervical cancer in women infected
with human papillomavirus. The risk of these cancers typically increases with intensity and
duration of smoking, because of the continued exposure to toxins and carcinogens. Cigarette
smoking is a cause of cervical squamous cell carcinoma. (25)
➢ Others:
Cigarette smoking is a cause of developing liver cancer, independent of the effects of
hepatitis B and C infection and alcohol consumption. (57)
Another study stated that cigar
smoking is associated with pancreatic cancer. Smokers are at a significantly higher risk of
developing acute myeloid leukaemia. (51)
Cancer of the nasal and paranasal sinus cavities,
kidney, liver, pancreatic cancers and cancer of the lower urinary tract that includes the
bladder, ureter and renal pelvis). (25)
Pitard et al stated that cigar smoking has risk for
developing bladder cancer than cigarette smokers. (58)
b. Respiratory Diseases:
According to World Health Organization in 2019, about 40% of all the tobacco related
deaths are due to lung diseases like chronic respiratory diseases, cancer and tuberculosis.
Every year about at least 8 million people are killed by tobacco due to respiratory diseases.
(25, 63)
➢ Chronic Obstructive Pulmonary Disease (COPD):

57
According to WHO, one in five tobacco smokers will develop (COPD) in their lifetime,
especially people who start smoking during their childhood, TS significantly slows lung
growth and development. Smokers are 3–4 times at a higher risk for developing COPD than
non-smokers. Adults who were exposed to second hand smoking as children and had frequent
lower respiratory infections as a result, are also at risk of developing COPD. (25)
Tobacco smoking causes rupturing of the air sacs in the lungs thereby reducing the
capacity of lungs to take in oxygen and expel carbon dioxide. It can also cause accumulation
of purulent mucus, resulting in a painful cough and severe breathing difficulties. (25)
Many studies stated that smoking decreases the surfactant activity of bronchoalveolar
lavage fluid. Some studies state that inhalation of cigarette smoke causes decrease in the level
of lung surfactant phosphatidylcholine but others reported no difference in lung lavage
phospholipid concentration between smokers and non-smokers. Thus the findings indicate the
variable effects of cigarette smoke on surfactant and surfactant-producing cells. (64, 65)
Non-smokers exposed to Environmental Tobacco Smoke (ETS) has changes in lung
function. An epidemiological study conducted in Europe comprising 7882 adults revealed
that passive smoking is associated with nocturnal breathlessness, nocturnal chest tightness,
breathlessness after periods of activity, and increased bronchial responsiveness, the smoke
impairs the airway epithelial cells to support repair processes, it can also contribute to
alterations in airway structures . Although cigarette smoking is strongly associated with the
development of COPD, the effects of exposure to ETS on COPD are controversial. Cigar
smokers also have a direct relationship with COPD. They have higher mortality rate than
non-smokers, and are 1.336 times at risk to die from COPD than non-smokers. (59, 64, 65)
➢ Asthma:
Asthma is one among the common respiratory diseases. It is a chronic inflammatory
disease of the airway, which can be due to hyperresponsiveness to specific triggers that can
lead to wheezing, chest tightness, dyspnoea. (66)
Smoking exacerbates asthma in adults, requiring emergency health care. (25)
Active
smoking appears to be an important risk factor for asthma, it plays detrimental effects on the
airway epithelium and smooth muscles, which may worsen outcomes with regard to both
changes in lung function and mortality due to asthma. There is a causal relationship between
parental smoking and the development of asthma in children. Larsson ML et al in 2001

58
conducted a study in Sweden to examine if exposure to Environmental Tobacco Smoke
(ETS) during childhood has impact over asthma prevalence in adults, and to identify the
problems from ETS in which he concluded that Childhood exposure to ETS was related to an
increased prevalence of asthma among adult non-smokers, and some are also more likely to
become smokers. ETS was also found to be a major irritant of lower airway. A systematic
review and meta-analysis conducted by Silvestri M et al concluded that maternal smoking
during prenatal period aids in induction of asthma and wheezing in the offspring, especially
in the first years of life. In a 15-year follow-up of African–American women the incidence of
onset of asthma was increased by, 40% among smokers and 20% among passive smokers
when compared with women of no tobacco exposure. (66, 67)
➢ Tuberculosis (TB):
More than 20% of global incidence of TB is due to smoking. Smoking is a greater risk
factor for TB, independent of socioeconomic status and alcohol consumption.
Tuberculosis damages the lungs, decreases the lung function, which is further exacerbated
by smoking, and increases the risk of death from respiratory failure. According to WHO, one
quarter of the entire world’s population possesses latent tuberculosis, thereby increasing the
risk of developing active disease. Smoking not only doubles the risk of latent tuberculosis
state to an active state, it also worsens the progression of the disease. The WHO also stated
that smokers are twice likely to fall ill with TB. (25, 68)
Factors that contribute to increased susceptibility to develop TB, are defects in immune
cells and altered immune response due to smoking. Mechanical disruption of cilia function
also is considered to appear secondarily due to smoking . It is stated that TB Itself can lead to
chronic respiratory disease, especially bronchiectasis and COPD. According to WHO active
TB cases along with tobacco smoking substantially increases the risk of disability and death
from respiratory failure. (68, 69, 70)
➢ Other Respiratory Illnesses And Reduced Lung Function:
Tobacco smoking has the ability to cause pneumonia and all major respiratory symptoms,
which includes coughing, phlegm and wheezing. Lung function and growth are more likely to
be compromised among smokers. The children of smoking parents suffer similar respiratory
symptoms and lower levels of lung function in their entire childhood. (25)
c. Cardiovascular Diseases (CVD)

59
Cardiovascular diseases are the most common diseases elicited due to tobacco smoking,
followed by respiratory and other system involvement (Action on Smoking and Health,
2016)[30,70]. According to WHO 2019, tobacco use and second hand smoking are the major
contributors, causing about 3 million cardiovascular deaths globally every year. (25)
Another
WHO report from India, 2018 stated that, 48% of the total tobacco death is due to
cardiovascular diseases. This CVDs are more likely to occur in younger individuals from 30
to 44 years of age. 16% of the total CVDs is caused by tobacco smoking. (71)
Smokers have
up to twice the risk of stroke and a fourfold increased risk of heart disease. Those who smoke
just one cigarette per day are already half as likely as those who smoke 20 per day to develop
heart disease and stroke. (25)
It is said that the free radicals generated by smoke are inhaled, hence there is an increased
levels of reactive oxygen species derivatives generated in the lung of the smokers by
phagocytes, which could in turn enter into the circulation and thereby cause cardiovascular
problems (71, 72)
Chemicals in the TS that is inhaled causes the cells that line the blood vessels to become
swollen and inflamed. This can narrow the vessel walls and can lead to many cardiovascular
conditions which includes the following manifestations – endothelial dysfunction,
inflammation, altered lipid metabolism, increased demand for myocardial oxygen, insulin
resistance.
The constituents of TS that has received greatest attention as potential factors that can
contribute to CVD are nicotine, carbon monoxide (CO), and oxidant gas. Some researchers
also state that PAHs, and other particulate matters of the TS are involved in the
pathophysiology of CVD (Brook et al in 2004; Bhatnagar 2006). (72)
Nicotine is a sympathomimetic drug which releases catecholamines systemically from the
adrenal gland and locally from the neurons. Pharmacodynamic studies of nicotine indicate
that though tolerance to effect of nicotine develop rapidly, the tolerance is incomplete
(Porchet et al in 1987). Benowitz et al in 1982 conducted a study with constant intravenous
infusion of nicotine and found that the nicotine increased the heart rate even when their level
in the blood was relatively low, and as the infusion continued, the Heart Rate (HR) reached a
plateau in spite of a progressive rise in blood levels of the nicotine . This same phenomenon
was observed in HR with level of blood nicotine during cigarette smoking throughout the day
(Benowitz et al in 1984). (72)

60
CO is another major constituent of TS. The CO binds readily to the haemoglobin, thereby
reducing the haemoglobin content available to carry oxygen and impeding release of oxygen
by haemoglobin. Studies conducted by Calverley et al in 1981 by Allred et al in 1989 stated
that inhalation of CO in smokers decreased exercise tolerance in patients with angina pectoris
and intermittent claudication. De Bias et al in 1976 stated that inhalation of CO reduces the
threshold for ventricular fibrillation in animals. Benowitz in 2003 stated that long term
exposure to CO in smokers resulted in increased red blood cell mass and decreased oxygen
carrying capacity of the red blood cells, resulting in hypoxemia. In response to hypoxemia,
the red blood cell masses increase in order to maintain the amount of oxygen required by the
organs in the body. The increase in red blood cell mass further increases the blood viscosity
and can contribute to hypercoagulation in the smokers. (72, 73)
TS carries out a greater level of oxidizing chemicals to smokers, which includes oxides of
nitrogen and free radicals (Church et al 1985). Exposure to oxidant chemicals in the TS is
associated with the depletion of antioxidants, which is manifested as reduced levels of
vitamin C in the blood of the smokers than in non-smokers (Lykkesfeldt et al in 2000).
Smoking was also reported to increase lipid peroxidation products levels in the plasma and
urine of the smokers (Morrow et al in 1995). Studies also indicate that oxidant stress
contributes to many potential mechanisms including inflammation, endothelial dysfunction,
lipid abnormalities, and platelet activation (Burke and FitzGerald 2003). (71)
Endothelial dysfunction: Nicotine, free radicals in smoke, oxidants from the TS, free
radicals produced by the endothelial cells themselves in response to TS, decrease the
availability of nitric oxide. Hence, there is no response to stress or vasoconstriction is
encountered (U.S. Department of Health and Human Services 2014; Barua et al 2001; Ichiki
et al 1996). Vasoconstriction, in turn, increases the prothrombotic response. TS induced
damage to endothelium alters the interaction with flowing blood cells, thereby causing the
inflammatory substances and platelets to stick to the vessel wall.
This further decreases the ability of endothelium to regulate local levels of clot formation
and clot dissolving substances (U.S. Department of Health and Human Services 2014; Nowak
et al 1987). Smoking reduces elasticity of the arteries, which results in stiffening of the walls
and thereby reducing the coronary flow reserve (Celermajer et al 1993; Stefanadis et al
1997).

61
Other components implicated in endothelial dysfunction, include the heavy metals such as
arsenic, lead, and mercury, they are involved to catalyse the oxidation reaction of the cellular
proteins. (73)
Bernhard et al in 2005 stated that TS contains a number of metals, including
▪ Aluminium
▪ Cadmium
▪ Copper
▪ Lead
▪ Nickel
▪ Mercury
▪ Zinc
These metals catalyse oxidation reaction of the cellular proteins. This reaction may lead to
cellular damage structurally and also endothelial dysfunction, and separation of endothelial
cells from the vessel walls. Mixture of both the metals and oxidant may be involved in
damaging the endothelial cells. (72, 73)
The effects of smoking on endothelium occurs early, studies suggest that exposure of about
one hour or less to TS, results in endothelial damage which can be long lasting (Juonala et al
2012). And cessation of smoking is also associated with improved endothelial function
(Johnson et al 2010).
➢ Metal Contents In Cigarette:
▪ Aluminium:
Aluminium is greatly concentrated in the cigarettes, whose values ranging from 699–
1200mg/g. It also has role in the development of microcytic anaemia and osteomalacia and
has the potential for inﬂammatory and oxidative events. (74)
▪ Cadmium:
The main source of cadmium (Cd) in humans is through cigarette, the average Cd content
per cigarette is between 0.5 and 1.5mg. When smoking of the cigarette is done, the Cd is
transformed into cadmium oxide, which is then inhaled by the person. Satarug et al reported
that smokers have a 1.7 fold increase of serum Cd content compared to non-smoker. Mortada
et al. reported that the mean blood Cd content in the smokers was 1.9 times higher than non-

62
smokers. Barany et al. found that the serum Cd values of smokers was at least 3.1 fold
higher in comparison to non-smokers. Cadmium levels are higher in serum of smokers, and
cadmium accumulates in the aortic walls of smokers (Abu-Hayyeh et al. 2001).(74)
Epidemiologic evidence indicates an association between serum levels of cadmium and lead
and CVD, including hypertension and MI (AbuHayyeh et al. 2001). (73)
▪ Copper:
The Cu content in the tobacco leaves was said to be 156 mg/g. Serum concentrations in
the smokers who smoke for more than 10 cigarettes per day accounts 0.95 mg/l in youngsters,
1.10 mg/l and 1.31 mg/l in adults. Lapenna et al in 1995 suggested correlation between Cu
levels in plasma and lipid peroxidation in the smokers. (74)
▪ Lead:
The Pb content per cigarette is around 1.2mg, about 6% of the content passes to the
mainstream smoke, which is inhaled by the smokers. the blood brain barrier is quite
impermeable for Pb, the children are especially at high risk to accumulate the Pb in the brain
and central nervous system, which can result in mental retardation. Other health
consequences associated with accumulation of lead are peripheral arterial diseases and
hypertension. (74)
▪ Nickel:
Nickel has been shown to cause a number of diﬀerent forms of cancer, especially of the
respiratory tract. The main mechanism responsible for this activity is that Ni is mutagenic and
has been reported to induce sister chromatid exchanges. Evidence suggest that Ni affects
development of heart in unborn mice. Ni content in the tobacco plant accounts for about 0.64
and 1.15 mg/g, and varies in cigarettes from 0.078 mg to 5 mg. Serum levels of Ni were
analysed, and said that smoking is not an important source for Ni. (74)
➢ Coronary Heart Disease:
Coronary heart disease occurs when arteries that carry blood gets narrowed by either
accumulation of plaque in the vessel wall or formation of clot. (71)
Smoking be a major risk
factor for development of CHD other risk factors include diabetes mellitus, hypertension and
hyperlipidemia. (74)
A meta-analysis stated that smoking by one cigarette per day conveys
around 40-50% of the excess risk for developing coronary heart disease, which is the same as

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