Current medical management of the Acute Radiation Syndromes (ARS) does not include immune prophylaxis based on the Antiradiation Vaccine. Existing principles for the treatment of acute radiation syndromes are based on the replacement and supportive therapy. Haemotopoietic cell transplantation is recomended as an important method of treatment of a Haemopoietic form of the ARS. Though in the different hospitals and institutions, 31 pa-tients with a haemopoietic form have previously undergone transplantation with stem cells, in all cases(100%) the transplantants were rejected. Lethality rate was 87%.(N.Daniak et al. 2005). Conclusion: Specific antibodies – possible antagonists of Toll like receptors and can inhibit massive activation of lysosomal hydrolytic enzymes and prevent radiation toxicity after high doses of Radiation.

1. Molecular
mechanisms of
radiation damage.DMITRI POPOV. PHD, RADIOBIOLOGY.
MD (RUSSIA)
ADVANCED MEDICAL TECHNOLOGY AND SYSTEMS INC. CANADA.

2. Molecular mechanisms of Acute
Radiation Disease.
 DOI: 10.13140/RG.2.1.4687.7924

3. Molecular mechanisms of acute
and chronic radiation damage.
 Lysosomes, lysosomal enzymes and are known to be involved in
radiation induced damage of DNA and cancer develop processes.
The lysosomes contain proteins and enzymes that would constitute
pathways for the hydrolysis of proteins and peptides and DNA
damage and mutations.
 However, integrated biochemical and cell biology studies are
necessary to understand how lysosomal enzymes combined with
oxidant processes could initiate radiation damage and malignant
consequences after irradiation.
 Med Hypotheses. 2005;64(6):1170-2.
 Lysosomal and prostasomal hydrolytic enzymes and redox
processes and initiation of prostate cancer.
 Tappel A1.

4. Radiation Toxins.
 Protease and phosphatase inhibitors are essential components of
most cell lysis and protein extraction procedures.
 These inhibitors block or inactivate endogenous proteolytic and
phospholytic enzymes that are released from subcellular
compartments during cells lysis and would otherwise degrade
proteins of interest and their activation states.
 https://www.thermofisher.com/ca/en/home/life-science/protein-
biology/protein-biology-learning-center/protein-biology-resource-
library/pierce-protein-methods/protease-phosphatase-
inhibitors.html

5. Radiation Toxins. Molecular
Mechanisms of Radiation.
 Lysosomes are membrane-bound vesicles that contain digestive
enzymes, such as glycosidases, proteases and sulfatases.
 Lysosomal enzymes are synthesized in the endoplasmic reticulum
(ER), are transported to the Golgi apparatus, and are tagged for
lysosomes by the addition of mannose-6-phosphate label.
 https://www.google.ca/webhp?sourceid=chrome-
instant&ion=1&espv=2&ie=UTF-8#q=lysosomal%20enzymes

6. Radiation Toxins. Molecular
Mechanisms of Radiation.
 All living organisms contain proteolytic enzymes (proteases and
peptidases).
 In whole cells, protease and phosphatase activities are tightly regulated
by compartmentalization or inhibitors to prevent indiscriminate damage
to cellular proteins and to maintain proper function of signaling
pathways.
 Cell lysis disturbs the carefully controlled cellular environment, allowing
proteases and phosphatases to become unregulated. The usual
consequence of this unregulated state is reduced recovery of total
protein.
 https://www.thermofisher.com/ca/en/home/life-science/protein-
biology/protein-biology-learning-center/protein-biology-resource-
library/pierce-protein-methods/protease-phosphatase-inhibitors.html

7. Radiation Toxins. Molecular
Mechanisms of radiation damage.
 Lysosomes are cytoplasmic membrane-enclosed organelles
containing hydrolytic enzymes that degrade macromolecules and
cell components.
 Lysosomes contain many different hydrolytic enzymes, including
proteases, lipases, nucleases, glycosidases, phospholipases,
phosphatases, and sulfatases, which usually exert maximal
enzymatic activity at low pH.

8. Radiation Toxins. Molecular mechanisms
of Acute Radiation Disease.
 Several degradation pathways converge at the level of the
lysosome, including endocytosis, phagocytosis, and autophagy.
 Lysosomal Function and Dysfunction: Mechanism and Disease
Patricia Boya. ANTIOXIDANTS & REDOX SIGNALING Volume 17,
Number 5, 2012 ª Mary Ann Liebert, Inc. DOI: 10.1089/ars.2011.4405
 Pathological degradation pathways initiated after moderate and
high doses of radiation.
http://www.intechopen.com/books/current-topics-in-ionizing-
radiation-research/radiation-toxins-molecular-mechanisms-of-
toxicity-and-radiomimetic-properties-

9. Radiation Toxins. Molecular Mechanisms
of Acute Radiation Disease.
 The mechanisms involved in radiation-induced cellular injury and death remain
incompletely understood. In addition to the direct formation of highly reactive
hydroxyl radicals (HO*) by radiolysis of water, oxidative stress events in the
cytoplasm due to formation of H2O2 may also be important. Since the major
pool of low-mass redox-active intracellular iron seems to reside within lysosomes,
arising from the continuous intralysosomal autophagocytotic degradation of
ferruginous materials, formation of H2O2 inside and outside these organelles
may cause lysosomal labilization with release to the cytosol of lytic enzymes
 Radiation-induced cell death: Importance of lysosomal destabilization.
Hans Lennart Persson
 University Hospital Linköping Division of Pulmonary Medicine, Faculty of Health
Sciences, University of Linköping, S581 85 Linköping, Sweden.
 Biochemical Journal (Impact Factor: 4.78). 09/2005; 389(Pt 3):877-84.
DOI: 10.1042/BJ20050271Source: PubMed

10. Radiation Toxins and Molecular Mechanisms of
Acute Radiation Disease.
 It is increasingly recognised that IR-induced effects are not limited to
the induction of nuclear DNA damage, but that a number of
intracellular targets, such as lysosomes, can also be affected after
exposure. The lysosome contains enzymes capable of catalysing the
breakdown of intracellular material including DNA, lipids and protein
 Evidence of a role for radiation-induced lysosomal damage in non-
targeted effects: an experimental and theoretical analysis Scott
Bright1 , Alexander G. Fletcher2 , David Fell1 , Munira A. Kadhim1,* 1
Department of Biological and Medical Sciences, Oxford Brookes
University, Oxford, OX3 0BP, UK 2 Mathematical Institute, University of
Oxford, Andrew Wiles Building, Radcliffe Observatory Quarter,
Woodstock Road, Oxford OX2 6GG, UK

11. Radiation Toxins and Molecular Mechanisms of Acute
Radiation Disease.
 The invertase inhibitory protein isolated from Cyphomandra
betacea Sendt and Solanum tuberosum inhibited the
invertase activity from different species, genera and even
plant family. Furthermore, proteinaceous inhibitors are not
invertase specific; fungal, bacterial and higher plant enzymes
including polygalacturonase, pectinase, pectin lyase, alpha-
L-arabinofuranosidase and beta-glucosidase are also shown
to be inhibited.
 J Enzyme Inhib Med Chem. 2002 Feb;17(1):37-43.
 Inhibition of hydrolytic enzyme activities and plant pathogen growth by
invertase inhibitors.
 Isla MI1, Ordóñez RM, Moreno MI, Sampietro AR, Vattuone MA.

12. Radiation Toxins and Molecular Mechanisms of Acute
Radiation Disease.
 Antipain is clearly the most effective of the protease inhibitors
 studied here at suppressing radiation transformation. Antipain
 appears to inhibit all 3 phases of the transformation process,
 presumably reflecting an ability to inhibit more than one pro
 tease involved in this transformation system. It
[CANCER RESEARCH 41, 2103-2108, June 1981]
 0008-5472/81 /0041-OOOOS02.00
 Effects of Protease Inhibitors on Radiation Transformation in Vitro1
 Ann R. Kennedy2 and John B. Little
 Laboratory of Radiobiology, Harvard University School of Public Health.
Boston, Massachusetts 02115

13. Radiation Toxins and Molecular Mechanisms of Acute
Radiation Disease.
 Troll, W., Meyn, M. S., and Rossman, T. G. Mechanisms of protease
action in carcinogenesis. In: T. J. Slaga, A. Sivak, and R. K. Boutwell
(eds.),
 Carcinogenesis, Vol. 2, pp. 301-312. New York: Raven Press. 1978.
 Troll, W., Rossman, T., Katz. J.. Levitz. M., and Sugimura. T. Proteinases
in
 tumor promotion and hormone action. Cold Spring Harbor Conf.
Cell Proliferation, 2. 977-987, 1975.

14. Radiation Toxins and Molecular Mechanisms of Acute
Radiation Disease.
 Kennedy, A. R., and Little, J. B. Protease inhibitors suppress radiation
induced malignant transformation in vitro. Nature (Lond.) 276. 825-
826, 1978.

15. Radiation Toxins and Molecular Mechanisms of
Acute Radiation Disease.
 Antiradiation Vaccine: Immunological neutralization of Radiation
Toxins at Acute Radiation Syndromes.
 http://adsabs.harvard.edu/abs/2010cosp...38.3183P
 Current medical management of the Acute Radiation Syndromes
(ARS) does not include immune prophylaxis based on the
Antiradiation Vaccine. Existing principles for the treatment of acute
radiation syndromes are based on the replacement and supportive
therapy. Haemotopoietic cell transplantation is recomended as an
important method of treatment of a Haemopoietic form of the ARS.
Though in the different hospitals and institutions, 31 pa-tients with a
haemopoietic form have previously undergone transplantation with
stem cells, in all cases(100%) the transplantants were rejected.
Lethality rate was 87%.(N.Daniak et al. 2005).

16. Radiation Toxins and Molecular Mechanisms of Acute
Radiation Disease.
 A large amount of biological substances or antigens isolated from
bacterias (flagellin and derivates), plants, different types of venom
(honeybees, scorpions, snakes) have been studied.
 This biological active substances can produce a nonspecific
stimulation of immune system of mammals and protect against of
mild doses of irradiation.
 But their ( exclude rattle snake venom) radioprotection efficacy
against high doses of radiation were not sufficient.
 http://adsabs.harvard.edu/abs/2010cosp...38.3183P

17. Radiation Toxins.
 The Blocking Antiradiation Antibodies induce an immunologically specific effect
and inhibiting effects on radiation induced neuro-toxicity, vascular-toxicity,
gastrointestinal toxcity, hematopoietic toxicity. Antiradiation Antibodies prevent
the radiation induced cytolysis of selected groups of cells that are sensitive to
radiation. The Blocking Antiradiation Antibodies are immunologically specific
and can be produced by immunization with the different radiation toxins
isolated from irradiated mam-mals. We propose that Specific Antiradiation
Antibodies targeted against the radiation induced Toxins. Specific Antiradiation
Antibodies neutralize toxic properties of radiation toxins. Anti-radiation
Antibodies in different phases of the Acute Radiation Syndromes can compete
with cytotoxic lymphocytes and prevent cytolysis mediated by cytotoxic
lymphocytes. Conclusions: Immunological inhibition of cytotoxic and neurotoxic
properties of Specific Radiation Toxins are significant factors for improving results
of Medical Management of severe forms of the ARS and will optimize results of
traditional methods of therapy of the ARS. Immunological inhi-bition of Radiation
Toxins must be a part of technical procedure before haemotopoietic stem cells
transplantation. Positive therapeutic results of neutralization of SRD RT could
make a procedure of haemopoietic stem cell transplantation efffective.

18. Radiation Toxins and Molecular Mechanisms of Acute
Radiation Disease.
 Journal of Radiation Research, 2013, 54, 243–250
 doi: 10.1093/jrr/rrs098 Advance Access Publication 26 October 2012
 Anti-radiation damage effect of polyethylenimine as a toll-like
receptor 5 targeted agonist.
 Polyethylenimine is a new human TLR5 agonist with potential
application in radiation protection, including, but not limited to,
offering protection for cancer patients who receive radiotherapy or
radiosurgery, and could serve as a new compound for protecting
the health and safety of people in radiation-related accidents.
 Zhiqiang HU1,2, † , Yaling XING1, † , Yuanyu QIAN3, † , Xiaojuan
CHEN1, Jian TU4, Lening REN1,2, Kai WANG1 and Zhongbin CHEN1,*

19. Radiation Toxins and Molecular Mechanisms of Acute
Radiation Disease.
 http://www.slideshare.net/dlpopov/medical-management-of-
acute-radiation-syndromes-comparison-of-antiradiation-vaccine-
and-antioxidants-radioprotection-potency
 http://www.slideshare.net/dlpopov/radiation-vs-rattle-snakebite
 http://www.slideshare.net/dlpopov/rad-toxhydrolyticenzymes
 http://www.slideshare.net/dlpopov/radiation-toxicity-tolllike-
receptors

20. Radiation Toxins and Molecular Mechanisms of Acute
Radiation Disease.
 Conclusion: Specific antibodies – possible antagonists of Toll like
receptors and can inhibit massive activation of lysosomal hydrolytic
enzymes and prevent radiation toxicity after high doses of
Radiation.