Genotoxic stress occurs when chemical agents damage genetic information within cells, causing mutations directly or indirectly through DNA damage. Cells have defense mechanisms that form a complex signal transduction network in response to genotoxic stress. This network activates transcription factors that regulate genes for DNA repair, cell cycle arrest, and apoptosis. Exposure to certain chemicals has been linked to various human cancers by causing genotoxic mutations. To cope with DNA damage from genotoxic stresses such as chemicals, radiation, and normal cell metabolism, cells have developed DNA repair and cell cycle regulation responses that are important for preventing carcinogenesis when altered.

1. Genotoxic Stress Response
In genetics, genotoxicity describes the property of chemical agents that damage the
genetic information within a cell causing mutations(Genotoxicity is often confused
with mutagenicity. All mutagens are genotoxic, whereas not all genotoxic substances
are mutagenic.). The alteration can have direct or indirect effects on the DNA: the
induction of mutations, mistimed event activation, and direct DNA damage resulting
in mutations. Of course, there are exist several important defense mechanisms to
response genotoxic stress. These responses are expected to be very complex,
involving various cellular factors that form an extensive signal transduction network.
This network includes a protein kinase cascade that connects the detection of DNA
damage to the activation of transcription factors, which in turn regulate the
expression of genes implicated in DNA repair, cell cycle arrest and programmed cell
death (apoptosis). What's worse is heritable changes can affect either somatic cells
of the organism or germ cells to be passed on to future generations. Cells prevent
expression of the genotoxic mutation by either DNA repair or apoptosis, so the
damage may not always be fixed leading to mutagenesis.
It has long been acknowledged that exposure to certain chemicals is associated with
the development of human cancers. For example, this linkage has been made
between aflatoxins and liver cancer, amine dyes and bladder cancer, benzene and
leukemia, vinyl chloride and hepatic cancer and smoking and lung cancer. To date,
many human carcinogens have been identified, most of which are categorized as
genotoxic agents, meaning that these chemicals target DNA and produce alterations
in the genetic material of the host. Such environmental agents are only one source of
genotoxic stress, with other sources including UV and ionizing irradiation (IR),
therapeutic agents and the products of normal metabolism. As a result, human cells
are constantly exposed to a variety of genotoxic stresses. To cope with the resulting
damage to cellular DNA, cells have developed a repertoire of responses that ensure
the normal growth and survival of the organism. A logical consequence, therefore, is
that alterations in these responses may be the basis for carcinogenesis. For this
reason, a better understanding of cellular responses to genotoxic stress is important
in the prevention and treatment of human cancers.