Cancer cells avoid apoptosis and continue to multiply in an unregulated manner (B)
Genotoxic Chemotherapy is the treatment of cancer with the use of one or more genotoxic drugs. The treatment is traditionally part of standardized regime. By utilizing the destructive properties of genotoxins treatments aims to induce DNA damage into cancer cells. Any damage done to a cancer is passed on to descendent cancer cells as proliferation continues. If this damage is severe enough, it will induce cells to undergo apoptosis. A drawback of treatment is that many genotoxic drugs are effective on cancerous cells and normal cells alike. Selectivity of a particular drug's action is based on the sensitivity of the cells themselves. So, while rapidly dividing cancer cells are particularly sensitive to many drug treatments, often normal functioning cells are affected. Another risk of treatment is that, in addition to being genotoxic, many of the drugs are also mutagenic and cytotoxic. So the effects of these drugs are not limited to just DNA damage. In addition, some of these drugs that are meant to treat cancers are also carcinogens themselves, raising the risk of secondary cancers, such as leukemia. 
This figure depicts different genotoxic based cancer treatments along with examples.
Figure-7: Genotoxic based cancer treatments
Regulatory Genetic Toxicology
• International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)
• Regulatory and pharmaceutical representatives from US, Europe & Japan
• Labor intensive process for completion of genetic toxicology guidances (1992 -1997)
• Office of Economic and Cooperation Development (OECD)
• ICH M3 –Guidance for Industry: Non-clinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals
* Prior to first human exposure
In vitro tests for the evaluation of mutations and chromosomal damage are generally needed. If an equivocal or positive finding occurs, additional testing should be performed.
* Prior to the initiation of Phase II studies
The standard battery of tests for genotoxicityshould be completed
* S2A Guideline for Industry: Specific Aspects of Regulatory GenotoxicityTests for Pharmaceuticals.
Federal Register 61:18199, 1996
* S2B Guidance for Industry: A Standard Battery for GenotoxicityTesting of Pharmaceuticals.
Federal Register 62:62472, 1997.
Purpose of Genotoxicity Test Assays
• Assays allow detection of a drug’s potential for genotoxicityearly in drug development
• Assays are inexpensive, have high statistical power, are generally reproducible and detect a variety of genotoxicend-points
• Assays designed to be more sensitive to damage in order to enhance hazard identification
Standard Genotoxicity Test Battery
• An in vitrotest for gene mutation in bacteria.
• An in vitrotest with cytogeneticevaluation of chromosomal damage with mammalian cells or an in vitro mouse lymphoma thymidinekinase(tk) assay. 
• An in vivotest for chromosomal damage using rodent hematopoieticcells
Figure-8: It displays the standard genotoxiciy test
Figure-9: It displays the thymidine kinase assay
Figure-10: Mouse lymphoma colonies soft agar plates
Figure-11: In-vitro cytogenics assay
Figure-12: CHO-CBL cell karyotypes
Figure-13: It displays the in-vivo cytogenic assay
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