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REVIEW: Genetic Polymorphism and Variability of Chemical Carcinogenesis


G. A. Belitsky* and M. G. Yakubovskaya

Laboratory of Carcinogen Screening Methods, Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoe Shosse 24, 115478 Moscow, Russia; fax: (495) 324-1205; E-mail: gbelitsky@crc.umos.ru; belitsga@gmail.com

* To whom correspondence should be addressed.

Received December 4, 2007
Risk assessment in chemical carcinogenesis involves ratios of several factors. Individual responses of an organism to carcinogenic agents depend on polymorphism of enzymes responsible for metabolic activation/detoxification of carcinogens, DNA repair, and apoptosis, as well as promotion and progression in malignantly transformed cells. The effects of a particular polymorphic variant are manifested only in the case of its high penetrance. An integral effect is formed by the ratio of procarcinogenic and anticarcinogenic effects. The complexity of risk assessment depends on the gene polymorphism mosaic involved, directly or indirectly, in tumorigenesis and upstream/downstream interactions of gene products.
KEY WORDS: chemical carcinogenesis, gene polymorphism, cytochrome P450, DNA repair, apoptosis, promotion, initiation

DOI: 10.1134/S0006297908050076