Genetic polymorphism and variability of chemical carcinogenesis.
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.
Belitsky
G A
GA
Laboratory of Carcinogen Screening Methods, Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow 115478, Russia. gbelitsky@crc.umos.ru
Yakubovskaya
M G
MG
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002273:Carcinogens / Q000737:chemistry / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity; D011110:Polymorphism, Genetic
D002273:Carcinogens; D009153:Mutagens; D003577:Cytochrome P-450 Enzyme System; D045643:DNA Repair Enzymes