Individual expression of carcinogen-metabolizing enzymes: cytochrome P4502A.
Expression of enzymes metabolizing drugs, carcinogens, and other chemicals ("xenobiotics") is regulated by the interplay of genetic, host, and environmental factors, leading in human populations to a marked interindividual variability. On this basis it is speculated that individual differences in cancer susceptibility could be explained to a certain extent by interindividual differences in metabolic activation. CYP dependence of carcinogen activation is briefly reviewed; CYP2A6 as a more specific example and some consequences and corollaries are briefly discussed. At present, no consensus has been reached about the significance of interindividual differences (genetic or nongenetic) in carcinogen metabolism in cancer etiology. The likely reason is that chemically induced cancer is still a multifactorial, multistage disease involving numerous events before a clinically manifested disease develops. Molecular biological methods such as RFLP and PCR-based techniques as well as molecular dosimetry are making it possible to investigate the genetic background of individual subjects and environmental influences without biases caused by diseases, age, treatment, and other factors, which have plagued studies thus far.
Pelkonen
O
O
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Raunio
H
H
D000818:Animals; D002273:Carcinogens / Q000378:metabolism / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics; D012307:Risk Factors; D013250:Steroid Hydroxylases / Q000378:metabolism*; D015262:Xenobiotics / Q000378:metabolism / Q000494:pharmacology*
D002273:Carcinogens; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; C022657:steroid hormone 6-beta-hydroxylase