The role of P450 2El and P450 2D6 genotype and phenotype polymorphism in metabolism and action of drugs and carcinogens


Klin Onkol 2001; 14(6): 193-197.

Summary: Many (pro)carcinogens are metabolized by cytochromes P450 to actual active products. Genetic polymorphism of P450 2D6 markedly influences properties of trus enzyme (phenotype) and individuals with defective enzyme may be subject to severe overdose at regular doses of some of about 40 drugs it primarily metabolizes. However, it apparently does not influence the individual sensitivity to chemical carcinogenesis. In contrast, known genetic polymorphisms of P450 2EI do not influence the activity of this enzyme, which may be increased by alcohol and some drugs and decreased by disulfuam, phenolic compounds in some vegetables and fruit. High expression of P450 2E I increases genotoxic effect ofbenzene, styrene and about 80 other important chemicals and explains mechanism by which alcohol enhances their effects. Therefore, each individual person may be responsible for decreasing the risk of exposure to chemicals known to be activated by P450 2EI by limiting the intake of alcohol. P450 2EI activity may be conveniently assessed by metabolism of chlorzoxazone to estimate individual risk of exposure to its procarcinogenic substrates. The decrease of occupational exposure to these chemicals is a more effective preventive measure, though.