Contributions of Human Enzymes in Carcinogen Metabolism

Considerable support exists for the roles of metabolism
in modulating the carcinogenic properties of chemicals. In particular,
many of these compounds are pro-carcinogens that require activation
to electrophilic forms to exert genotoxic effects. We systematically
analyzed the existing literature on the metabolism of carcinogens
by human enzymes, which has been developed largely in the past 25
years. The metabolism and especially bioactivation of carcinogens
are dominated by cytochrome P450 enzymes (66% of bioactivations).
Within this group, six P450s1A1, 1A2, 1B1, 2A6, 2E1, and 3A4accounted
for 77% of the P450 activation reactions. The roles of these P450s
can be compared with those estimated for drug metabolism and should
be considered in issues involving enzyme induction, chemoprevention,
molecular epidemiology, interindividual variations, and risk assessment.