Cytochrome P450 activation of arylamines and heterocyclic amines.

Arylamines and heterocyclic arylamines (HAAs) are of particular interest because of demonstrated carcinogenicity in animals and humans and the broad exposure to many of these compounds. The activation of these, and also some arylamine drugs, involves N-hydroxylation, usually by cytochrome P450 (P450). P450 1A2 plays a prominent role in these reactions. However, P450 1A1 and 1B1 and other P450s are also important in humans as well as experimental animals. Some arylamines (including drugs) are N-hydroxylated predominantly by P450s other than those in Family 1. Other oxygenases can also have roles. An important issue is extrapolation between species in predicting cancer risks, as shown by the low rates of HAA activation by rat P450 1A2 and low levels of P450 1A2 expression in some nonhuman primates.

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