Human cytochrome p450 2s1: lack of activity in the metabolic activation of several cigarette smoke carcinogens and in the metabolism of nicotine. Drug Metab Dispos 33

Cytochrome P450 (P450) enzymes play a critical role in the meta-bolic activation of a wide variety of environmental carcinogens. Recently, a novel human P450 enzyme, CYP2S1, has been identi-fied. It is inducible by dioxin and other classical aryl hydrocarbon receptor ligands. However, little is known regarding the substrates and the functional role of CYP2S1. Since CYP2S1 is predominantly expressed in human lung and trachea, it is reasonable to speculate that CYP2S1 may play an important role in metabolizing the envi-ronmental chemicals to which human respiratory tissues are ex-posed. In the present study, we examined the activity of human CYP2S1 in the metabolism of nicotine and in the activation of three potent carcinogens in cigarette smoke, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), benzo[a]pyrene (BaP), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The full-length CYP2S1 cDNA was amplified by nested polymerase chain reactio