INTERACTIONS OF INGESTED FOOD, BEVERAGE, AND TOBACCO COMPONENTS INVOLVING HUMAN CYTOCHROME P4501A2, 2A6, 2E1, AND 3A4 ENZYMES

Human cytochrome P450 (P450) enzymes are involved in the oxidation of natural products found in foods, beverages, and tobacco products and t heir catalytic activities can also be modulated by components of the m aterials. The microsomal activation of aflatoxin B-1 to the exo-8,9-ep oxide is stimulated by flavone and 7,8-benzoflavone, and attenuated by the flavonoid naringenin, a major component of grapefruit. P4502E1 ha s been demonstrated to play a potentially major role in the activation of a number of very low-molecular weight cancer suspects, including e thyl carbamate (urethan), which is present in alcoholic beverages and particularly stone brandies. The enzyme (P4502E1) is also known to be inducible by ethanol. Tobacco contains a large number of potential car cinogens. In human liver microsomes a significant role for P4501A2 can be demonstrated in the activation of cigarette smoke condensate. Some of the genotoxicity may be due to arylamines. P4501A2 is also inhibit ed by components of crude cigarette smoke condensate. The tobacco-spec ific nitrosamines are activated by a number of P450 enzymes. Of those known to be present in human liver, P4501A2, 2A6, and 2E1 can activate these nitrosamines to genotoxic products.