INDUCTION OF CYTOCHROME P4501A BY SMOKING OR OMEPRAZOLE IN COMPARISONWITH UDP-GLUCURONOSYLTRANSFERASE IN BIOPSIES OF HUMAN DUODENAL MUCOSA

Drug-metabolizing enzymes were investigated in duodenal biopsy specime ns. Cytochrome P4501A (CYP1A) activity was determined by measuring 7-e thoxyresorufin O-deethylase (EROD) activity in biopsies from 20 smoker s (3-30 cigarettes per day), 21 nonsmokers, and 10 nonsmokers receivin g omeprazole treatment (20-60 mg/day for at least 1 week). Omeprazole is known to act as a polycyclic aromatic hydrocarbon (PAH)-type induce r in humans. EROD activity was found to be significantly induced in sm okers and omeprazole-treated patients, with medians of 2.1 and 1.1 pmo l.min(-1) min(-1) mg protein(-1), respectively, compared with 0.5 pmol min(-1) mg protein(-1) in nonsmokers. Immunoblot analysis substantiat ed that EROD activity was correlated with CYP1A protein. In contrast, UDP-glucuronosyltransferase (UGT) activity towards 4-methylumbellifero ne (an overlapping substrate of several constitutive and inducible UGT s) was not significantly affected. The results demonstrate CYP1A induc tion by omeprazole and by constituents of cigarette smoke in the human duodenum and support the utility of duodenal biopsies to monitor CYP1 A induction by PAH-type inducers.