Induction of cytochrome P450IA genes (CYP1A) by omeprazole in the human alimentary tract.
Cytochrome P450 enzymes are capable of converting procarcinogens into either active mutagens or inactive metabolites. Because the distribution of these enzymes may be important for tissue susceptibility to procarcinogens, the expression and induction of CYP1A genes in the human alimentary tract were investigated. Endoscopic biopsy specimens were obtained from buccal mucosa, esophagus, gastric body, antrum, duodenum, and colon of 6 healthy volunteers before and 1 week after taking 20 mg of omeprazole daily. Tissue specimens were analyzed for the presence of CYP1A1 and 1A2 transcripts using hybridization methods and the polymerase chain reaction. P450-dependent enzymatic activity was assessed by deethylation of ethoxyresorufin. CYP1A1 messenger RNA (mRNA) and ethoxyresorufin activity were present constitutively in the duodenum of each volunteer. Omeprazole (20 mg/day for 1 week) induced CYP1A1 mRNA and enzymatic activity in 5 of 6 volunteers. The one individual who did not initially respond had a marked increase in both mRNA and enzymatic activity after receiving 60 mg of omeprazole daily for 1 week. After treatment with omeprazole, two individuals had low levels of CYP1A1 mRNA in several other alimentary tissues as well as low levels of CYP1A2 mRNA in the duodenum. The expression and induction by a pharmaceutical agent of CYP1A genes may have implications for intestinal metabolism of ingested xenobiotics including procarcinogens.
McDonnell
W M
WM
Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor.
Scheiman
J M
JM
Traber
P G
PG
D000328:Adult; D001483:Base Sequence; D015152:Blotting, Northern; D003106:Colon / Q000201:enzymology; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004064:Digestive System / Q000201:enzymology*; D004386:Duodenum / Q000201:enzymology; D004947:Esophagus / Q000201:enzymology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009853:Omeprazole / Q000494:pharmacology*; D010078:Oxazines / Q000378:metabolism; D010088:Oxidoreductases / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D011706:Pyloric Antrum / Q000201:enzymology; D012333:RNA, Messenger / Q000096:biosynthesis; D013270:Stomach / Q000201:enzymology
D010078:Oxazines; D012333:RNA, Messenger; C007649:ethoxyresorufin; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D009853:Omeprazole