INDUCTION OF CYTOCHROME-P450IA GENES (CYP1A) BY OMEPRAZOLE IN THE HUMAN ALIMENTARY-TRACT

被引:109
作者
MCDONNELL, WM
SCHEIMAN, JM
TRABER, PG
机构
[1] UNIV MICHIGAN,SCH MED,DEPT INTERNAL MED,DIV GASTROENTEROL,ANN ARBOR,MI 48104
[2] VET ADM MED CTR,ANN ARBOR,MI 48105
关键词
D O I
10.1016/0016-5085(92)91171-Y
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 CYPlA 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. CYP1Al 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. © 1992.
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页码:1509 / 1516
页数:8
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