Induction of cytochrome P450IA genes (CYP1A) by omeprazole in the human alimentary tract.
Induction of cytochrome P450IA genes (CYP1A) by omeprazole in the human alimentary tract.
复制标题
奥美拉唑在人类消化道中诱导细胞色素 P450IA 基因 (CYP1A)。
DOI：
10.1016/0016-5085(92)91171-y
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发表时间：
1992
期刊：
影响因子：
29.4
通讯作者：
Traber,PG
中科院分区：
文献类型：
--
作者：
McDonnell,WM;Scheiman,JM;Traber,PG
细胞色素P450酶能够将原致癌物转化为活性诱变剂或非活性代谢物。由于这些酶的分布可能对组织对前致癌物的敏感性很重要，因此研究了CYP 1A基因在人消化道中的表达和诱导。在每日服用20 mg奥美拉唑之前和之后1周，从6名健康志愿者的颊粘膜、食管、胃体、胃窦、十二指肠和结肠获得内窥镜活检标本。使用杂交方法和聚合酶链反应分析组织标本中是否存在CYP 1A 1和1A 2转录本。通过乙氧基试卤灵的脱乙基化来评估P450依赖性酶活性。CYP 1A 1信使RNA（mRNA）和乙氧基试卤灵活性存在于每个志愿者的十二指肠组成。奥美拉唑（20 mg/天，持续1周）在6名志愿者中的5名中诱导CYP 1A 1 mRNA和酶活性。一名最初没有反应的个体在接受每日60 mg奥美拉唑1周后，mRNA和酶活性均显著增加。奥美拉唑给药后，2例受试者的其他几种消化组织中的CYP 1A 1 mRNA水平较低，十二指肠中的CYP 1A 2 mRNA水平也较低。药物对CYP 1A基因的表达和诱导可能对摄入的外源性物质（包括前致癌物）的肠道代谢有影响。
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 ofCYPlAgenes 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 ofCYP1Agenes may have implications for intestinal metabolism of ingested xenobiotics including procarcinogens.