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结肠细胞色素P-450在大肠癌发生中的作用。

Role of colonic cytochrome P-450 in large bowel carcinogenesis.

作者信息

Strobel H W, Fang W F, Oshinsky R J

出版信息

Cancer. 1980 Mar 15;45(5 Suppl):1060-5. doi: 10.1002/1097-0142(19800315)45:5+<1060::aid-cncr2820451305>3.0.co;2-e.

DOI:10.1002/1097-0142(19800315)45:5+<1060::aid-cncr2820451305>3.0.co;2-e
PMID:6766798
Abstract

Rat colon mucosa microsomes contain a competent mixed function oxidase system that hydroxylates the N-methyl drugs benzphetamine and ethylmorphine, the O-alkyl drugs p-nitroanisole and p-nitrophenetole and the polycyclic carcinogen benzo[alpha]pyrene. The colon system's hydroxylation activities can be selectively induced by pretreatment with phenobarbital or beta-naphthoflavone and can be selectively inhibited by SKF-525A or 7,8-benzoflavone. The colon microsomal system has been solubilized with the non-ionic detergent Renex 690 and resolved by column chromatography into its components cytochrome P-450 and cytochrome P-450 reductase. Colon cytochrome P-450 and cytochrome P-450 reductase can be recombined to reconstitute hydroxylation activity. The colon system is also able to activate carcinogens to mutagenic metabolites as demonstrated in the Ames test system. In addition, the activity of the colon system is markedly increased by pretreatment with gastrointestinal hormones.

摘要

大鼠结肠黏膜微粒体含有一种活性混合功能氧化酶系统,该系统可使N-甲基药物苄非他明和乙基吗啡、O-烷基药物对硝基苯甲醚和对硝基苯乙醚以及多环致癌物苯并[a]芘发生羟基化反应。结肠系统的羟基化活性可通过苯巴比妥或β-萘黄酮预处理而被选择性诱导,也可被SKF-525A或7,8-苯并黄酮选择性抑制。结肠微粒体系统已用非离子去污剂Renex 690进行溶解,并通过柱色谱法分离成其组分细胞色素P-450和细胞色素P-450还原酶。结肠细胞色素P-450和细胞色素P-450还原酶可重新组合以重建羟基化活性。如在艾姆斯试验系统中所证实的,结肠系统也能够将致癌物激活为诱变代谢物。此外,通过胃肠道激素预处理可使结肠系统的活性显著增加。

相似文献

1
Role of colonic cytochrome P-450 in large bowel carcinogenesis.结肠细胞色素P-450在大肠癌发生中的作用。
Cancer. 1980 Mar 15;45(5 Suppl):1060-5. doi: 10.1002/1097-0142(19800315)45:5+<1060::aid-cncr2820451305>3.0.co;2-e.
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Drug metabolism in the Novikoff hepatoma: evidence for a mixed function oxidase system and partial purification of cytochrome P-450 reductase.诺维科夫肝癌中的药物代谢:混合功能氧化酶系统的证据及细胞色素P-450还原酶的部分纯化
Biochim Biophys Acta. 1978 Oct 12;526(2):345-58. doi: 10.1016/0005-2744(78)90126-2.
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Drug metabolism in rat colon: resolution of enzymatic constituents and characterization of activity.大鼠结肠中的药物代谢:酶成分的解析及活性表征
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Activation of carcinogens and mutagens by rat colon mucosa.大鼠结肠黏膜对致癌物和诱变剂的激活作用。
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Effects of cyclophosphamide and polycyclic aromatic hydrocarbons on cell growth and mixed-function oxidase activity in a human colon tumor cell line.环磷酰胺和多环芳烃对人结肠肿瘤细胞系细胞生长及混合功能氧化酶活性的影响
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The drug and carcinogen metabolism system of rat colon microsomes.大鼠结肠微粒体的药物和致癌物代谢系统。
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Purification and characterization of cytochrome P-450 specific for prostaglandin and fatty acid hydroxylase activities from the microsomes of rabbit small intestinal mucosa.兔小肠黏膜微粒体中前列腺素和脂肪酸羟化酶活性特异性细胞色素P-450的纯化与特性分析
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Influence of dietary thiamin on phenobarbital induction of rat hepatic enzymes responsible for metabolizing drugs and carcinogens.膳食硫胺素对苯巴比妥诱导大鼠肝脏中负责代谢药物和致癌物的酶的影响。
Drug Nutr Interact. 1983;2(2):117-30.

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Effect of fat and microflora on hepatic, small intestinal and colonic HMG CoA reductase, cytochrome P450 and cytochrome B5.脂肪和微生物群对肝脏、小肠及结肠中HMG CoA还原酶、细胞色素P450和细胞色素B5的影响。
Lipids. 1981 Mar;16(3):183-8. doi: 10.1007/BF02535436.
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Mol Cell Biochem. 1990 Mar 27;93(2):95-105. doi: 10.1007/BF00226181.