THE EFFECTS OF CHRONIC ETHANOL-CONSUMPTION ON CARCINOGEN METABOLISM AND ON O6-METHYLGUANINE TRANSFERASE-MEDIATED REPAIR OF ALKYLATED DNA
THE EFFECTS OF CHRONIC ETHANOL-CONSUMPTION ON CARCINOGEN METABOLISM AND ON O6-METHYLGUANINE TRANSFERASE-MEDIATED REPAIR OF ALKYLATED DNA
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DOI：
10.1111/j.1530-0277.1986.tb05184.x
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发表时间：
1986-01-01
影响因子：
3.2
通讯作者：
SALVAGNINI, M
中科院分区：
文献类型：
--
作者：
GARRO, AJ;ESPINA, N;SALVAGNINI, M
本文介绍了最近的实验进行了审查和更新与博士C。S. Lieber对与酗酒相关的癌症风险增加的潜在机制进行了研究。已发现乙醇是参与多种大鼠组织（包括肝脏、食管、肺和肠）中致癌物代谢的微粒体酶的强效诱导剂。在这些组织中，乙醇对微粒体细胞色素P-450酶活性的诱导作用可能导致不易解毒的前致癌物的亲电代谢物水平升高。此外，已发现长期乙醇喂养会抑制O 6-甲基鸟嘌呤转移酶的活性，这是一种参与修复致癌物诱导的DNA烷基化的酶。乙醇对致癌物质代谢和DNA修复的影响预计会增强化学诱导癌症的起始阶段。
This article presents a review and update of recent experiments conducted in collaboration with Dr. C. S. Lieber on mechanisms underlying the increased cancer risk associated with alcohol abuse. Ethanol has been found to be a potent inducer of microsomal enzymes involved in carcinogen metabolism in a variety of rat tissues including liver, esophagus, lungs, and intestines. In some of these tissues, ethanol's inductive effect on microsomal cytochrome P‐450 enzyme activity may result in enhanced levels of electrophilic metabolites of procarcinogens which are not readily detoxified. In addition, chronic ethanol feeding has been found to depress the activity of O6‐methylguanine transferase, an enzyme involved in the repair of carcinogen‐induced DNA alkylation. The effects of ethanol on carcinogen metabolism and on DNA repair would be expected to enhance the initiation phase of chemically induced cancers.