O6-alkylguanine-DNA alkyltransferase:: influence on susceptibility to the genetic effects of alkylating agents

被引：247

作者：

Kyrtopoulos, SA ^{[1
]}

机构：

[1] Natl Hellen Res Fdn, Inst Biol Res & Biotechnol, Athens 11635, Greece

来源：

TOXICOLOGY LETTERS | 1998年 / 103卷

关键词：

O-6-methylguanine; methylating agents; cytostatic drugs; N-nitroso compounds;

D O I：

10.1016/S0378-4274(98)00282-3

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

O-6-Alkylguanine-DNA alkyltransferase (AGT) repairs DNA containing O-6-alkylguanine by a suicide mechanism involving transfer of the alkyl group to its active site. In this way AGT protects cells from the mutagenic and cytotoxic effects of O-6-alkylguanine-type lesions such as O-6-methylguanine (O-6-meG), an observation which has during recent years been confirmed by studies in transgenic animals either over-expressing or completely lacking this activity. While the levels of expression of AGT have been shown to affect strongly the repair of O-6-meG after high doses of methylating agents inducing complete and prolonged depletion of the cellular AGT pool, other data suggest that within smaller variations of AGT levels (such as the interindividual variations observed in man or as observed after low or moderate exposures to alkylating agents) the dependence of O-6-meG repair is limited. This phenomenon may reflect the intracellular distribution of the repair protein and must be taken into account when assessing the role of AGT in determining susceptibility to alkylating agents of environmental or clinical significance. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.

引用

页码：53 / 57

页数：5

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