DNA修复作为烷基化致癌物器官亲和性的调节因子。

DNA repair as regulatory factor in the organotropy of alkylating carcinogens.

作者信息

Kleihues P, Doerjer G, Swenberg J A, Hauenstein E, Bücheler J, Cooper H K

出版信息

Arch Toxicol Suppl. 1979(2):253-61. doi: 10.1007/978-3-642-67265-1_21.

Abstract

Monofunctional alkylating agents which react predominantly at nitrogen atoms in DNA bases (e.g. alkyl methanesulphonates, dialkylsulfates) are generally weak carcinogens whereas compounds which lead extensively to oxygen alkylation (e.g. alkylnitrosoureas, dialkylnitrosamines, dialkyl-aryltriazenes) often exhibit a strong carcinogenic activity. O6-Alkylation of guanine is a promutagenic DNA modification possibly involved in the initiation of malignant transformation. O6-Alkylguanine can be enzymically excised and in the rat the induction of neural, renal and colonic tumors by alkylnitrosoureas, 3,3-dimethyll-phenyltriazene, dimethylnitrosamine and 1,2-dimethylhydrazine correlates with an excision repair deficiency in the target tissue. However, species and strain differences in the response to these carcinogens are not paralleled by differences in the excision repair capacity for O6-alkylguanine. Preliminary data suggest that in rat liver there is an inducible enzyme for the removal of O6-alkylguanine from DNA.

摘要

主要与DNA碱基中的氮原子发生反应的单功能烷基化剂（如烷基甲磺酸盐、硫酸二烷基酯）通常是弱致癌物，而能广泛导致氧烷基化的化合物（如烷基亚硝基脲、二烷基亚硝胺、二烷基芳基三氮烯）往往具有很强的致癌活性。鸟嘌呤的O6-烷基化是一种可能参与恶性转化起始的致突变性DNA修饰。O6-烷基鸟嘌呤可被酶切除，在大鼠中，烷基亚硝基脲、3,3-二甲基-1-苯基三氮烯、二甲基亚硝胺和1,2-二甲基肼诱发神经、肾脏和结肠肿瘤与靶组织中的切除修复缺陷相关。然而，对这些致癌物反应的物种和品系差异与O6-烷基鸟嘌呤切除修复能力的差异并不平行。初步数据表明，大鼠肝脏中存在一种可诱导的酶，用于从DNA中去除O6-烷基鸟嘌呤。