人体各器官对DNA O-烷基化损伤的修复

Repair of DNA O-alkylation damage by various human organs.

作者信息

Wani A A, Wani G, D'Ambrosio S M

出版信息

Biochem Biophys Res Commun. 1985 Dec 17;133(2):589-97. doi: 10.1016/0006-291x(85)90946-5.

Abstract

Protein extracts from human adult liver, fetal liver, intestine, brain, kidney, lung and skin were tested against poly(dT)methylated X poly(dA), poly(dA)methylated X poly(dT) and methylated DNA. The suitability of various substrates was established in assays using E. coli extracts that removed O4-methylthymidine (O4-MedT), O2-MedT, and O6-methylguanine (O6-MeG). The human extracts efficiently removed O6-MeG and N3-methyladenine from methylated substrates. The adult liver exhibited low and fetal tissues negligible removal of O4-MedT. Only the liver showed limited removal of O2-MedT. The poor removal of the miscoding base O4-MedT by human organs could be an important factor in carcinogen induced mutagenesis, carcinogenesis and teratogenesis.

摘要

对来自人类成人肝脏、胎儿肝脏、肠道、大脑、肾脏、肺和皮肤的蛋白质提取物，针对聚（dT）甲基化×聚（dA）、聚（dA）甲基化×聚（dT）和甲基化DNA进行了检测。在使用能去除O4-甲基胸苷（O4-MedT）、O2-MedT和O6-甲基鸟嘌呤（O6-MeG）的大肠杆菌提取物的检测中，确定了各种底物的适用性。人类提取物能有效地从甲基化底物中去除O6-MeG和N3-甲基腺嘌呤。成人肝脏对O4-MedT的去除率较低，胎儿组织对其去除率可忽略不计。只有肝脏对O2-MedT有有限的去除。人体器官对错误编码碱基O4-MedT的去除能力较差，可能是致癌物诱导诱变、致癌和致畸的一个重要因素。