在Myh和Ogg1 DNA糖基化酶均有缺陷的易患肿瘤小鼠的DNA中，氧化性碱基损伤8-羟基鸟嘌呤的积累。

Accumulation of the oxidative base lesion 8-hydroxyguanine in DNA of tumor-prone mice defective in both the Myh and Ogg1 DNA glycosylases.

作者信息

Russo Maria Teresa, De Luca Gabriele, Degan Paolo, Parlanti Eleonora, Dogliotti Eugenia, Barnes Deborah E, Lindahl Tomas, Yang Hanjing, Miller Jeffrey H, Bignami Margherita

机构信息

Department of Environment and Primary Prevention, Istituto Superiore di Sanita', Rome, Italy.

出版信息

Cancer Res. 2004 Jul 1;64(13):4411-4. doi: 10.1158/0008-5472.CAN-04-0355.

DOI:10.1158/0008-5472.CAN-04-0355

PMID:15231648

Abstract

The OGG1 and MYH DNA glycosylases prevent the accumulation of DNA 8-hydroxyguanine. In Myh(-/-) mice, there was no time-dependent accumulation of DNA 8-hydroxyguanine in brain, small intestine, lung, spleen, or kidney. Liver was an exception to this general pattern. Inactivation of both MYH and OGG1 caused an age-associated accumulation of DNA 8-hydroxyguanine in lung and small intestine. The effects of abrogated OGG1 and MYH on hepatic DNA 8-hydroxyguanine levels were additive. Because there is an increased incidence of lung and small intestine cancer in Myh(-/-)/Ogg1(-/-) mice, these findings support a causal role for unrepaired oxidized DNA bases in cancer development.

摘要

OGG1和MYH DNA糖基化酶可防止DNA 8-羟基鸟嘌呤的积累。在Myh(-/-)小鼠中，脑、小肠、肺、脾或肾中未出现DNA 8-羟基鸟嘌呤随时间的积累。肝脏是这一普遍模式的例外。MYH和OGG1的失活导致肺和小肠中DNA 8-羟基鸟嘌呤随年龄增长而积累。OGG1和MYH缺失对肝脏DNA 8-羟基鸟嘌呤水平的影响是累加的。由于Myh(-/-)/Ogg1(-/-)小鼠中肺癌和小肠癌的发病率增加，这些发现支持未修复的氧化DNA碱基在癌症发展中起因果作用。