Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells.
Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells.
复制标题
DOI：
--
复制
发表时间：
1998-01
期刊：
影响因子：
11.2
通讯作者：
H. Fung;Y. Kow;B. V. Houten;D. Taatjes;Z. Hatahet;Yvonne W. M. Janssen;P. Vacek;S. Faux;B. Moss
中科院分区：
文献类型：
--
作者：
H. Fung;Y. Kow;B. V. Houten;D. Taatjes;Z. Hatahet;Yvonne W. M. Janssen;P. Vacek;S. Faux;B. Moss
只有两种DNA修复酶，DNA聚合酶β和o6 -甲基鸟嘌呤-DNA甲基转移酶，已被证明是由遗传毒性物质诱导的哺乳动物细胞。我们在这里发现，石棉石在分离的间皮瘤细胞中诱导DNA修复酶，无嘌呤/无嘧啶(AP)-核酸内切酶，恶性间皮瘤的祖细胞。无毒性浓度为1.25和2.5 μ g/cm2的石棉显著提高了大鼠胸膜间皮细胞ap -内切酶mRNA和蛋白水平以及酶活性（P < 0.05），并呈剂量依赖性。这些增加在初始暴露于纤维后24至72小时内持续存在。玻璃微珠（一种非致癌颗粒）没有观察到变化。激光共聚焦扫描显微镜显示，ap -内切酶主要定位于细胞核，但也定位于线粒体。我们的数据首次证明了与氧化应激相关的人类I类致癌物在正常肺细胞中诱导ap -内切酶的能力。
Only two DNA repair enzymes, DNA polymerase beta and O6-methylguanine-DNA methyltransferase, have been shown to be inducible in mammalian cells by genotoxic agents. We show here that crocidolite asbestos induces the DNA repair enzyme, apurinic/apyrimidinic (AP)-endonuclease, in isolated mesothelial cells, the progenitor cells of malignant mesothelioma. Asbestos at nontoxic concentrations of 1.25 and 2.5 microg/cm2 significantly increased AP-endonuclease mRNA and protein levels as well as enzyme activity (P < 0.05) in a dose-dependent manner in rat pleural mesothelial cells. These increases were persistent from 24 to 72 h after initial exposure to fibers. Changes were not observed with glass beads, a noncarcinogenic particle. Confocal scanning laser microscopy showed that AP-endonuclease was primarily localized in the nucleus but also in mitochondria. Our data are the first to demonstrate the inducibility of AP-endonuclease by a human class I carcinogen associated with oxidant stress in normal cells of the lung.