Fung H, Kow Y W, Van Houten B, Taatjes D J, Hatahet Z, Janssen Y M, Vacek P, Faux S P, Mossman B T
Department of Pathology, University of Vermont, Burlington 05405, USA.
Cancer Res. 1998 Jan 15;58(2):189-94.
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.
仅有两种DNA修复酶，即DNA聚合酶β和O6-甲基鸟嘌呤-DNA甲基转移酶，已被证明可在哺乳动物细胞中被基因毒性剂诱导产生。我们在此表明，青石棉可在分离的间皮细胞（恶性间皮瘤的祖细胞）中诱导DNA修复酶——脱嘌呤/脱嘧啶（AP）-内切核酸酶的产生。浓度为1.25和2.5微克/平方厘米的无毒石棉，以剂量依赖方式显著提高了大鼠胸膜间皮细胞中AP-内切核酸酶的mRNA和蛋白质水平以及酶活性（P<0.05）。这些增加在初次接触纤维后的24至72小时内持续存在。用玻璃珠（一种非致癌颗粒）未观察到变化。共聚焦扫描激光显微镜显示，AP-内切核酸酶主要定位于细胞核，但也存在于线粒体中。我们的数据首次证明了一种与氧化应激相关的人类I类致癌物可在肺的正常细胞中诱导AP-内切核酸酶的产生。
