Distinct spectrum of mutations induced by crocidolite asbestos: clue for 8-hydroxydeoxyguanosine-dependent mutagenesis in vivo.
Distinct spectrum of mutations induced by crocidolite asbestos: clue for 8-hydroxydeoxyguanosine-dependent mutagenesis in vivo.
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青石棉诱导的不同突变谱：体内 8-羟基脱氧鸟苷依赖性诱变的线索。
作者：
K. Unfried;C. Schürkes;J. Abel
活性氧或氮引起的DNA损伤被认为是石棉致癌的分子机制之一。然而，这一假说的迹象主要来自使用培养细胞或无细胞系统的体外测试。本研究对青石棉纤维的致突变性及其分子机制进行了体内研究。用LacI转基因大鼠检测间皮瘤发生的相关靶组织--大网膜DNA的突变频率。2 mg和5 mg青石棉具有致突变作用，与对照组相比，最大相对增加频率为3.4。对这些突变的分子分析显示，根据突变类型的不同，石棉诱发突变和自发突变之间存在显著差异。因此，可以提出青石棉诱变的一种不同于自发突变的特定分子机制。在青石棉诱发的突变中，已知由8-羟基脱氧鸟苷(8-OHdG)诱发的G-T颠换是最显著的突变类型(29%)。在其他实验中，测定了用1 mg或2 mg青石棉处理的大鼠大网膜DNA中的8-OHdG。青石棉处理组动物的8-OHdG水平显著高于阴性对照组。这些数据为体内活性氧或氮物种参与青石棉诱变提供了强有力的证据。
DNA damage due to reactive oxygen or nitrogen species is proposed to be involved in the molecular mechanism of asbestos-induced carcinogenicity. However, indications for this hypothesis came mainly from in vitro assays using cultured cells or cell-free systems. In the present study, the mutagenicity of crocidolite fibers and the underlying molecular mechanisms were investigated in vivo. Mutation frequencies were determined in DNA of omenta, a relevant target tissue for mesothelioma carcinogenesis, using lacI transgenic rats. The mutagenic effect of 2 and 5 mg of crocidolite asbestos was demonstrated, with a maximal relative increase in mutation frequency of 3.4 compared with the control group. The molecular analysis of the mutations revealed striking differences according to mutation types between asbestos-induced mutations and spontaneous mutations. Therefore, a specific molecular mechanism induced by crocidolite that differs from that induced by the generation of spontaneous mutations can be proposed. G to T transversions, which are known to be induced by the premutagenic DNA adduct 8-hydroxydeoxyguanosine (8-OHdG), were the most prominent mutation type (29%) within crocidolite-induced mutations. In additional experiments, 8-OHdG in DNA of omenta from rats treated with 1 or 2 mg of crocidolite asbestos was determined. Levels of 8-OHdG in animals treated with crocidolite were significantly increased compared with negative controls. These data give strong evidence for the involvement of reactive oxygen or nitrogen species in crocidolite-induced mutagenesis in vivo.
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铁和一氧化氮参与石棉对 hgprt-、gpt 中国仓鼠 V79 细胞的致突变性。
影响因子：
11.2
作者：
Park,SH;Aust,AE
通讯作者：
Aust,AE
影响因子：
3.8
作者：
A. Wylie;H. Skinner;J. Marsh;H. Snyder;C. Garzione;Damian G. Hodkinson;Roberta Winters;B. Mossman
通讯作者：
A. Wylie;H. Skinner;J. Marsh;H. Snyder;C. Garzione;Damian G. Hodkinson;Roberta Winters;B. Mossman
影响因子：
11.2
作者：
Tom K. Hei;C. Piao;Zhu Y. He;D. Vannais;C. Waldren
通讯作者：
Tom K. Hei;C. Piao;Zhu Y. He;D. Vannais;C. Waldren
影响因子：
56.9
作者：
MOSSMAN, BT;BIGNON, J;GEE, JBL
通讯作者：
GEE, JBL