Chen Q, Marsh J, Ames B, Mossman B
Department of Biochemistry and Molecular Biology, University of California, Berkeley 94720, USA.
Carcinogenesis. 1996 Nov;17(11):2525-7. doi: 10.1093/carcin/17.11.2525.
Crocidolite asbestos is associated with the development of mesothelioma. Although chromosomal changes have been documented in mesothelial cells, the mechanisms of interaction of crocidolite with DNA remain obscure. Since human mesothelial cells are exquisitely sensitive to asbestos, oxidative DNA damage was measured in an asbestos-exposed human mesothelial cell line (MET5A) by assaying oxidized guanine bases [8-oxo-2'-deoxyguanosine (oxo8dG), 8-oxoguanine (oxo8G), and 8-oxoguanosine (oxo8Gua)] excreted into the spent culture medium after DNA repair or turnover. At growth inhibitory, but not cytolytic concentrations, asbestos caused significant elevation of all bases in the spent medium over a 48-h period. In contrast, riebeckite, a chemically similar, nonfibrous analog of crocidolite did not cause increased adduct release. Results show that oxidative RNA and DNA bases are produced in response to asbestos in target cells of asbestos-induced cancers.
青石棉与间皮瘤的发生有关。尽管已在间皮细胞中记录到染色体变化，但青石棉与DNA相互作用的机制仍不清楚。由于人类间皮细胞对石棉极为敏感，因此通过检测DNA修复或周转后排泄到用过的培养基中的氧化鸟嘌呤碱基[8-氧代-2'-脱氧鸟苷（oxo8dG）、8-氧代鸟嘌呤（oxo8G）和8-氧代鸟苷（oxo8Gua）]，在暴露于石棉的人类间皮细胞系（MET5A）中测量氧化DNA损伤。在生长抑制而非细胞溶解浓度下，石棉在48小时内导致用过的培养基中所有碱基显著升高。相比之下，镁钠闪石，一种化学性质相似的青石棉非纤维类似物，不会导致加合物释放增加。结果表明，在石棉诱发癌症的靶细胞中，氧化RNA和DNA碱基是对石棉产生的反应。
