Nygren Jonas, Suhonen Satu, Norppa Hannu, Linnainmaa Kaija
Laboratory of Molecular and Cellular Toxicology, Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
Environ Mol Mutagen. 2004;44(5):477-82. doi: 10.1002/em.20066.
Mesothelioma is induced almost exclusively by exposure to asbestos fibers. We have investigated whether the induction of DNA damage in human bronchial epithelial BEAS 2B cells and human mesothelial MeT 5A cells by crocidolite asbestos (2 microg/cm2) requires the presence of asbestos fibers in the cells. DNA damage was measured microscopically by the Comet assay, and the presence of fibers in the same cells was assessed using bright-field illumination. After treatment times of 6-72 hr, damage levels were, on the average, two times higher in cells with fibers than in cells without fibers. It was further found that DNA damage decreased with time in BEAS 2B cells both with and without fibers. No decrease in damage with time was seen in MeT 5A cells, suggesting that these mesothelial cells repair the initial damage poorly, lack induction of protective systems, or constantly produce high levels of damaging species. Our results indicate that crocidolite-treated human mesothelial MeT 5A and bronchial epithelial BEAS 2B cells show an elevated level of DNA damage if they contain a fiber. In comparison with epithelial BEAS 2B cells, mesothelial MeT 5A cells have more DNA damage after the crocidolite treatment and the damage is more persistent.
间皮瘤几乎完全是由接触石棉纤维诱发的。我们研究了青石棉(2微克/平方厘米)对人支气管上皮BEAS 2B细胞和人间皮MeT 5A细胞的DNA损伤诱导是否需要细胞中存在石棉纤维。通过彗星试验在显微镜下测量DNA损伤,并使用明场照明评估同一细胞中纤维的存在情况。在6 - 72小时的处理时间后,平均而言,有纤维的细胞中的损伤水平比没有纤维的细胞高两倍。进一步发现,无论有无纤维,BEAS 2B细胞中的DNA损伤都随时间减少。在MeT 5A细胞中未观察到损伤随时间减少,这表明这些间皮细胞对初始损伤的修复能力较差,缺乏保护系统的诱导,或者持续产生高水平的损伤物质。我们的结果表明,经青石棉处理的人间皮MeT 5A细胞和支气管上皮BEAS 2B细胞如果含有纤维,其DNA损伤水平会升高。与上皮BEAS 2B细胞相比,青石棉处理后的间皮MeT 5A细胞有更多的DNA损伤,且损伤更持久。