Topinka J, Loli P, Georgiadis P, Dusinská M, Hurbánková M, Kováciková Z, Volkovová K, Kazimírová A, Barancoková M, Tatrai E, Oesterle D, Wolff T, Kyrtopoulos S A
GSF-National Research Center for Environment and Health, Institute of Toxicology, Neuherberg, Germany.
Mutat Res. 2004 Sep 3;553(1-2):67-78. doi: 10.1016/j.mrfmmm.2004.06.023.
In order to get more insight into the mechanism of asbestos-related lung cancer, the mutagenic potential of asbestos was examined in vivo in rat lung. Groups of five transgenic lambda-lacI (Big Blue) rats were intratracheally instilled with single doses of 1 or 2mg, or with four weekly doses of 2mg, per animal of the amosite asbestos. Sixteen weeks after instillation, the mutation frequency was found to be increased in lung DNA by 2-fold at doses of 2 mg (P = 0.035) and of 4 x 2 mg (P = 0.007) amosite. No significant changes were observed after 4 weeks of exposure. In separate experiments, wild-type F344 rats were treated by the same regimen as described above and markers of inflammation, genotoxicity, cell proliferation and lung tissue damage were analysed. Our results indicate a weak but persistent inflammation and cell proliferation which possibly plays a major role in the observed mutagenic effect.
为了更深入了解石棉相关肺癌的发病机制，在大鼠肺内对石棉的致突变潜力进行了体内研究。将每组五只转基因λ-lacI（大蓝）大鼠经气管内单次注入每只动物1毫克或2毫克的铁石棉，或每周注入四次每次2毫克的铁石棉。注入16周后，发现肺DNA的突变频率在剂量为2毫克（P = 0.035）和4×2毫克（P = 0.007）的铁石棉时增加了2倍。暴露4周后未观察到显著变化。在单独的实验中，野生型F344大鼠接受上述相同方案的处理，并分析炎症、遗传毒性、细胞增殖和肺组织损伤的标志物。我们的结果表明存在轻微但持续的炎症和细胞增殖，这可能在观察到的致突变效应中起主要作用。
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