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首页> 外文期刊>Mutation Research, E. Environmental Mutagenesis and Related Subjects >CYTOGENETIC RESPONSE TO ASBESTOS FIBERS IN CULTURED HUMAN PRIMARY MESOTHELIAL CELLS FROM 10 DIFFERENT DONORS
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CYTOGENETIC RESPONSE TO ASBESTOS FIBERS IN CULTURED HUMAN PRIMARY MESOTHELIAL CELLS FROM 10 DIFFERENT DONORS

机译：10种不同供者培养的人原代中皮细胞对石棉纤维的细胞遗传反应

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摘要

The ability of amosite asbestos fibers to induce chromosomal aberrations in human primary mesothelial cells obtained from pleural effusions of 10 noncancerous patients was investigated. The glutathione S-transferase M1 (GSTM1) genotypes of the patients were determined, since the GSTM1 null genotype has been associated with increased susceptibility to lung cancer and chemically induced cytogenetic damage. Four of the patients represented the GSTM1 null genotype, and six the GSTM1 positive genotype. Successful chromosome aberration analyses were obtained from six cases, three of them with the GSTM1 null genotype. The level of aberrant cells in unexposed cultures ranged from 2.0% to 7.5%. Statistically signfiicant increases (2.3-3.0-fold compared to controls) in the number of aberrant cells were observed in two cases only: in one case treated with 1 mu g/cm(2) of amosite, and in another treated with 2 mu g/cm(2) of amosite. Cell cultures from four individuals showed minor or no increases in the numbers of aberrant cells in the doses tested (1 and 2 mu g/cm(2)). Chromosome breaks were the major type of aberration. The amosite exposed cells with significantly increased aberrations were from patients with GSTM1 positive genotypes. Two cases that showed no cytogenetic response to asbestos fibers were of the GSTM1 null genotype. Thus, our results suggest that the lack of the GSTM1 gene does not render human mesothelial cells more susceptible to chromosomal damage induced by asbestos. GSTM1 null cells appeared, however, to be more sensitive to the growth inhibitory effects of asbestos than did GSTM1 positive cells. Variation in the cytogenetic response of human primary mesothelial cells to asbestos fibers was observed to exist, but the fibers do not appear to be potent inducers of structural chromosomal aberrations in these cells. It remains to be established whether individual sensitivity to asbestos fibers, due to specific genetic traits, exists.
机译：研究了铁石棉纤维在从10例非癌性患者的胸腔积液获得的人原代间皮细胞中诱导染色体畸变的能力。确定了患者的谷胱甘肽S-转移酶M1（GSTM1）基因型，因为GSTM1无效基因型与肺癌易感性和化学诱导的细胞遗传学损害相关。其中四名患者代表GSTM1无效基因型，六名患者表现出GSTM1阳性基因型。成功的染色体畸变分析获得了六例，其中三例具有GSTM1无效基因型。未暴露培养物中异常细胞的水平为2.0％至7.5％。仅在两种情况下，观察到异常细胞数量的统计学显着增加（是对照的2.3-3.0倍）：一种情况下，用1μg/ cm（2）的铁石棉处理，另一种情况下，用2μg的铁石棉处理/ cm（2）的铁石棉。在所测试的剂量（1和2μg / cm（2））中，来自四个个体的细胞培养物显示出异常细胞的数量很少或没有增加。染色体断裂是畸变的主要类型。畸形显着增加的暴露于铁矿的细胞来自GSTM1阳性基因型患者。没有显示出对石棉纤维的细胞遗传学应答的两个病例是GSTM1无效基因型。因此，我们的结果表明缺少GSTM1基因不会使人间皮细胞更容易受到石棉诱导的染色体损伤的影响。然而，GSTM1空细胞似乎比GSTM1阳性细胞对石棉的生长抑制作用更为敏感。观察到人原代间皮细胞对石棉纤维的细胞遗传学反应存在差异，但这些纤维似乎不是这些细胞中结构性染色体畸变的有效诱导剂。由于特定的遗传特性，是否存在对石棉纤维的个体敏感性尚待确定。

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