Pelin K, Hirvonen A, Taavitsainen M, Linnainmaa K
Finnish Institute of Occupational Health, Department of Industrial Hygiene and Toxicology, Helsinki.
Mutat Res. 1995 Apr;334(2):225-33. doi: 10.1016/0165-1161(95)90015-2.
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 significant 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 microgram/cm2 of amosite, and in another treated with 2 micrograms/cm2 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 micrograms/cm2). 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.
研究了铁石棉纤维对从10名非癌症患者胸腔积液中获取的人原代间皮细胞诱导染色体畸变的能力。测定了患者的谷胱甘肽S - 转移酶M1（GSTM1）基因型，因为GSTM1缺失基因型与肺癌易感性增加以及化学诱导的细胞遗传损伤有关。其中4名患者为GSTM1缺失基因型，6名患者为GSTM1阳性基因型。6例成功进行了染色体畸变分析，其中3例为GSTM1缺失基因型。未接触石棉纤维的培养物中异常细胞水平在2.0%至7.5%之间。仅在两例中观察到异常细胞数量有统计学意义的增加（与对照组相比增加了2.3至3.0倍）：一例用1微克/平方厘米的铁石棉处理，另一例用2微克/平方厘米的铁石棉处理。来自4名个体的细胞培养物在测试剂量（1和2微克/平方厘米）下异常细胞数量仅有轻微增加或未增加。染色体断裂是主要的畸变类型。异常明显增加的铁石棉暴露细胞来自GSTM1阳性基因型的患者。两例对石棉纤维无细胞遗传学反应的患者为GSTM1缺失基因型。因此，我们的结果表明，GSTM1基因的缺失并不会使人间皮细胞更容易受到石棉诱导的染色体损伤。然而，GSTM1缺失细胞似乎比GSTM1阳性细胞对石棉的生长抑制作用更敏感。观察到人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染色体结构畸变的有效诱导剂。由于特定遗传特征导致的个体对石棉纤维的敏感性是否存在仍有待确定。
