CYTOGENETIC RESPONSE TO ASBESTOS FIBERS IN CULTURED HUMAN PRIMARY MESOTHELIAL CELLS FROM 10 DIFFERENT DONORS

The ability of amosite asbestos fibers to induce chromosomal aberratio ns in human primary mesothelial cells obtained from pleural effusions of 10 noncancerous patients was investigated. The glutathione S-transf erase 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 positi ve genotype. Successful chromosome aberration analyses were obtained f rom six cases, three of them with the GSTM1 null genotype. The level o f aberrant cells in unexposed cultures ranged from 2.0% to 7.5%. Stati stically signfiicant increases (2.3-3.0-fold compared to controls) in the number of aberrant cells were observed in two cases only: in one c ase 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 mi nor or no increases in the numbers of aberrant cells in the doses test ed (1 and 2 mu g/cm(2)). Chromosome breaks were the major type of aber ration. The amosite exposed cells with significantly increased aberrat ions were from patients with GSTM1 positive genotypes. Two cases that showed no cytogenetic response to asbestos fibers were of the GSTM1 nu ll genotype. Thus, our results suggest that the lack of the GSTM1 gene does not render human mesothelial cells more susceptible to chromosom al damage induced by asbestos. GSTM1 null cells appeared, however, to be more sensitive to the growth inhibitory effects of asbestos than di d GSTM1 positive cells. Variation in the cytogenetic response of human primary mesothelial cells to asbestos fibers was observed to exist, b ut the fibers do not appear to be potent inducers of structural chromo somal aberrations in these cells. It remains to be established whether individual sensitivity to asbestos fibers, due to specific genetic tr aits, exists.