ASBESTOS AND ERIONITE FIBERS CAN INDUCE MUTATIONS IN HUMAN-LYMPHOCYTES THAT RESULT IN LOSS OF HETEROZYGOSITY

Although asbestos and erionite are proven human carcinogens, most studies have concluded that these fibres are not mutagenic to mammalian cells in vitro. We have studied the potential of these fibres and chrysotile fibres to induce mutations in human peripheral lymphocytes, using a mutation assay that measures mutation at the autosomal HLA-A locus. Exposure of lymphocytes in culture to 400 mu g/ml of crocidolite or erionite for 72 hr did not result in a statistically significant increase in the mutation frequency (ME) in the HLA-A assay, although a trend towards increased MF was observed. Exposure to 400 mu g/ml chrysotile resulted in no increase in MF; however a significant increase was observed at 50 mu g/ml. Mutations in somatic cells can be classified according to their molecular basis. Molecular analysis of mutants obtained following exposure of lymphocytes to crocidolite and erionite demonstrated a statistically significant increase in the class of mutations arising from loss-of-heterozygosity (LOH) events involving the selection locus (HLA-A) and more distal loci. Mutations following exposure to crocidolite and erionite showed a greater frequency of LOH than did spontaneous mutants (p < 0.02 and p < 0.005 respectively). Mutants following exposure to chrysotile did not display a significant difference in LOH when compared with spontaneous mutants. Thus, although an increase in overall mutation frequency following fibre exposure did not achieve statistical significance, the modest increase seen following exposure to erionite and crocidolite is translated into a highly significant change in those components of the spectrum of mutations which result in LOH. (C) 1994 Wiley-Liss, Inc.