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 stud ies have concluded that these fibres are not mutagenic to mammalian ce lls in vitro. We have studied the potential of these fibres and chryso tile 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 e rionite for 72 hr did not result in a statistically significant increa se 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 obs erved at 50 mu g/ml. Mutations in somatic cells can be classified acco rding to their molecular basis. Molecular analysis of mutants obtained following exposure of lymphocytes to crocidolite and erionite demonst rated a statistically significant increase in the class of mutations a rising from loss-of-heterozygosity (LOH) events involving the selectio n locus (HLA-A) and more distal loci. Mutations following exposure to crocidolite and erionite showed a greater frequency of LOH than did sp ontaneous mutants (p < 0.02 and p < 0.005 respectively). Mutants follo wing exposure to chrysotile did not display a significant difference i n LOH when compared with spontaneous mutants. Thus, although an increa se in overall mutation frequency following fibre exposure did not achi eve statistical significance, the modest increase seen following expos ure to erionite and crocidolite is translated into a highly significan t change in those components of the spectrum of mutations which result in LOH. (C) 1994 Wiley-Liss, Inc.