Biological effects of naturally occurring and man-made fibres: in vitro cytotoxicity and mutagenesis in mammalian cells

Cytotoxicity and mutagenicity of tremolite, erionite and the man-made ceram ic (RCF-1) fibre were studied using the human-hamster hybrid A(L) cells. Re sults from these fibres were compared with those of UICC Rhodesian chrysoti le fibres. The A(L) cell mutation assay, based on the S1 gene marker locate d on human chromosome 11, the only human chromosome contained in the hybrid cell, has been shown to be more sensitive than conventional assays in dete cting deletion mutations. Tremolite, erionite and RCF-1 fibres were signifi cantly less cytotoxic to A(L) cells than chrysotile. Mutagenesis studies at the HPRT locus revealed no significant mutant yield with any of these fibr es. In contrast, both erionite and tremolite induced dose-dependent S1(-) m utations in fibre-exposed cells, with the former inducing a significantly h igher mutant yield than the latter fibre type. On the other hand, RCF-1 fib res were largely non-mutagenic. At equitoxic doses (cell survival at simila r to 0.7), erionite was found to be the most potent mutagen among the three fibres tested and at a level comparable to that of chrysotile fibres. Thes e results indicate that RCF-1 fibres are non-genotoxic under the conditions used in the studies and suggest that the high mesothelioma incidence previ ously observed in hamster may either be a result of selective sensitivity o f hamster pleura to fibre-induced chronic irritation or as a result of prol onged fibre treatment. Furthermore, the relatively high mutagenic potential for erionite is consistent with its documented carcinogenicity.