CHRYSOTILE ASBESTOS FIBERS MEDIATE HOMOLOGOUS RECOMBINATION IN RAT2-LAMBDA FIBROBLASTS - IMPLICATIONS FOR CARCINOGENESIS

Asbestos fibers are widespread environmental carcinogens whose mutagen icity is now established. Nonetheless, the molecular nature of these m utations and the mechanisms by which they accelerate carcinogenesis re main poorly understood. We have assessed the ability of asbestos fiber s to promote homologous recombination, a potent mechanism for generati ng intrachromosomal rearrangements, such as deletions, and mitotic rec ombination. For this, we have developed a new assay which determines t he extent to which a marker gene present in DNA introduced by asbestos can recombine with homologous genes residing in a transfected cell. W e have demonstrated that Calidria chrysotile fibers are mutagenic and are able to mediate transfection of molecularly marked mutant lacI gen es in a manner that results in their preferential recombination with h omologous wild-type genes in the transfected cell. Asbestos induced re combination events may play a significant role in asbestos mutagenesis and carcinogenesis, and promotion of recombination may underlie the w ell-recognized synergy of asbestos with other carcinogens.