Induction of metaphase and anaphase/telophase abnormalities by asbestos fibers in rat pleural mesothelial cells in vitro.

The cytogenetic effects of asbestos fibers on rat pleural mesothelial cells were studied in vitro. Crocidolite UICC significantly enhanced aneuploidy and produced few structural chromosome aberrations, whereas anatase, an isomorphic particle, induced no numerical or structural changes. Mitomycin C (300 nM) produced a tenfold increase in abnormal anaphases compared with controls. Asbestos produced anaphase/telophase abnormalities in a concentration-dependent manner. The majority of the abnormalities involved lagging chromosomes. Crocidolite UICC induced abnormalities at a dose of 7.0 micrograms/cm2, whereas Canadian chrysotile did so at 1.0 to 2.0 micrograms/cm2. When the response was assessed by the number of long and thin fibers per cm2 (length > 8 microns; diameter < or = 0.25 microns), crocidolite UICC produced more abnormalities than Canadian chrysotile at all concentrations. On a per-weight basis, these findings differ from those obtained after intrapleural inoculation, as crocidolite induced more mesotheliomas than chrysotile; however, on a per-fiber basis, the in vitro and in vivo effects were similar. These results show that anaphase/telophase analysis is sensitive and complementary to metaphase analysis, and suggest that asbestos might produce cell transformation by inducing chromosome missegregation and aneuploidy.