LONG CROCIDOLITE ASBESTOS FIBERS CAUSE POLYPLOIDY BY STERICALLY BLOCKING CYTOKINESIS

Asbestos has been described as a physical carcinogen in that its carci nogenic effects appear to be related primarily to fiber dimensions, It has been hypothesized that long asbestos fibers may interfere with ch romosome distribution during cell division, causing genomic changes th at lead to cell transformation and neoplastic progression, Using high- resolution time-lapse light microscopy and serial-section electron mic roscopy, we have followed individual crocidolite asbestos fibers throu gh the later stages of cell division in LLC-MK(2) epithelial cells, an d have detailed for the first time their effect on cytokinesis. We fou nd that long fibers (15-55 mu m), trapped by the cleavage furrow, ster ically blocked cytokinesis, sometimes resulting in the formation of a binucleated cell. The ends of blocking fibers were usually found withi n imaginations of the newly formed nuclei, Nuclear envelope-fiber atta chment was evident when a chromatin strand ran with the fiber into the intercellular bridge. Such strands may break, causing chromosome stru ctural rearrangements. Our data are the first to show that individual crocidolite fibers can cause genomic changes by sterically blocking cy tokinesis and that fiber length and affinity for the nuclear envelope are important factors, Such genomic changes may be among the initial e vents leading to asbestos-induced cancers.