On the mechanism of cell internalization of chrysotile fibers: An immunocytochemical and ultrastructural study

Human breast carcinoma cells (CG5) and human laryngeal carcinoma cells (HEp-2) were exposed to 10 and 50 μg/ml of small (about 5 μm) chrysotile asbestos fibers. Morphological and ultrastructural changes were evaluated by means of immunocytochemistry and by scanning and transmission electron microscopy. Our attention was focused on the mechanisms of cell internalization and on transport of chrysotile fibers. The fibers appeared to penetrate the cell cytoplasm and to be translocated in proximity of the nucleus. Small chrysotile fibers could also be found inside the nucleus of interphase cells. Involvement of the main cytoskeletal components, i.e., microfilaments, intermediate filaments, and microtubles, in the cytotoxicity of chrysotile fibers was also evaluated. Our findings suggest that after fiber penetration, a rearrangement of the cytoskeletal apparatus occurs. It has also been observed that small fibers remain associated with the cytoskeletal framework, which can thus play a role in asbestos intracytoplasmic translocation in epithelial cells. Furthermore, after the cell has completely recovered its morphology, fiber internalization ultimately seems to lead to the formation of giant multinucleated cells. These data could be indicative of an interaction occurring between asbestos fibers and the normal mitotic process. The disturbance of the cell cytoskeleton and the close morphologic contact between asbestos fibers and the cell's nuclear region may be of importance in explaining the well-known carcinogenic effects of asbestos mineral fibers.