MINERAL FIBERS INDUCE APOPTOSIS IN SYRIAN-HAMSTER EMBRYO FIBROBLASTS

It is known that asbestos and other mineral fibers induce lung cancer and mesothelioma. However, the primary mechanisms of fiber-induced car cinogenesis still remain to be elucidated. Previous studies, including our own, have shown that asbestos causes specific mitotic disturbance s, micronucleus formation and typical changes in chromatin structure r esembling those of apoptosis. This effect has been considered as progr ammed cell death removing damaged or pre-cancerous cells. We investiga ted the induction of apoptosis by asbestos (amosite, crocidolite, chry sotile) and ceramic fibers. The typical ladder pattern of DNA fragment s was identified by means of gel electrophoresis, the intracellular ca lcium concentration was measured and flow cytometry analyses were carr ied out to determine the percentage of apoptotic cells. The different fibers showed different potencies for the induction of apoptosis in Sy rian hamster embryo (SHE) cells. Depending on the type of fiber applie d 3-33% of cells underwent apoptosis. Chrysotile proved to be the most potent inducer of apoptosis compared to the other fibers. In addition , an increased intracellular calcium level was observed in apoptotic S HE cells. Chrysotile induced apoptosis after a considerably longer exp osure time (66-72 h) than cisplatin (24 h). In view of these findings we hypothesize that chrysotile induces apoptosis resulting from long-t erm changes in intracellular regulation pathways.