CYTOTOXICITY OF OXIDANTS AND ASBESTOS FIBERS IN CULTURED HUMAN MESOTHELIAL CELLS

The authors investigated the mechanisms caused by oxidants (superoxide and hydrogen peroxide) and asbestos (amosite) fibers in human mesothe lial cells. Immortalized human pleural mesothelial cells (MET 5A) were exposed in vitro to one of the following: hypoxanthine (100-200 mu M) plus xanthine oxidase (10-20 mU/ml) as a superoxide-generating system , H2O2 (50 mu M-5 mM); or amosite (1-100 mu g/cm(2)). Cellular adenine nucleotide depletion, DNA single strand breaks, extracellular release of nucleotides, and their catabolites and lactate dehydrogenase (LDH) were assessed as markers of cell damage after 4-6 h exposure to the o xidants or fibers. The effect of intracellular antioxidant enzymes and exogenous antioxidants on cell damage were investigated during oxidan t and amosite exposure. Superoxide radical and H2O2 exposure resulted in the depletion of adenine nucleotides, accumulation of the products of nucleotide catabolism, induction of DNA single strand breaks, and e xtracellular LDH release. Amosite exposure did not cause nucleotide de pletion or induction of DNA single strand breaks. Inactivation of the intracellular antioxidant enzymes glutathione reductase or catalase au gmented cell damage during H2O2 exposure but not during amosite exposu re.