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 mesothelial cells. Immortalized human pleural mesothelial cells (MET 5A) were exposed in vitro to one of the following: hypoxanthine (100-200 microM) plus xanthine oxidase (10-20 mU/ml) as a superoxide-generating system, H2O2 (50 microM-5 mM); or amosite (1-100 micrograms/cm2). 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 oxidants or fibers. The effect of intracellular antioxidant enzymes and exogenous antioxidants on cell damage were investigated during oxidant 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 extracellular LDH release. Amosite exposure did not cause nucleotide depletion or induction of DNA single strand breaks. Inactivation of the intracellular antioxidant enzymes glutathione reductase or catalase augmented cell damage during H2O2 exposure but not during amosite exposure.
Kinnula
V L
VL
University of Helsinki, Department of Pulmonary Medicine, Finland.
Aalto
K
K
Raivio
K O
KO
Walles
S
S
Linnainmaa
K
K
D000227:Adenine Nucleotides / Q000378:metabolism; D000640:Amitrole / Q000633:toxicity; D017639:Asbestos, Amosite / Q000633:toxicity*; D001549:Benzamides / Q000633:toxicity; D002330:Carmustine / Q000633:toxicity; D002374:Catalase / Q000037:antagonists & inhibitors / Q000633:toxicity; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects*; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D003676:Deferoxamine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000633:toxicity; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D016877:Oxidants / Q000633:toxicity*; D013997:Time Factors
D000227:Adenine Nucleotides; D001549:Benzamides; D016877:Oxidants; D017639:Asbestos, Amosite; C025160:3-aminobenzamide; D004247:DNA; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D005980:Glutathione Reductase; D005978:Glutathione; D003676:Deferoxamine; D002330:Carmustine; D000640:Amitrole