Evaluation of the causal relationship between crocidolite asbestos-induced lipid peroxidation and toxicity to macrophages.
In vitro, crocidolite asbestos toxicity to macrophages is mediated by the production of reactive oxygen metabolites. We examined whether exposure of macrophages to crocidolite asbestos induced lipid peroxidation as measured by the thiobarbituric acid assay. When elicited mouse peritoneal macrophages were exposed to crocidolite, a dose- and time-dependent increase in lipid peroxidation breakdown products accompanied cell death. Superoxide dismutase plus catalase or deferoxamine prevented both lipid peroxidation and loss of viability caused by crocidolite. We tested whether crocidolite-induced lipid peroxidation was causally responsible for cell death. Macrophages were not killed by crocidolite when incubated with 10 mM 3-aminobenzamide. The level of thiobarbituric acid-reactive material was the same, however, for cells incubated with crocidolite in the presence or absence of 3-aminobenzamide. When macrophagaes were pretreated for 24 h with 25 microM vitamin E and then incubated with crocidolite, no thiobarbituric acid-reactive products were detected. Vitamin E, however, did not prevent crocidolite cytotoxicity. These results suggest that exposure of macrophages to crocidolite asbestos produces lipid peroxidation as measured by thiobarbituric acid-reactive products. This reaction, however, is not directly responsible for irreversible injury in this model system.
Goodglick
L A
LA
Department of Pathology, Brown University, Providence, Rhode Island 02912.
Pietras
L A
LA
Kane
A B
AB
D000818:Animals; D001194:Asbestos / Q000633:toxicity*; D017638:Asbestos, Crocidolite; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015227:Lipid Peroxidation / Q000187:drug effects*; D008055:Lipids / Q000032:analysis; D008264:Macrophages / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D013997:Time Factors
D008055:Lipids; D017638:Asbestos, Crocidolite; D001194:Asbestos