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Role of Reactive Oxygen Metabolites in Crocidolite Asbestos Toxicity to Mouse Macrophages¹

Department of Pathology and Laboratory Medicine, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912

Crocidolite asbestos is toxic to macrophages in vitro. We hypothesize that this toxicity is mediated by the generation of reactive oxygen metabolites. Elicited mouse peritoneal macrophages were found to release reactive oxygen metabolites upon incubation with crocidolite asbestos in vitro. Crocidolite toxicity to both primary cultures of mouse peritoneal macrophages and P388D₁ cells, a mouse macrophage-like cell line, could be prevented by a hypoxic environment or by addition of the reactive oxygen metabolite scavengers, superoxide dismutase and catalase. In addition, if crocidolite fibers were presoaked with the iron chelator deferoxamine, no macrophage death occurred. In an attempt to mimic crocidolite-induced cytotoxicity, P388D₁ cells or primary elicited macrophages were exposed to the nontoxic mineral particle titanium dioxide in the presence and absence of ferric chloride. Titanium dioxide was only lethal when ferric chloride was added. This toxicity was prevented by superoxide dismutase, catalase, or deferoxamine. These results suggest that crocidolite-induced injury to macrophages depends on the formation of reactive oxygen metabolites. Iron present in crocidolite fibers may catalyze the production of hydroxyl radical from superoxide anion and hydrogen peroxide generated during phagocytosis. These highly reactive hydroxyl radicals are postulated to mediate lethal cell injury.

¹ This research was supported by grants from the NIH (R01 ES 03189 and K04 ES 00127). An abstract of this work was presented at the annual meeting of the American Thoracic Society on May 12–15, 1985, in Anaheim, CA, and published (59).

² Supported by a training grant from the NIH (GM 07601). To whom requests for reprints should be addressed.

Received 9/ 5/85. Revised 5/13/86. Accepted 8/ 4/86.

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