Effects of antioxidants on fiber mutagenesis

Recent studies from this laboratory have shown that asbestos fibers are mutagenic in cultured mammalian cells when assayed using a system that can detect multilocus deletions. Southern analysis of the induced mutants shows that the majority contain large deletions ranging in size from a few thousand to several million basepairs. In the present study, the effects of free radical scavenging enzymes on the cytotoxic and mutagenic potential of chrysotile fibers were examined using the human-hamster hybrid (AL) cells. Exponentially growing cells were treated with graded doses of fibers for a 24 h period either in the presence or absence of catalase, superoxide dismutase (SOD) or Tempol. Fiber-exposed cells were treated with the various enzymes either concurrently with the fiber or extended through the entire expression period. While the survival of AL cells treated with graded doses of chrysotile fibers with or without a concurrent treatment with SOD and catalase was not significantly different, the mutation yield at the S1 locus was significantly reduced in cells treated with these antioxidant enzymes. Furthermore, cells treated with the enzymes for a prolonged period were not better protected than those treated only during fiber treatment. The SOD mimic nitroxide, Tempol, had no effect on either the survival or mutagenic yield of chrysotile fibers. While SOD and catalase reduced the mutagenic potency of asbestos fibers in AL cells, they did not alter the molecular spectrum of fiber-induced mutagenesis. Our results indicate that antioxidant enzymes can protect cells against the genotoxic damages induced by chrysotile fibers, and are highly suggestive of the roles of oxyradicals in the fibrogenic and carcinogenic mechanisms of asbestos fibers.