EFFECTS OF ANTIOXIDANTS ON FIBER MUTAGENESIS

Recent studies from this laboratory have shown that asbestos fibers ar e mutagenic in cultured mammalian cells when assayed using a system th at can detect multilocus deletions, Southern analysis of the induced m utants shows that the majority contain large deletions ranging in size from a few thousand to several million basepairs, In the present stud y, the effects of free radical scavenging enzymes on the cytotoxic and mutagenic potential of chrysotile fibers were examined using the huma n-hamster hybrid (A(L)) cells, Exponentially growing cells were treate d with graded doses of fibers for a 24 h period either in the presence or absence of catalase, superoxide dismutase (SOD) or Tempol. Fiber-e xposed cells were treated with the various enzymes either concurrently with the fiber or extended through the entire expression period, Whil e the survival of A(L) cells treated with graded doses of chrysotile f ibers with or without a concurrent treatment with SOD and catalase was not significantly different, the mutation yield at the S1 locus was s ignificantly reduced in cells treated with these antioxidant enzymes. Furthermore, cells treated with the enzymes for a prolonged period wer e 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 reduc ed the mutagenic potency of asbestos fibers in A(L) cells, they did no t alter the molecular spectrum of fiber-induced mutagenesis, Our resul ts indicate that antioxidant enzymes can protect cells against the gen otoxic damages induced by chrysotile fibers, and are highly suggestive of the roles of oxyradicals in the fibrogenic and carcinogenic mechan isms of asbestos fibers.