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. 1994 Sep;102(Suppl 3):37–40. doi: 10.1289/ehp.94102s337

Induction of lung-specific DNA damage by metabolically methylated arsenics via the production of free radicals.

K Yamanaka 1, S Okada 1
PMCID: PMC1567413  PMID: 7843134

Abstract

To clarify the genotoxicity of inorganic arsenics, we focused on the genotoxic effect of metabolically methylated arsenics in mammals. Oral administration to mice of dimethylarsinic acid (DMAA), a major metabolite of inorganic arsenics, induced lung-specific DNA damage, i.e., DNA single-strand breaks and the clumping of heterochromatin. The lung-specific strand breaks were not caused by DMAA itself, but by dimethylarsine, a further metabolite of DMAA. An in vitro experiment indicated that DNA single-strand breaks by dimethylarsine were suppressed by the presence of superoxide dismutase and catalase, suggesting that the strand breaks were induced via the production of free-radical species including active oxygens. Dimethylarsenic peroxyl radical [(CH3)2AsOO.] and superoxide anion radical produced from the reaction between molecular oxygen and dimethylarsine were detected by electron-spin resonance analysis using a spin-trapping agent and the cytochrome-c method, respectively. Of these two radicals, the dimethylarsenic peroxyl radical rather than the superoxide anion radical is assumed to play the dominant role in causing the DNA damage, at least for DNA single-strand breaks.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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