DNA strand breaks in mammalian tissues induced by methylarsenics.
DNA damage induced by administration of dimethylarsinic acid (DMAA) to rats and mice was investigated. At 12 h after administration of DMAA, DNA single-strand breaks were induced markedly in lung. The majority of dimethylarsine, one of the main metabolites, in the expired air was excreted within 6-18 h after administration of DMAA to rats. In vitro experiments using nuclei isolated from lung of mice indicated that DNA strand breaks were caused by dimethylarsine. Furthermore, the strand breaks after exposure to dimethylarsine were reduced in the presence of catalase and/or superoxide dismutase. These results strongly suggest that the strand breaks are induced not by dimethylarsine itself but by active oxygen, e.g., O2- and .OH, produced both by dimethylarsine and molecular oxygen. When DNA was exposed to dimethylarsine, thiobarbituric acid (TBA)-reactive intermediates and cis-thymine glycol were produced. Dimethylarsine appears to induce DNA damage by the mechanism similar to the damage produced by ionizing radiation.
Yamanaka
K
K
College of Pharmacy, Nihon University, Tokyo, Japan.
Hasegawa
A
A
Sawamura
R
R
Okada
S
S
D000818:Animals; D002101:Cacodylic Acid / Q000378:metabolism / Q000633:toxicity*; D002467:Cell Nucleus / Q000187:drug effects; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D003855:Deoxyribose / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D011919:Rats, Inbred Strains; D013941:Thymine / Q000378:metabolism
D003855:Deoxyribose; D004247:DNA; D002101:Cacodylic Acid; D013941:Thymine