Induction of DNA damage by dimethylarsine, a metabolite of inorganic arsenics, is for the major part likely due to its peroxyl radical.
To reveal the mechanisms of previously reported lung-specific DNA strand scissions in murine after oral administration of dimethylarsinic acid (DMAA), a main metabolite of inorganic arsenics in mammals, the ultimate substance causing DNA lesion was investigated using dimethylarsine which was a further metabolite of DMAA. The alkaline elution assay using 3H-labeled DNA showed that a major portion of the strand breaks was not suppressed by SOD and catalase, suggesting an ultimate substance other than active oxygen participated in the DNA damage. By ESR analysis, a radical estimated to be (CH3)2AsOO. was detected as a reaction product of dimethylarsine and molecular oxygen. This peroxyl radical, rather than active oxygen, was assumed to play a major role in DNA damage.
Yamanaka
K
K
Department of Hygienic Chemistry, Nihon University College of Pharmacy, Chiba, Japan.
Hoshino
M
M
Okamoto
M
M
Sawamura
R
R
Hasegawa
A
A
Okada
S
S
D020261:Arsenic Poisoning; D001152:Arsenicals; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006801:Humans; D066298:In Vitro Techniques; D007739:L Cells; D010100:Oxygen; D013481:Superoxides
D001152:Arsenicals; D005609:Free Radicals; D013481:Superoxides; C062856:dimethylarsine; D004247:DNA; D010100:Oxygen