Oral exposure of dimethylarsinic acid, a main metabolite of inorganic arsenics, in mice leads to an increase in 8-Oxo-2'-deoxyguanosine level, specifically in the target organs for arsenic carcinogenesis.
We have proposed that oral administration of dimethylarsinic acid (DMA), a metabolite of inorganic arsenics in mammals, rather than inorganic arsenics themselves, promotes lung and skin tumors by way of the metabolic production of free radicals such as dimethylarsenic peroxy radical [(CH(3))(2)AsOO*]. The purpose of the present study was to examine if dimethylarsenic has the ability to induce oxidative damage. 8-oxo-2'-deoxyguanosine (8-oxodG) was used as a biomarker of DNA oxidation. The oral administration of DMA enhanced significantly the amounts of 8-oxodG specifically in the target organs (skin, lung, liver, and urinary bladder) of arsenic carcinogenesis and also in urine, whereas arsenite did not. The dimethylarsenics thus may play an important role in arsenic carcinogenesis through the induction of oxidative damage, particularly of base oxidation.
Yamanaka
K
K
Nihon University College of Pharmacy, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan. yamanaka@pha.nihon-u.ac.jp
Takabayashi
F
F
Mizoi
M
M
An
Y
Y
Hasegawa
A
A
Okada
S
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001151:Arsenic / Q000378:metabolism; D002101:Cacodylic Acid / Q000633:toxicity*; D015197:Carcinogenicity Tests; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D002851:Chromatography, High Pressure Liquid; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D014018:Tissue Distribution
D000080242:8-Hydroxy-2'-Deoxyguanosine; D002101:Cacodylic Acid; D003849:Deoxyguanosine; D001151:Arsenic