Yamanaka K, Takabayashi F, Mizoi M, An Y, Hasegawa A, Okada S
Nihon University College of Pharmacy, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan.
Biochem Biophys Res Commun. 2001 Sep 14;287(1):66-70. doi: 10.1006/bbrc.2001.5551.
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.
我们已经提出，哺乳动物体内无机砷的代谢产物二甲基胂酸（DMA）经口服，而非无机砷本身，通过代谢产生诸如二甲基砷过氧自由基[（CH(3))(2)AsOO*]等自由基，促进肺和皮肤肿瘤的发生。本研究的目的是检验二甲基胂酸是否具有诱导氧化损伤的能力。8-氧代-2'-脱氧鸟苷（8-oxodG）用作DNA氧化的生物标志物。口服DMA显著增加了8-oxodG的量，特别是在砷致癌作用的靶器官（皮肤、肺、肝脏和膀胱）以及尿液中，而亚砷酸盐则没有。因此，二甲基胂酸可能通过诱导氧化损伤，特别是碱基氧化，在砷致癌过程中发挥重要作用。
