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Animal Species Difference in the Uptake of Dimethylarsinous Acid (DMA III ) by Red Blood Cells

2001; American Chemical Society; Volume: 14; Issue: 10 Linguagem: Inglês

10.1021/tx015537k

1520-5010

Yamato Shiobara, Yasumitsu Ogra, Kazuo Suzuki,

Heavy Metal Exposure and Toxicity

The animal species difference in the metabolism of arsenic was studied from the viewpoint of the mechanism underlying its distribution in the form of dimethylated arsenic in red blood cells (RBCs). Dimethylarsinic (DMAV) and dimethylarsinous (DMAIII) acids were incubated with rat, hamster, mouse, and human RBCs, and the uptake rates and chemical forms of arsenic were determined. Although DMAV was practically not or taken up slowly by RBCs of all the present animal species, DMAIII was taken efficiently in the order of rat > hamster > human, RBCs of mice taking it up less efficiently and with a different pattern from the former three animals. Further, although DMAIII taken up by rat RBCs was retained, that by hamster ones was effluxed in the form of DMAV. The uptake of DMAIII and efflux of DMAV took place much more slowly in human RBCs than rat and hamster ones. The uptake of DMAIII by RBCs was inhibited on the oxidation of glutathione with diamide. Incubation of DMAIII, but not of DMAV, with a hemolysate produced a high molecular weight complex, which increases in the presence of glutathione, suggesting that DMAIII taken up by RBCs is retained through the formation of a complex with protein(s) specific to animal species, and effluxed from RBCs after being oxidized to DMAV. These results indicate that DMA is taken up by RBCs in the form of DMAIII, and that the uptake and efflux rates are dependent on the animal species, the effluxed arsenic being DMAV. The present results suggest that the uptake of DMA by RBCs is an additional contributing factor to the animal species difference in the metabolism of arsenic in addition to the reduction and methylation capacity in the liver.