Animal species difference in the uptake of dimethylarsinous acid (DMA(III)) by red blood cells

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 (DMA(V)) an d dimethylarsinous (DMA(III)) acids were incubated with rat, hamster, mouse , and human RBCs, and the uptake rates and chemical forms of arsenic were d etermined. Although DMA(V) was practically not or taken up slowly by RBCs o f all the present animal species, DMA(III) was taken efficiently in the ord er of rat > hamster > human, RBCs of mice taking it up less efficiently and with a different pattern from the former three animals. Further, although DMA(III) taken up by rat RBCs was retained, that by hamster ones was efflux ed in the form of DMA(V). The uptake of DMA(III) and efflux of DMAV took pl ace much more slowly in human RBCs than rat and hamster ones. The uptake of DMA(III) by RBCs was inhibited on the oxidation of glutathione with diamid e. Incubation of DMA(III), but not of DMA(V), with a hemolysate produced a high molecular weight complex, which increases in the presence of glutathio ne, suggesting that DMA(III) taken up by RBCs is retained through the forma tion of a complex with protein(s) specific to animal species, and effluxed from RBCs after being oxidized to DMA(V). These results indicate that DMA i s taken up by RBCs in the form of DMA(III), and that the uptake and efflux rates are dependent on the animal species, the effluxed arsenic being DMA(V ). The present results suggest that the uptake of DMA by RBCs is an additio nal contributing factor to the animal species difference in the metabolism of arsenic in addition to the reduction and methylation capacity in the liv er.