Inorganic arsenic methylation by rat tissue slices

Rat liver, kidney and lung slices methylate trivalent inorganic arsenic (AsIII) to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA); the liver has the greatest methylating capacity. AsIII enters the liver cells by a diffusion process followed by extensive binding to intracellular components which favors its extensive accumulation inside the cells. Reduced glutathione regulates AsIII metabolism through several mechanisms: facilitation of AsIII diffusion into the cells, stimulation of the first methylation reaction and increase of DMA excretion by the cells. An excess of AsIII inhibits DMA production by liver cells but this inhibition is reversible; mercuric ions inhibit both MMA and DMA production probably by decreasing inorganic arsenic (Asi) uptake and the second methylation reaction. DMA can be produced from MMA by rat liver slices and this methylation step is stimulated by GSH. In contrast to AsIII, AsV is not extensively taken up by the hepatocyte and is thus poorly methylated.