Monomethylarsonic acid reductase and monomethylarsonous acid in hamster tissue

The formation of monomethylarsonous acid (MMA(III)) by tissue homogenates o f brain, bladder, spleen, liver, lung, heart, skin, kidney, or testis of ma le Golden Syrian hamsters was assessed using [C-14]monomethylarsonic acid ( MMA(V)) as the substrate for MMA(V) reductase. The mean +/- SEM of MMA(V) r eductase specific activities (nanomoles of MMAIII per milligram of protein per hour) were as follows: brain, 91.4 +/- 3.0; bladder, 61.8 +/- 3.7; sple en, 30.2 +/- 5.4; liver, 29.8 +/- 1.4; lung, 21.5 +/- 0.8; heart, 19.4 +/- 1.5; skin, 14.7 +/-. 1.6; kidney, 10.6 +/- 0.4; and testis, 9.8 +/- 0.6. Th e concentrations of MMAIII +/-, male Golden Syrian hamster livers were dete rmined 15 h after administration of a single intraperitoneal dose of 145 mu Ci of [As-73]arsenate (2 mg of As/kg of body weight). Trivalent arsenic sp ecies (arsenite, MMA(III), and dimethylarsinous acid, DMA(III)) were extrac ted from liver homogenates using carbon tetrachloride (CCl4 and 20 mM: diet hylammonium salt of diethyldithiocarbamic acid (DDDC). Pentavalent arsenica ls (arsenate, MMAV, and dimethylarsinic acid, DMA(V)) remained in the aqueo us phase. The organic and the aqueous phases then were analyzed by HPLC. Me tabolites of inorganic arsenate present in hamster liver after 15 h were ob served in the following concentrations (nanograms per gram of liver +/- SEM ): MMA(III), 38.5 +/- 2.9; DMA(III), 49.9 +/- 10.2; arsenite, 35.5 +/- 3.0; arsenate, 118.2 +/- 8.7; MMA(V), 31.4 +/- 2.8; and DMA(V), 83.5 +/- 6.7. T his first-time identification of MMA(III) and DMAIII in liver after arsenat e exposure indicates that the significance of arsenic species in mammalian tissue needs to be re-examined and re-evaluated with respect to their role in the toxicity and carcinogenicity of inorganic arsenic.