Monomethylarsonic Acid Reductase and Monomethylarsonous Acid in Hamster Tissue

• Published in: Chemical research in toxicology Vol. 13; no. 11; pp. 1181 - 1186
• Main Authors: Sampayo-Reyes, Adriana, Zakharyan, Robert A, Healy, Sheila M, Aposhian, H. Vasken
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01-11-2000
• Subjects: Animals; Arsenates - metabolism; Arsenicals - metabolism; Brain - enzymology; Cricetinae; Liver - enzymology; Liver - metabolism; Male; Mesocricetus; monomethylarsonic acid; monomethylarsonous acid; Oxidoreductases - metabolism; reductase; Tissue Distribution; Urinary Bladder - enzymology
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/tx000154s

The formation of monomethylarsonous acid (MMAIII) by tissue homogenates of brain, bladder, spleen, liver, lung, heart, skin, kidney, or testis of male Golden Syrian hamsters was assessed using [14C]monomethylarsonic acid (MMAV) as the substrate for MMAV reductase. The mean ± SEM of MMAV reductase specific activities (nanomoles of MMAIII per milligram of protein per hour) were as follows:  brain, 91.4 ± 3.0; bladder, 61.8 ± 3.7; spleen, 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. The concentrations of MMAIII in male Golden Syrian hamster livers were determined 15 h after administration of a single intraperitoneal dose of 145 μCi of [73As]arsenate (2 mg of As/kg of body weight). Trivalent arsenic species (arsenite, MMAIII, and dimethylarsinous acid, DMAIII) were extracted from liver homogenates using carbon tetrachloride (CCl4) and 20 mM diethylammonium salt of diethyldithiocarbamic acid (DDDC). Pentavalent arsenicals (arsenate, MMAV, and dimethylarsinic acid, DMAV) remained in the aqueous phase. The organic and the aqueous phases then were analyzed by HPLC. Metabolites of inorganic arsenate present in hamster liver after 15 h were observed in the following concentrations (nanograms per gram of liver ± SEM):  MMAIII, 38.5 ± 2.9; DMAIII, 49.9 ± 10.2; arsenite, 35.5 ± 3.0; arsenate, 118.2 ± 8.7; MMAV, 31.4 ± 2.8; and DMAV, 83.5 ± 6.7. This first-time identification of MMAIII and DMAIII in liver after arsenate 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.