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TISSUE DISTRIBUTION OF ARSENIC SPECIES IN MICE CHRONICALLY EXPOSED TO ARSENITE OR METHYLARSONOUS ACID
Citation:
PAUL, D., V. DEVESA I PEREZ, D. J. THOMAS, AND M. STYBLO. TISSUE DISTRIBUTION OF ARSENIC SPECIES IN MICE CHRONICALLY EXPOSED TO ARSENITE OR METHYLARSONOUS ACID. Presented at 45th Annual Society of Toxicology Meeting 2006, San Diego, CA, March 05 - 09, 2006.
Description:
e metabolism of inorganic arsenic (iAs) in humans yields toxic and carcinogenic methyl-As (MAs) and dimethyl-As (DMAs) intermediates. Methylarsonous acid (MAsIII) is the most acutely toxic species among known iAs metabolites. In this study, we examined the concentrations of As species in bladder, brain, heart, kidney, liver, lung, pancreas, fat, skeletal muscle and spleen in male C57BLK/6 mice exposed for 8 weeks to arsenite (iAsIII; 1 or 10 ppm) or MAsIII (0.1 or 1 ppm) in drinking water and in control mice drinking pure tap water. The As speciation analysis was carried out in digested tissue homogenates, using hydride generation atomic absorption spectrometry. Tissues from control mice that were exposed only to As (mainly iAs) in the diet retained significant amounts of iAs and DMAs. Exposures to 1 and 10 ppm iAsIII in drinking water increased the tissue concentrations of As species in a dose-dependent manner. Mice exposed to 1 ppm iAsIII retained predominantly DMAs and iAs in all tissues except for kidney which contained a significant amount of MAs. The lowest concentrations of As species were detected in the liver. At 10 ppm iAsIII, MAs was a significant metabolite in most tissues and the prevalent metabolite in the kidney. Notably, DMAs concentration in the bladder was an order of magnitude greater than in other tissues. Compared to controls, mice exposed to 0.1 ppm or 1 ppm MAsIII had significantly higher concentrations of iAs in the kidney and heart; iAs levels in most other organs were lower. After exposure to either 0.1 or 1 ppm MAsIII, the highest concentrations of MAs and DMAs were found in the kidney and bladder, respectively. These data suggest that exposures to both iAsIII and MAsIII result in the accumulation of MAs in the kidney and DMAs in the bladder. Thus, interactions of MAs and DMAs with specific targets in these two tissues may represent common mechanisms for adverse effects associated with chronic exposures to both iAsIII and MAsIII. (This abstract does not reflect U.S. EPA policy.)