Strain-dependent disposition of inorganic arsenic in the mouse

Recent studies have suggested that polymorphisms in the methylation of inor ganic arsenic (iAs) exist in animals and humans. Methylation of iAs is an i mportant step in the elimination of arsenic. The objective of this study wa s to examine whether there are differences in iAs disposition, and hence me thylation, between three strains of mice. Ninety-day-old female mice (strai ns: C3H/HeNCrlBR, C57BL/6NCrlBR, and B6C3F1/CrlBR) were administered [As-73 ]arsenate or [As-73]arsenite orally at dose levels of 0.5 or 5.0 mg As/kg. Another group of mice were administered [As-73]arsenate (5.0 mg As/kg) intr aperitoneally (i.p.). Disposition of [As-73] was assessed by whole-body cou nting, and analysis of urine, feces and tissues for radioactivity. Urine wa s analyzed by chromatography for arsenic metabolites. Several strain- and d ose-related effects in the disposition of [As-73] were observed with both a rsenicals. After oral administration, the clearance of [As-73]arsenate, mea sured by whole-body counting, was dependent on the strain. However, because there was no strain dependence on clearance of [As-73]arsenate administere d i.p., the effect after oral administration may be due to a difference in absorption of arsenate between the strains. With increased oral dose of ars enate and arsenite, the clearance of [As-73] was slower and there was highe r tissue retention of [As-73]. The percentage of metabolites excreted in ur ine also was affected by the administered dose. With increased dose, the pe rcentage of arsenite and monomethylarsonic acid were significantly increase d, and dimethylarsinic acid decreased. However, our results suggest there i s no overall difference between these strains of mice with respect to dispo sition of iAs. A better understanding of the role of phenotype in the dispo sition and toxicity of iAs would reduce the uncertainty in arsenic risk ass essment. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.