Species differences in arsenic-mediated renal copper accumulation: a comparison between rats, mice and guinea pigs

1 Administration of arsenite leads to an accumulation of copper in the rat kidney. Owing to the high retention of arsenic in the erythrocytes, however , the rat is considered to possess special toxicokinetics of arsenic and is therefore considered less comparable with other species in this respect. 2 Therefore, we compared the effect of dietary arsenite in mice and guinea pigs with that in rats. Each species was divided into four groups of animal s according to the diets fed which contained increasing concentrations of s odium arsenite (NaAsO2; 0, 10, 30 and 60 mg As/kg of diet). Animals were ki lled after 1, 2 and 3 weeks. Tissues were sampled and analyzed for arsenic and other trace metals (Cu, Fe, Zn and Mn), 3 Compared to controls with copper levels of about 10 mu g Cu/g wet cvt, in the renal cortex, dietary administration of arsenite up to 60 mg As/kg of diet for 3 weeks to rats increased cortical levels to 65 mu g Cu/g wet wt. An increase of renal copper levels similar to that in rats, was only observ ed in guinea pigs but not in mice. Renal copper accumulation in guinea pigs tvas time- and concentration-dependent as in rats. Feeding a diet with 60 mg As/kg for 3 weeks increased cortical copper levels from about 6-40 mu g Cu/g wet wt. Renal copper levels in mice as well as other trace metal level s in guinea pigs and mice were not essentially altered by dietary arsenite. 4 The study shows that the renal copper-arsenic interaction is not restrict ed to the rat. Since in rats and guinea pigs, but not in mice, arsenic accu mulated in the kidney rather similarly, a common mechanism is suggestive. A s it was previously show in rats that only inorganic arsenic is involved in this interaction, a rapid conversion of the inorganic form into methylated metabolites as in mice may diminish the extent of the renal copper accumul ation whereas the lack of, or a less efficient, methylation as in guinea pi gs or rats increases it.