Effect of vitamin B12 status on selenium methylation and toxicity in rats: in vivo and in vitro studies

Animals are known to convert inorganic selenium to less toxic methylated compounds such as dimethylselenide (DMSe) and trimethylselenonium (TMSe). This study investigated the role of vitamin B12, a cofactor of methionine synthetase, in selenium methylation in the rat. Vitamin B12-depleted rats expired 16% of dosed 75Se-selenite as DMSe compared to 45% for control rats and excreted less TMSe in the urine (6.1% of dose) than control (9% of dose) rats. At the same time, higher (p < 0.05) tissue (liver, kidney, muscle) selenium levels and lower (p < 0.05) blood selenium levels were found in vitamin B12-deficient rats. Primary hepatocytes from vitamin B12-deficient rats volatilized 15% of selenite in incubation medium in 5 hr as compared to 49% in hepatocytes from control rats. Hepatocytes from vitamin B12-deficient rats were less resistant to selenite toxicity. In vitro methylation of selenium with liver extract from vitamin B12-deficient rats showed one-third to one-half the rate of volatilization of selenium as compared to control rats. S-adenosylmethionine was required for this reaction. These results show that vitamin B12 deficiency significantly decreases the ability of rats to methylate selenium.