INFLUENCE OF DIETARY LEVELS OF PROTEIN AND SULFUR AMINO-ACIDS ON THE SUBACUTE TOXICITY OF METHYLMERCURY IN MICE

The influence of diet on the subacute toxicity of methylmercury (MeHg) was investigated using C57BL/6N male mice, each fed a 24.8% protein d iet (normal protein diet, NPD), a 7.5% protein diet (low protein diet, LPD) or LPD supplemented by methionine and cystine to NPD level (amin o acid supplemented diet, ASD). When MeHg was consecutively administer ed to each group of mice (20 mu mol/kg per day), median survival times were 11, 18 and 30 d in ASD-, LPD- and NPD-fed mice, respectively. To xic symptoms including ataxia and loss of body weight were in that ord er. Hg accumulation rate in brain was faster in LPD-fed mice than in N PD-fed mice, and was further enhanced in ASD-fed mice. The fact that H g in plasma low molecular weight (LMW) fraction was in the order of AS D- > LPD- > NPD-fed mice, would be one reason for the difference in th e brain Hg accumulation. Hg levels in liver, blood and plasma showed a monotonous increase, and their terminal Hg levels were similar in the three groups. Renal Hg levels increased rapidly and almost never chan ged from the 7th d in the three groups. Urinary excretion of Hg in LPD -fed mice was markedly lower than in NPD-fed mice throughout the exper imental period; that in ASD-fed mice, which was the highest at least f or the first few days, began to decline earliest. No difference was ob served in fecal Hg levels during the early part of the experiment. Our results suggest that diet is an important factor determining the susc eptibility to subacute MeHg toxicity, and that accelerated Hg accumula tion rate in the brain caused by diet would result in higher susceptib ility to subacute MeHg toxicity.