DEMETHYLATION OF METHYL MERCURY IN DIFFERENT BRAIN SITES OF MACACA-FASCICULARIS MONKEYS DURING LONG-TERM SUBCLINICAL METHYL MERCURY EXPOSURE

Total (T-Hg) and inorganic (I-Hg) mercury concentrations were determin ed in specific brain sites (cerebellum, occipital pole, pens, motor st rip, frontal pole, temporal pole, thalamus, and pituitary) of female M acaca fascicularis monkeys exposed to daily peroral doses (50 mu g Hg/ kg body weight) of methyl mercury (MeHg) for 6, 12, or 18 months, or t o continuous iv infusion of HgCl2 (200 mu g Hg/kg body wt). In normal weight monkeys (2.4-4.1 kg body wt), the average concentration of MeHg (calculated as T-Hg minus I-Hg) was about the same in all brain sites , except the pituitary-3.0 mu g Hg/g at 6 months, 4.2 mu g/g at 12 mon ths, and 4.3 mu g Hg/g at 18 months. MeHg concentrations in the pituit ary were about 50% of those in the other brain sites. In a group of mo nkeys that were kept unexposed for 6 months following 12 months of MeH g exposure, T1/2 for MeHg was about 37 days in all brain sites, with t he exception of the pituitary, where it was shorter. The concentration of I-Hg increased in all brain sites, but especially in the thalamus and pituitary, with the time of MeHg exposure. In most brain sites, I- Hg constituted about 9% of T-Hg at 6 and 12 months, and 12% of T-Hg at 18 months. In the pituitary, I-Hg increased from 20% of T-Hg at 6 mon ths to 46% at 18 months. Elimination T1/2 for I-Hg was extremely long, 230-540 days in most brain sites and considerably longer in the thala mus and pituitary. The concentration of I-Hg in the thalamus did not d ecrease during the clearance period (6 months), while I-Hg in the pitu itary continued to increase in spite of no additional exposure. The Me Hg exposed monkeys had several times higher I-Hg concentrations in the brain than monkeys exposed to HgCl2, indicating that I-Hg was formed by demethylation of MeHg in the brain, and not by brain uptake of I-Hg formed by demethylation elsewhere in the body. There were large varia tions in the relative concentration of I-Hg between individual monkeys , but not between brain sites (except thalamus and pituitary). Obese m onkeys (5.0-6.1 kg body wt) exposed to MeHg had higher concentrations of both MeHg and I-Hg than normal weight monkeys in all brain sites, e xcept in the pituitary. (C) 1995 Academic Press, Inc.