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 determined in specific brain sites (cerebellum, occipital pole, pens, motor strip, frontal pole, temporal pole, thalamus, and pituitary) of female Macaca 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 to 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 months, and 4.3 mu g Hg/g at 18 months. MeHg concentrations in the pituitary were about 50% of those in the other brain sites. In a group of monkeys that were kept unexposed for 6 months following 12 months of MeHg exposure, T1/2 for MeHg was about 37 days in all brain sites, with the 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 months 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 thalamus and pituitary. The concentration of I-Hg in the thalamus did not decrease during the clearance period (6 months), while I-Hg in the pituitary continued to increase in spite of no additional exposure. The MeHg 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 variations in the relative concentration of I-Hg between individual monkeys, but not between brain sites (except thalamus and pituitary). Obese monkeys (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, except in the pituitary. (C) 1995 Academic Press, Inc.