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Mercury is a potent toxicant of concern to both the general public and occupationally exposed workers (e.g., dentists). Recent studies suggest that several genes mediating the toxicokinetics of mercury are polymorphic in humans and may influence inter-individual variability in mercury accumulation. This work hypothesizes that polymorphisms in key glutathione synthesizing enzyme, glutathione S-transferase, and selenoprotein genes underlie inter-individual differences in mercury body burden as assessed by analytical mercury measurement in urine and hair, biomarkers of elemental mercury and methylmercury, respectively. Urine and hair samples were collected from a population of dental professionals (n=515), and total mercury content was measured. Average urine (1.06±1.24 microg/L) and hair mercury levels (0.49±0.63 microg/g) were similar to national U.S. population averages. Taqman assays were used to genotype DNA from buccal swab samples at 15 polymorphic sites in genes implicated in mercury metabolism. Linear regression modeling assessed the ability of polymorphisms to modify the relationship between mercury biomarker levels and exposure sources (e.g., amalgams, fish consumption). Five polymorphisms were significantly associated with urine mercury levels (GSTT1 deletion), hair mercury levels (GSTP1-105, GSTP1-114, GSS 5'), or both (SEPP1 3'UTR). Overall, this study suggests that polymorphisms in selenoproteins and glutathione-related genes may influence elimination of mercury in the urine and hair or mercury retention following exposures to elemental mercury (via dental amalgams) and methylmercury (via fish consumption)., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Studies were conducted to define the specific changes in the urinary porphyrin excretion pattern (porphyrin profile) and the time course of those changes in rats exposed to mercury as methyl mercury hydroxide (MMH) at 5 or 10 ppm in the drinking water for up to 30 weeks. The urinary porphyrin profile elicited by MMH is uniquely characterized by highly elevated levels of 4- and 5-carboxyl porphyrins, and of a third atypical porphyrin with as yet undetermined chemical characteristics. Changes in the porphyrin profile were observed as early as 1 or 2 weeks following initiation of exposure to MMH at 10 or 5 ppm, respectively, and were sustained as long as 40 weeks following cessation of MMH treatment. The magnitude of the urinary porphyrin profile at either MMH dose level increased progressively during the course of mercury treatment and was highly correlated with the renal mercury concentration. A subsequent decline in the magnitude of the urinary porphyrin profile in animals exposed to 10 ppm MMH for more than 10 weeks was associated with the accumulation of high levels of Hg2+ in kidney cells and loss of renal functional status. These findings demonstrate that mercury elicits a unique change in the urinary porphyrin excretion pattern which is related to the dose and duration of mercury treatment. The association of urinary porphyrin excretion rates with renal mercury content and functional status suggests that urinary porphyrin profiles may serve as a useful biomarker of mercury accumulation and nephrotoxicity during prolonged mercury exposure.

Rats were given a total dose of 50 mg/kg (Exp. 1), 13.3 or 40 mg/kg (Exp. 2), or 40 mg/kg (Exp. 3) of methyl mercury chloride subcutaneously over a course of 5 days. At varying times after the toxic exposure, up to 1 year, their sensory functioning was assessed by reflex modulation methods: stimuli of interest were presented just before an intense tone which elicited the startle reflex, and stimulus reception was measured by the inhibitory control of the stimuli over the amplitude of the reflex. In Experiment 1 cutaneous prestimuli (electric shock to the tail) and brief acoustic transients (silent periods in noise) were less effective inhibitors of reflex activity in poisoned animals, compared to controls, indicating that the poisoned animals had impairments in cutaneous sensitivity and audition. In Experiment 2 the time course of sensory loss and subsequent recovery was studied. Impaired auditory function was shown further by a deficit in the effectiveness of weak noise pulses, and, in addition, the cutaneous deficit for weak tail shocks was accompanied by an exaggerated or hyperpathic response to more intense tail shocks. Experiment 3 confirmed the finding that the loss of sensitivity to weak shock was accompanied by an enhancement of the response to more intense shock. These data were related to peripheral neuropathy and shown to be analogous to certain clinical symptoms of Minamata disease reported in humans.