Methylmercury (MeHg) is a neurotoxic global pollutant that accumulates at high levels in predatory fish and marine mammals. The dietary intake of these animals is the main source of MeHg exposure in humans. At high levels, MeHg is known to damage the sensory and motor systems in both adults and children. Due to the complexity and inaccessibility of the central nervous system (CNS), early dysfunction is difficult to detect. Biochemical markers in the CNS have been used to identify MeHg neurotoxicity in animal models. Analogues of these biochemical targets are also present in peripheral blood tissue and may reflect early CNS dysfunction in human populations. The proposed peripheral biomarkers include (1) lymphocyte muscarinic acetylcholine (mACh) receptor, (2) serum cholinesterase (ChE) and (3) platelet monoamine oxidase (MAO). This thesis evaluates the effects of mercury (Hg) compounds on these CNS and peripheral biochemical markers in laboratory and epidemiological studies. In vitro studies showed that inorganic Hg (HgCl2) and MeHg inhibited mACh receptor binding in human, rat, and mouse brain tissue. Additionally, studies demonstrated that a low-level gestational exposure to MeHg reduced MAO activity in the developing embryo and in adult female offspring. Combined, these studies provide a framework for the assessment of biochemical targets of Hg compounds in humans. A cross sectional study was conducted to evaluate the association between peripheral biochemical markers and MeHg exposure in fish-eating adults (n=129) from Lac St-Pierre, Quebec. Blood-Hg concentrations were used as a marker of exposure and ranged from 0.2 to 17.0 mug/L. Multiple linear regression analysis demonstrated that both blood-Hg (p=0.011) and heavy smoking (p=0.001) were associated with reduced platelet-MAO activity. However, neither lymphocyte mACh receptor nor serum ChE was related to blood-Hg. These results suggest that exposure to MeHg may result in reduced plat

Filter-feeding macrozooplankton were collected from 24 lakes in south-central Ontario to examine relationships between environmental factors and methyl mercury accumulation. Zooplankton methyl mercury levels ranged from 19 to 448 ng$ rm cdot g sp{-1}$ dry weight in the study lakes and were highest in zooplankton from acidic brownwater lakes. Water color and lake water pH were the best predictors of methyl mercury levels in zooplankton explaining 73% of the variation. Methyl mercury concentrations were positively correlated with water color and inversely correlated with lake water pH. Water color explained a greater portion of the overall variance in methyl mercury levels, indicating that the supply of mercury from the drainage basin plays a key role in determining methyl mercury concentrations in the lacustrine biota. Zooplankton methyl mercury levels were well correlated with mercury concentrations in smallmouth bass (Micropterus dolomieui) and largemouth bass (Micropterus salmoides) from 11 of the study lakes showing zooplankton to be good indicators of the relative bioavailability of mercury at the base of the food chain.

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Methylmercury (MeHg) is the most toxic form of Hg to wildlife, partly because of its ability to biomagnify through the food chain. Previous studies have shown that river otter (Lutra canadensis) is particularly susceptible to increased exposure and body burdens of MeHg due to the piscivorous nature of its diet. The objectives of this study were to attempt to establish a relationship between MeHg concentrations in otter tissues and DNA fragmentation using single cell electrophoresis (comet assay) as well as evaluate the effectiveness of the comet assay as a tool in genotoxicity assessment in field samples. Results of preliminary experiments indicate that both time and storage temperature markedly influence the rate of spontaneous DNA degradation. Increased numbers of freeze/thaw cycling also appear to have a negative effect on DNA integrity. In addition, a cell culture experiment was set up to measure the effects of differing levels of MeHg on a neuroblastoma cell line.

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Approximately 10,000 tones of Hg are deposited annually as a result of anthropogenic activities. This increased Hg burden is known to have adverse neurological and reproductive effects on Common loons. A positive correlation between mercury (Hg) and selenium (Se) has been reported to exist in marine mammals and various species of marine and aquatic piscivorous birds. It has been hypothesized that the Hg/Se interactions may involve in the multiple mechanisms of Hg detoxification. This study focused on the suggested Hg/Se complex that forms in association with specific proteins. Specifically, this project focuses on the nature of these interactions in different tissues from wild Common loons (Gavia immer) that have been collected by the Canadian Wildlife Service. The Hg and Se concentrations in the various tissues were quantified using AAS. MALDI-TOF-MS and protein sequencing characterized the nature of the Hg/Se complex binding protein. Among the tissues, the liver had the highest concentrations of Hg and Se followed by kidney; muscle and brain. A strong association between Hg and Se was found in liver, kidney and eggs whereas there was no association in muscle and brain. In contrast brain and muscle had highest percentage of organic Hg suggesting that only inorganic Hg is associated with Se. Two Hg-Se binding protein complexes were found in liver both in the 15,200-15,300 Da range while one such complex in the same weight range was found in kidneys, when sequenced it was found that these proteins were the alpha A chain of Hemoglobin. The protein complex found in eggs was unique and although it was impossible to fully sequence it, it represents an unknown protein. The role of Se in Hg toxicity in eggs warrants further study.

This study sought to characterize the risk to human health from dietary mercury (Hg) exposure in two Inuit communities, Repulse Bay and lgloolik. Hg exposure was estimated using food frequency questionnaires. Body burden was determined by measuring Hg in hair samples. Estimated average daily Hg exposures for women of child-bearing age were 21.3 mug in Repulse Bay, and 6.0 mug in lgloolik; the general population exposures were 43.1 mug in Repulse Bay and 23.2 mug in lgloolik. Average hair concentrations were 2.1 mg/kg and 2.8 mg/kg in Repulse Bay, 2.1 mg/kg and 6.2 mg/kg in lgloolik for women of child-bearing age and the general population respectively. No participants had concentrations above the "at risk" concentration of 30 mg/kg. Significant correlations were observed between hair Hg concentration and traditional food intake. These results do not necessitate direct intervention, but validate continued monitoring of Hg exposure in Nunavut.

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