Thesis (Ph. D.)--University of Missouri-Columbia, 1998. / Typescript. Vita. Includes bibliographical references (leaves 141-152). Also available on the Internet.

Exposure to methyl mercury (MeHg) is a global concern. Increased chronic exposure to MeHg among fish and marine mammal consuming populations will increase the risk of prenatal exposure and as a result, the risk of infant brain damage and neurotoxcity. It is therefore important to understand the role of environmental factors, such as nutrition, in determining susceptibility to MeHg toxicity. Three nutrients (selenium (Se), vitamin C and vitamin E) were selected for examination of their interactions with the mechanisms of McHg cytotoxicity in vitro. Two hybrid neural cell lines (M03.13 and NSC-34) were evaluated for their usefulness in the study of MeHg cytotoxicity. Sixteen toxic endpoints were selected for investigation of growth, viability, structure and biochemistry. Both cell lines responded to MeHg exposure in a dose dependent manner for the majority of endpoints suggesting that both MO3.13 and NSC-34 cells undergo structural and biochemical changes during exposure to McHg, but that MO3.13 cells are more sensitive to DNA, mitochondria) membrane damage and glutathione (GSH) depletion and that NSC-34 cells are more sensitive to protein damage and apoptosis. Se exposure lessened the MeHg-induced decrease in DNA and GSH concentrations in both cell lines. In NSC-34 cells, Se also increased F-actin concentrations and prevented an increase in caspase-3 activity. Se may alter the mechanism of cell death by preventing McHg disruption of DNA replication thus maintaining the production and function of peptides (GSH) and protein (polymerized actin) that aid in MeHg detoxification and neural function. In NSC-34 cells, vitamin C prevented the induction of caspase-3 activity and lessened DNA damage and GSH depletion. Vitamin E lessened GSH depletion and lessened G-actin depletion. Both vitamin C and E improved GSH status, but vitamin C also delayed McHg damage of DNA and prevented early signs of apoptosis suggesting these two vitamins interfere with MeHg metabolism by diffe

To examine the effects of fat composition and supplemental vitamin E (Vit E) and selenium (Se) on in vivo lipid peroxidation, diet-induced hypercholesterolemia, and glutathione (GSH) metabolism, male Syrian hamsters were fed for three weeks butter fat (BF-) or fish oil- (FO-)based diets supplemented with Vit E and/or Se. The effect of supplemental Vit E and Se on tissue lipid peroxidation (LPO), glutathione peroxidase (GSH-Px) activity and GSH concentrations differed between heart and liver and also was affected by dietary fat. The reduced glutathione/oxidized glutathione (GSH/GSSG) ratio was more consistently associated with tissue lipid peroxidation than was tissue Vit E content. Plasma lipids were lowered with supplemental Se and Vit E. Se supplementation, however, exerted a more potent hypolipidemic effect than Vit E. A pro-oxidative action of Se in hearts of FO-fed hamsters was noted, which was inhibited by supplemental Vit E. Hence, the combination of Vit E and Se may offer the most benefit against diet-induced oxidative stress and hyperlipidemia.

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Male weanling inbred, mice were inoculated with fibrosarcoma cells (hindquarter) originally produced by 2-methylcholanthrene. Before inoculation, mice were randomly divided into three groups of 24 and one of 12 (control). After a one week acclimation period, each group was fed a diet containing either suboptimal vitamin B-6, 0.5 mg/kg diet; adequate, 7.0 mg/kg diet; or excess, 100 mg/kg diet. Controls were fed the adequate vitamin. B-6 diet. Twenty-four hours after tumor cell inoculation, a series of sodium selenite injections (0.5 μg/.10 mL) were given to half of each treatment group and all controls. Mice were sacrificed two wk after tumor inoculation. Tumors were excised and weighed. Selenium-treated mice had significantly smaller tumors as compared to untreated mice regardless of vitamin B-6 treatment. The smallest tumors were found in the selenium-treated group maintained on adequate B-6, while the largest tumors were developed by mice on the excess B-6 diet without selenium treatments. All groups had similar blood selenium levels as measured by gas chromatography. Tumor selenium levels, analyzed by atomic absorption, were significantly higher for untreated groups than selenium-treated groups (larger tumor size). The excess and adequate vitamin B-6 selenium-treated groups had significantly lower tumor selenium levels than the adequate vitamin B-6 untreated group. Plasma pyridoxal phosphate (concentrations) determined radiometrically and tumor vitamin B-6 levels determined microbiologically, related directly to dietary treatments. Sodium selenite injections and adequate vitamin B-6 diets reduced the size of fibrosarcomas in BALB/c inbred mice. / Master of Science

Numerous dietary factors have been shown to influence the fatty acid profiles (FAP) in breast milk from lactating women. However, few studies have evaluated the effect of trace minerals on milk FAP. Consequently, the purpose of this study was to determine the effect of selenium status on the FAP in breast milk. Subjects were lactating women from three different regions in China; Xichang (n=21), an area where selenium intakes are among the lowest in the world, Beijing (n=20), where there are adequate selenium intakes, and Enshi (n=19), where selenium intakes are among the highest in the world. Plasma and milk samples were obtained from women at birth of their baby and within 10 months postpartum and analyzed for selenium content, glutathione peroxidase (Gpx) activity and FAP. Plasma and breast milk selenium levels were significantly lower in the Xichang women and significantly higher in the Enshi women when compared to Beijing women. Despite the fact that the highest level of plasma selenium was measured in the samples from Enshi, the Gpx activity was greatest in the samples from Beijing; there was no effect of time of sampling on these samples. In breast milk, on the other hand, all the samples obtained at birth had similar activity of Gpx. The samples taken later, however, followed the same trend as plasma with the samples obtained from the women in Beijing having the highest activity. FAP indicated a significant difference in the amount of unsaturated fatty acids in both the plasma and milk for the Beijing women, when compared to the women from Xichang and Enshi. In particular, there were higher levels of linoleic acid, 18:2(n-6), in the plasma and milk of the women whose selenium intake was adequate. / Graduation date: 1997