Thesis (Ph. D.)--University of Wisconsin--Madison, 1976. / Vita. Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 172-182).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1982. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 204-217).

Thesis--Wisconsin. / Vita. Includes bibliographical references (leaves 225-238).

Thesis (M.S.)--Oregon State University, 2008. / Printout. Includes bibliographical references (leaves 52-61). Also available on the World Wide Web.

This thesis examines the effect of combined vitamin E succinate and Asc supplementation on the in vitro growth of a non-malignant monkey kidney (LLCMK) and a malignant melanoma (BL6) cell line, with nutritional concentration ranges of 5-20µg/ml and 25-50µg/ml respectively. Vitamin E and C are thought to interact synergistically to inhibit tumour cell growth by virtue of their antioxidant properties, whereby they quench free radicals and terminate lipid peroxidation. Furthermore vitamin E and C are thought to modulate the biosynthetic pathways in arachidonic acid metabolism at a number of different points. This may also offer a means of regulating tumour cell growth. It is well documented that vitamin E and C are distributed in the lipid and aqueous phases in the cell respectively. However, the cells need to obtain the vitamins from the environment in which they are found in order to exert a growth inhibitory effect. Supplementation of combined vitamin E succinate and Asc on BL6 and LLCMK cells resulted in a significant increase in LLCMK cell growth, and a significant decrease in cell growth was observed in BL6 cells. Vitamin E succinate in its esterified form cannot function as an antioxidant and requires the cleavage of the succinate to become an active antioxidant. The metabolism of vitamin E succinate to form free vitamin E in LLCMK and BL6 cells resulted in the cleavage of the succinate group from the vitamin E molecule in BL6 cells only, thus suggesting that an esterase may be present in BL6 cells. This would allow for a synergistic interaction between the two vitamins. The arachidonic acid cascade generates a family of bioactive lipids that modulate diverse physiological and pathological responses including tumour growth and promotion. The enzyme prostaglandin endoperoxide synthase (PGHS) or cyclooxygenase (Cox) is the key enzyme in the biosynthetic pathway leading to the formation of prostaglandins. Two enzyme isoforms of Cox have been identified, Cox 1 and Cox 2. Supplementation with vitamin E succinate and Asc at a combination 20:25µg/ml respectively resulted in a trend of increasing Cox activity over 12 hours suggesting that vitamin E and Asc have a stimulatory effect on Cox activity in BL6 cells. The inhibitors of Cox 2, dexamethasone, showed a decreasing trend in Cox activity at the 20:25µg/ml combination, while cycloheximide showed an initial stimulatory effect and then a gradual decrease in Cox activity. The elimination of the Cox activity by dexamethasone suggests that transcriptional regulation may be occurring in BL6 cells. We examined by Northern blot analysis whether combined supplementation of vitamin E succinate and Asc caused an elevation of Cox 2 RNA expression in BL6 cells. An inducible effect of Cox 2 was observed after 2 hours of supplementation with a combination of vitamin E succinate and Asc in BL6 cells, however the results are inconclusive and further studies are required to substantiate this finding.

In view of the fact that some fat soluble vitamins are toxic in large doses to experimental animals and man, this study was initiated to investigate the long-term effects of low, moderate and high levels of dietary vitamin E on various metabolic parameters in the rat. Six groups of female Wistar rats (50 g) were fed for as long as 16 months the basal vitamin E-free diet with supplements ranging from 0 to 25»000 IU vitamin E (DL-a-tocopheryl acetate) per kilogram diet. The levels of vitamin E chosen were 0, 25, 250, 2,500, 10,000 and 25,000 IU/kg diet; 0 representing vitamin E-free, 25 representing moderate level and 250 to 25»000 representing large doses. All nutrients in the basal diet except vitamin E were adequate. The focus of this study was on the effects of large doses of dietary vitamin E on: (l) the hematological indices such as hematocrit and hemoglobin levels, prothrombin time and erythrocyte hemolysis at 9, 12 and 16 months of treatment; (2) urinary creatine and creatinine levels at 11 months of treatment; (3) body weight and various organ weights at 8 and 16 months of treatment; (4) femoral parameters such as ash content, and calcium and phosphate concentrations of bone at 8 and 16 months of treatment; and (5) the levels of a-tocopherol, vitamin A, total lipids, and cholesterol in liver and plasma at 8 and 16 months of treatment. Rats fed 10,000 and 25.000 IU vitamin E/kg diet for 8 and 16 months had significantly reduced body weights in comparison to those receiving the moderate level of vitamin E. The depressing effect of excess dietary vitamin E on body weight was not as marked as that of vitamin E deficiency. There was little difference between the moderate and high vitamin E supplemented groups with respect to the weights of liver, uterus and kidney. However, high levels of dietary vitamin E increased the relative heart weights after 8 months and the spleen weights after 16 months. Hemoglobin and hematocrit values were not influenced by excessive amounts of vitamin E after 9 or 12 months of treatment. At 16 months however, the hematocrit values of rats fed 10,000 and 25,000 IU vitamin E/kg diet were increased significantly over those of rats fed 25 IU/kg diet. The prothrombin time was reduced in rats treated with excess dietary vitamin E for 12 and 16 months. Only vitamin E deficiency, but not excess vitamin E, was associated with increased membrane fragility of erythrocytes. In rats subjected to excess vitamin E for 16 months the ash content of bone was decreased. High levels of dietary vitamin E increased the plasma alkaline phosphatase activity after 16 months of treatment. These results indicate that there may be increased mineral turnover in bones of rats fed high levels of vitamin E for prolonged periods. Urinary levels of creatine and creatinine were not affected by high levels of dietary vitamin E. However, in the vitamin E deficient rats, the creatine excretion increased while the creatinine excretion decreased, resulting in a very high ratio of creatine/creatinine in urine. The α-tocopherol stored in liver rose significantly with increasing dietary vitamin E. A logarithmic relation was demonstrated between liver α-tocopherol concentration and dietary levels of vitamin E. The total α-tocopherol in whole liver of rats fed the different levels of vitamin E for 16 months was approximately double that in rats treated for 8 months. A curvilinear relationship between plasma tocopherol and the logarithm of dietary vitamin E was found in rats treated for 8 and 16 months. Total lipids in liver increased significantly with increasing dietary vitamin E in rats treated for 8 months, but not in rats treated for 16 months. There was little difference in liver cholesterol concentration between the moderately supplemented and highly supplemented groups. Increasing dietary vitamin E significantly lowered plasma total lipids and cholesterol in rats treated for 16 months. A quantitative examination of the data showed that the reduction in plasma total lipids was not simply a reflection of the cholesterol levels, and suggests that a high dietary level of vitamin E affected one or more of the constituents of the total lipids (phospholipids and/or triglycerides) other than cholesterol. From the findings of this long-term study, it appears that high levels of dietary vitamin E result in biochemical changes in some aspects of metabolism in rats. Some of the changes worth recognition are the depression in body weight, increase in relative spleen and heart weights, decrease in ash content of bones with concurrent increase in plasma alkaline phosphatase activity, increased hematocrit value and fatty liver in rats treated for 8 months. A logarithmic relationship was observed between dietary levels of vitamin E and the concentrations of this vitamin in liver and plasma. The results of this study suggest that excess vitamin E over prolonged periods of time have some harmful effects in rats. / Land and Food Systems, Faculty of / Graduate

Typescript, etc. / Digitized by Kansas State University Libraries

Typescript, etc. / Digitized by Kansas State University Libraries

Typescript, etc. / Digitized by Kansas State University Libraries

No description available.