UBC Theses and Dissertations
Studies in selenium toxicology with particular reference to chemotherapeutic means of treatment Derrick, Jack Bryan Devereux
1. The experimental evidence of the present work in selenium toxicology is such as to cast grave doubts on the authenticity of some aspects of the work of previous investigators in this field. The response of the laboratory animals, subjected to the various procedures practised by these investigators in attempts to produce a condition of chronic selenium poisoning, suggests that these animals are, in addition to being the victims of selenium poisoning, the victims of inanition and/or dehydration. 2. The presence of up to 15 p.p.m. sodium selenite (6.9 p.p.m. Se) in the drinking water is tolerated without any drastic reduction in food and water intake by laboratory rats, provided that this concentration is reached gradually. At this level of selenium intake the animals will remain for at least 25 weeks in good condition and will exhibit growth only slightly less rapid than that of control animals. Any attempts to raise the selenium content above this level results In a compensatory lowering of the water intake and a resultant reduction in food intake of the animals. 3. The results obtained in the attempts to induce chronic selenium poisoning by dietary methods were such as to cause these methods to be abandoned due to their unsuitability for the present project. A method involving the subcutaneous injection of sub-lethal doses of sodium selenite incorporated into an absorption delaying vehicle was evolved and, after testing, was deemed suitable for the purpose of inducing a sub-acute condition of selenium toxicity to be used as a means of assessing the value of chemotherapy. 4. Experimental data on the urinary excretion levels of selenium was made available by the development of a new colorimetric procedure for the quantitative determination of selenium in biological samples. The data obtained by this method revealed that the maximum quantity of selenium excreted in the urine of rats over a period as long as ten days after injection was about one third of the quantity originally injected. No particular advantage in the use of the absorption delaying vehicle was discernable by this method but since, under the limitations imposed by the quantities of urine available, the delay in hours would be undetectable the vehicle was retained in the experiments assessing the value of BAL (2, 3-dithiopropanol) as a chemotherapeutic agent. 5. The use of BAL as a chemotherapeutic agent for combatting selenium toxicity has a deleterious effect on the intoxicated animals. The subcutaneous injection of quantities of BAL in peanut oil at levels considered well within the limits of safety resulted in an intensification of the distress of selenium injected rats. Deaths were more frequent than in the case of non BAL-treated animals. The animals which survived the effects of both poison and treatment showed a slightly higher and a more prolonged excretion of selenium in the urine. 6. Suggestions have been made for improved means of therapy for acute and sub-acute selenium poisoning involving the use of a less toxic dithiol compound and the addition of succinate to carry the animal over the initial shock to the affected enzyme systems.
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