Experiments were undertaken to study in vivo the effect of hexachloronaphthalene in vitamin A metabolism in the rat. The status of vitamin A in the animal was determined by tissue analysis for the vitamin and by visual observation for symptoms of vitamin A deficiency. Four studies were made. The effects of dietary hexachloronaphthalene on preformed residual vitamin A, on assimilation of dietary carotene, on assimilation of a single oral dose of carotene, and on the absorption and storage of a single oral dose of vitamin A palmitate were investigated. In addition, the effect of ingested hexachloronaphthalene on calf plasma protein was studied. The following conclusions were derived from the results of the experiments. 1. The metabolism of dietary hexachloronaphthalene resulted in an increased requirement for vitamin A in peripheral tissue. This effect was apparently separate from the liver hypertrophy and fatty infiltration which are characteristic results of chlorinated naphthalene ingestion in rats. The mechanism of this increased demand for vitamin A was not discerned. Vitamin E supplementation was or no apparent value in preventing this increase in the requirement for vitamin A. 2. The addition of vitamin E to carotene-rich diets normally produces an increased yield of vitamin A. This stimulus of carotene conversion was not apparent when hexachloronaphthalene was included in the ration. 3. The ingestion of dietary hexachloronaphthalene depressed the ability of the rat to convert carotene to vitamin A. This was not true when the total dose of the toxic compound was included in the carotene solution. The addition of a bile salt to the carotene solution was not or value in preventing the depression of carotene conversion. Neither, however, did it stimulate conversion in the normal animals as was expected. 4. The ingestion of dietary hexachloronaphthalene had no apparent effect on the ability of the rat to absorb and store a single oral dose of vitamin A palmitate. 5. Paper electrophoresis studies and analysis of changes in TCA precipitable plasma protein in calves indicated that a depression of the level of the plasma proteins, especially the albumins, was a manifestation of the ingestion of hexachloronaphthalene by these animals. / Master of Science

Effects of developmental exposure to chlorpyrifos (CPS) or methyl parathion (MPS) on visuospatial, adaptive fear response, and passive avoidance memory and the signaling mechanisms responsible for these neurocognitive changes were investigated. Using an incremental low dose regimen, rat pups were orally gavaged daily with either corn oil (vehicle), CPS, or MPS from postnatal day 1 (PND1) -PND21. Cholinesterase activity was significantly inhibited with the highest dosages of CPS and MPS for up to 19 days after the last dosages. OP exposure impaired working and reference memory in males whereas in the females, enhancement occurred following CPS exposure. In addition, the adaptive fear response and passive avoidance retention memory was impaired in males whereas differential changes occurred in females. Accordingly, the behavioral deficits observed in males were persistent whereas the enhancement in females was transient. Males were more sensitive to OPs than females in that the medium and high dosages of CPS and MPS produced greater effects in females whereas all dosages of both compounds produced effects in males. Training in the radial arm maze significantly increased protein kinase C gamma (PKC ) expression and activity in the hippocampal membrane fraction of control rats whereas exposure to OPs exhibited a significant decrease in PKC and PKC immunoreactivity in both untrained and trained rats. However, MPS exposed females exhibited a significant increase in PKC expression in the cytosolic fraction but this was not related to improved memory. Reduction of membrane PKC expression and activity and cytosolic PKC expression and activity seemed to be related to visuospatial learning and memory deficits in exposed males but not exposed females. Brain-derived neurotrophic factor (BDNF) gene expression in the hippocampus was significantly increased (60%) in trained control males as compared to untrained control males. In contrast, trained and untrained females exhibited similar levels of BDNF gene expression. However, exposure of both sexes to either CPS or MPS significantly reduced the expression of BDNF in trained rats. In summary, these data indicate that OP exposure induced gender-specific changes in working memory formation and altered PKC isozyme levels/activity and BDNF expression.