Student Research: Alan Potter
, , 1993
Faculty Advisor: Terrance J. Kavanagh
The Effect of In Vivo Exposure to Phorone and Buthione Sulfoximine on Glutathione Content, Calcium Mobilization, and DNA Synthesis in Mouse Splenic T Lymphocytes
Toxicant exposure beneath some threshold level is often considered to pose little risk of producing any adverse effect. However, exposure to multiple toxicants, each beneath the level of concern, can lead to toxicity through a synergistic or additive action. This toxic integration can arise when the toxicants target the same tissue or organ. A common outcome from single or multiple exposures to any of a variety of toxicants can be the generation of oxidative stress. Oxidative stress generates peroxides, free radicals and reactive oxygen compounds, each able to damage crucial cellular components. Continued oxidative stress can jeopardize organ function and may eventually be lethal unless the cellular antioxidant mechanisms alleviate the stress. An important intracellular antioxidant is glutathione (GSH); it functions in detoxifying xenobiotics that induce oxidative stress, in removing reactive compounds produced from oxidative stress, and in reversing damage related to oxidative stress. Glutathione is also involved in immune system function, specifically with the ability of T cells to respond to mitogenic stimulation and to proliferate, events of paramount importance in immunity. Excessive oxidative stress can overwhelm glutathione synthesis and redox cycling, leading to glutathione depletion. It is speculated here that when the immune system has been the toxicant target, the associated glutathione depletion compromises T lymphocyte function. Continual oxidative stress could chronically depress the immune system thereby increasing susceptibility to infection, autoimmunity, allergy, and neoplasia.
It is the hypothesis of this thesis that in vivo depletion of glutathione in T lymphocytes will correlate with in vitro alterations in lymphocyte signal transduction capability and proliferative capacity.
Taken from the beginning of thesis.