We propose to investigate the effects of ozone exposure on: (i) antioxidant defense mechanisms; (ii) lipid peroxidation potential; (iii) the levels of prostaglandins, prostacyclins, thromboxanes, and leukotriens; (iv) the activities of enzymes involved in the metabolism of arachidonic acid; and (v) the cooxidation of procarcinogens by prostaglandin synthetase in the rat lung under conditions of dietary vitamin E deficiency, selenium deficiency, and a combination of both. The hypothesis to be tested is: uncontrolled lipid peroxidation, a potential consequence of oxidant stress exacerbated by inadequate vitamin E and selenium nutrition, can lead to damage of pulmonary cells via perturbation of membrane systems and lung metabolic functions. In view of the potential detrimental effects of ozone exposure under conditions of antioxidant deficiency, both in vivo and in vitro procedures will be utilized to evaluate the susceptibility of lung membrane systems to lipid peroxidation and the response of lung tissue to insult from potential mutagenic/carcinogenic agents resulting from oxidative metabolism of polycyclic aromatic hydrocarbons, and to identify and quantify the prostaglandin-like endoperoxides formed during peroxidation of polyunsaturated fatty acids. The research methods to be employed include thin-layer and high pressure liquid and gas chromatographic techniques for the analysis of arachidonic acid metabolites, polarographic and spectrophotometric methods for analysis of enzymic activity, and liquid scintillation spectrometry. From the information obtained in these studies insight will be gained concerning the mechanism(s) by which vitamin E and selenium modulate arachidonic acid metabolism and protect against oxidant stress.
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