The hypothesis to be tested in this proposal is that inhalation exposure to environmental oxidants produces pulmonary metabolism and epithelial injury and turnover. Sufficient preliminary information will be generated so that a comprehensive assessment of this hypothesis can be formulated in a future grant application. The proposed studies will: (a) quantify the effect of ozone exposure across concentration and time in damage in nuclear and mitochondrial DNA of epithelial cells and macrophages, distribution and extent of acute epithelial injury, and oxidative stress and conventional markers of injury. (b) A determination will be made whether the enhanced oxidant susceptibility results in greater expression of the putative biomarker (mitochondrial DNA damage) using a mitochondria-specific, antioxidant-comprimised animal model (MnSOD heterozygotes; +/-). Two exposures and durations will be tested. An interdisciplinary approach combined with a new interdepartmental collaboration will be applied. These preliminary results will establish novel associations among indices of cellular injury and exposure to environmental oxidants and will supply supporting evidence for the use of mitochondrial DNA damage as a biomarker, a measure of exposure and susceptibility to environmental oxidants.
