We study oxidative stress (the stress that oxidants place on organisms) and the way organisms cope with this stress. Because environmental toxins often increase oxidative stress, many of our studies are relevant to toxicology. Since the antioxidant vitamins (such as vitamins E and C) help organisms cope with stress, we also study the effects of these vitamins.
Ozone, the most powerful oxidant in smog, is one of the most important toxins worldwide. We are measuring the rates of the reactions and the products formed when ozone reacts with the biological target molecules it encounters when it enters the lung. These target molecules include olefins (such as the unsaturated fatty acids), thiols (such as glutathione), and reducing agents (such as vitamins E and C). We have shown that lipid ozonation products (LOP) are one of the major ozonation products in the lung and that these LOP act as messenger molecules, signalling a cascade of physiological effects including inflammation (known to result from breathing ozone). We demonstrated that some of the principal LOP formed in model systems act as signal transduction molecules in pulmonary epithelial cell culture systems.
We also are studying nitrogen oxide. Paradoxically, nitrogen oxide is a toxin that occurs in smog but also is produced by a number of cell types and used as a hormone and signal transduction molecule. In particular, we study the reactions of nitric oxide with superoxide; both these species are free radicals and they combine at a near-diffusion controlled rate. Peroxynitrite is a potent, although quite selective oxidant, whereas, neither nitric oxide nor superoxide are oxidants. Thus, the production of peroxynitrite both modulates the levels of NO and superoxide in a cell and also converts these two non-oxidants to a potent oxidizing species.
We have been studying the free radical chemistry of cigarette tar and urban soot for a number of years. We were the first to identify the stable radical present in cigarette tar as a semiquinone; this semiquinone reduces oxygen to make superoxide, and, from that, the hydroxyl radical. Superoxide-generating systems are known to cut ("nick") DNA, and we have shown that the free radical in cigarette tar solutions both binds to DNA and then nicks the DNA. We have now found that very fine, combustion-generated particulate matter, called PM2.5, also contains a similar radical and similarly damages DNA. The EPA has just set stringent new regulations for PM2.5. While PM2.5 is known to pose a health hazard, the mechanism(s) of the damage caused to lung tissue is not known. We are exploring the hypothesis that the radicals in PM2.5 are involved in the damage caused to the lung.
Selected Publications
W. A. Pryor. Vitamin E and heart disease: "Basic science to clinical intervention trials," Free Radical Biol.Med., 2000, 28 (1), 141-164.
R. M. Kafoury, W. A. Pryor, G. L. Squadrito, M. G. Salgo, X. Zou, and M. Friedman. "Introduction of inflammatory mediators in human airway epithelial cells by lipid ozonation products," Am. J. Respir. Crit. Care Med., 1999, 160, 1934-1942.
M. W. Frampton, W. A. Pryor, R. Cueto, C. Cox, P. E. Morrow, and M. J. Utell. "Ozone exposure increases aldehydes in epithelial lining fluid in human lung," Am. J. Respir. Crit. Care Med., 1999, 159, 1134-1137.
G. J. Handelman and W. A. Pryor. "Evaluation of antioxidant status in humans," In: Antioxidants in Nutrition and Health, edited by A. Papas,CRC Press, 1999, 37-62
D. Hwang, P. Chanmugam, M. Boudreau, K. H. Sohn, K. Stone, and W. A. Pryor. "Activation and inactivation of cyclo-oxygenase in rat alveolar macrophages by aqueous cigarette tar extracts," Free Radic. Biol. Med., 1999, 27 (5/6), 673-682.