QUANTITATION OF BIOMARKERS OF OXIDATIVE STRESS BY NICI-MS

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In 1996 a workshop on Measurement of Oxidative Stress in Humans was held at NIEHS. There was a general consensus that it would be valuable to mount a study comparing various markers of oxidative stress measured from the same sample. One such marker is F2a-isoprostane which is quantitated by NICI-MS. Isoprostanes are prostaglandin-like compounds that are produced as a result of the chemical rather than enzymatic oxidation of arachidonic acid in membrane phospholipids. The isoprostanes have been shown to possess potent biological activity, and a number of studies have shown them to be accurate markers of lipid peroxidation in animal models of oxidative stress. The 8-iso-F2a- isoprostane has been the specific isomer quantified in most studies. Although there is recent evidence for some cyclooxygenase catalyzed formation of this compound, the contribution of the enzymatic pathway has appeared to be minor and primarily the result of oxidation of free lipid rather than membrane-bound lipid. The standard method for analyzing this compound is by GC/MS of the pentafluorobenzyl ester trimethylsilyl derivative under negative ion chemical ionization conditions. Our role in this study has been to establish methodology in-house for the measurement of isoprostanes in physiological samples and to provide this capability in collaboration with other groups at NIEHS/NIH. A number of other studies involving measurement of isoprostanes as an indicator of oxidative stress have also been initiated: 1)Womens Alcohol Study P. Taylor (NCI)/D. Baer, J. Judd (USDA; 2) Correlation of O.S. with mutations (T. Devereaux, LMC); identified mutations in chemically induced mouse hepatocellular adenomas and carcinomas - hypothesize mutations are the result of indirect DNA damage, possibly from O.S.; 3)Role of O.S. in lung tumor susceptibility (T. Devereaux/A. Patel)- correlate isoprostane/tumor production (in mice) as a function of age - Oxidative stress, isoprostanes, NICI-MS