Collaborative Projects In Environmental Health Sciences

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Summary of Work: This project includes those endeavors in which the mass spectrometry workgroup collaborates with other groups, both inside and outside the Institute to solve problems of mutual interest. The major focuses of these projects are: 1) structure determination of unknown compounds; 2) identification and/or confirmation of biological pathways; 3) quantitation; and 4) development of strategies for the analysis of biologically important compounds. Not included in this project are the many analyses performed on a strictly service basis. We continue to collaborate with D. Zeldin, LPP, on the identification and quantitation of arachidonic acid metabolites in physiological samples by selected ion monitoring (SIM) under negative ion chemical ionization (NICI) mass spectrometry. The products of enzymatically induced arachidonic acid oxidation, epoxyeicosatrienoic acids (EETs) and hydroxyeicosatrienoic acids (HETEs), exhibit significant biological effects, both harmful and beneficial. The characterization of the enzymes involved in the oxidation process and location of the enzymes is important in understanding the functional significance of the enzymes. Additionally, the response of the enzymes involved with arachidonic acid metabolism to environmental challenges may be a significant factor/indicator of environmentally induced disorders. We have characterized the epoxyeicosatrienoic acids formed by new P450s, CYP2J9, found in mouse brain This enzyme was observed to metabolize arachidonic acid to 19-hydroxyeicosatetraenoic acid distingusihing it form other P450s. It was found to be loacalized to cerebellar Purkinje cells, and active in 19-HETE formation, an eicosanoid that inhibits activity of P/Q-type Ca channels. Epoxyeicosatrienoic acids possess fribrinolytic properties through induction of tissue plasminogen activaotr and may play a role in regulating vascular hemostasis. With C. Chignell, LPC, we are analyzing DNA that has been subjected to UVA and UVB radiation in the presence and absence of the antibiotic lumifloxicin.