Document xzkMBQBaDg1b3mELrp0Z82ewJ

The Sehod of Public Health Department of Environmental Science* and En^ineerim THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL Tht Uiuvcruiy of Nonh CtroUn* ( Qupd Hill CBI UOO, Rmuiu HtH Chtpd Hill. NjC. J75W-*400 October 19,1994 Dr. Hasmukh C. Shah Manager, Vinyl Chloride Panel Chemical Manufacturers Association 2501 M Street, NW Washington, D.C. 20037 Dear Dr. Shah: I enjoyed seeing you at the CUT Open House last week. This letter is a follow up to our conversation regarding the discussions that the Vinyl Chloride Panel held following our visit to the EPA. I would be interested in working with you on some of the issues that are still of concern such as determining the of the ethenoguanine DNA adduct (EG), and quantitating the amount of the methyl purine DNA glycosylase (MPG) and P450 2E1 in tissues ofhumans of different ages. We discussed the approach that I would use to determine the Tm of EG. This would require the synthesis of [13Cj-vinyl chloride. I would then expose groups of 3-4 rats using the closed chamber technique to the stable isotope and sacrifice them at different times (0,4,12, and 24 hours) after a 6 hour exposure to -1000 ppm VC. This would be repeated several times to determine the average Tia of EG using our GC/ high resolution MS methodology. Dr. Johannes Filser will visit me next week and X plan on discussing the details of the animal exposure with him, as he is an expert in the closed chamber technique. We are just setting up a quantitative polymerase chain reaction (PCR) method for measuring the expression of the MPG DNA repair protein. We plan to evaluate age difference^ in rats and mice under our Superfund Basic Research Program proposal, providing it gets funded. What I hadn't considered until I met with the VC Panel was doing this in human tissues of different ages. This may require slight adjustments in methodology and the synthesis of different primers. I believe that 1 can obtain human tissues from various tissue banks such as Vanderbilt University and the University of R&S 147705 Maryland. It rray also be possible to get them from UNC and Duke. Yon indicated a desire to also examine P450 2E1 expression in similar tissue. I would probably ask Dr. Fred Guengeiich to collaborate on this aspect. He has afi of the methods in place and could use the same tissue specimens that we use for MPG. ( These studies would be modest in size and scope, but should provide very important information relevant to human risks associated with vinyl chloride exposure. The direct cost of this research would be ~ $50,000 per year for two years, with half of this for the DNA adduct studies, 35% for the MPG determinations and 15% for the P450 2E1 studies. If this is handled as a grant to the university, there would be 44.5% overhead charged on the direct costs. If it is provided as a gift, there is no overhead. If a grant is desired, I will need to submit a research proposal and budget for university approval. I hope this provides enough information for your next year's budget meeting. We can obviously increase or decrease the effort if this is deemed to little or to great Please let me know what the Panel decides. Thank you again for your interest in our research. Sincerely, James A. Swenberg, D.V.M., Ph.D. Director, Curriculum in Toxicology Professor* Environmental Sciences and . Engineering, and Pathology