Document gbBgB1Nzr8064pNQqO05wbGY3

The School of Public Health Oepertment of Environmental Science* and Enjineehiu THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL The Univ^rwy of North Cwrolin* t Chapd Hill CBi 7400, JUnaunt Hall Chapd Hili, Nr. nm-in 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: 1 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. 1 would be interested in working with you on some of the issues that are still of concern such as determining the T1/2 of the etbenoguanine DNA adduct (EG), and quantitating the amount of the methyl purine DNA glycosylase (MPG) and P450 2E1 in tissues of humans of different ages. We discussed the approach that I would use to determine the Tw of EG. This would require the synthesis of [13CJ-vjnyl chloride. I would then expose groups of 3-4 rats using the closed chamber technique to the stable isotope and sacrifice them at different tunes (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 Tw of EG using our GC/ high resolution MS methodology. Dr. Johannes Filser will visit me next week and I 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 differences 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 m methodology and the synthesis of different primers. I believe that I can obtain human tissues from various tissue banks such as Vanderbilt University and the University of R&S152188 Maryland. It rray also be possible to get them from UNC and Duke. You indicated a desire to also examine P450 2E1 expression in similar tissue. I would probably ask Dr. Fred Guengerich to collaborate on this aspect He has al of the methods in place and could use the same tissue specimens that we use for MPG. t 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% fw the MPG determinations and 15% for the P4502E1 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 die Panel decides. Thank you again for your interest in our research. Sincerely, James A. Swenberg, D.VJM, Ph.D. Director, Curriculum in Toxicology Professor, Environmental Sciences and . Engineering, and Pathology 69l5sisy