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Tni: Cnuaen. TuH lx(•. September 4, 1974 NlEMORAldDUM TO: Drs. Hockett, Huebner, Jacobson, Lynch, Nordsiek and Sommers FROM: W. U. Gardner SUBJECT: Application 1005. Irene Y. Wang, Ph.D., Cancer Research Institute, University of California, San Franri[-co. "Genetic Differences in tne In Vitro Metabolism of Chemical Carcinogens by Human and Mouse Tissues." This application must be considered in conjunction with the Rasmussen application. The applicant has been an ascistant of Dr. Rasmussen and is requesting one-half salary for the latter as welll as full salary for herself on this application. At the present time Dr. Rasmussen has a grant of $34,645.00 from c.'CR. Dr. Wana has a grant on a similar project from the Cancer Research Fund from the University of California for $13,290.00. It is a little unusual to have an associate request salary for a senior associats. Dr. Wang wants to look for genetic differences in BaP netabolites. So far the AHH studies have been on the 3-hydroxy BaP as the end point. nther arene oxidations may occur (NIH shift) and be followed by other hydroxylations. The microsomes of different tissues may produce different end products. The 450 cytochromes may also differ. In vitro studies on BaP metabolism as modified by cigarette smoke will be done. Human lymphocytes and surgica.l tissues will be similarly studied and the metabolite pattern of 3MC will he studied. The applicar.t has found the cyclohexene oxide is an inhibitor for the 4,5epoxide BaP, so that it accumulates in incubates of hamster liver microsomes. With suitable solvents it was possible to determine by chromato- graphy quinones, 3-OH-BaP and 3 dioles. They have found that PAH will induce AHH in rat liver and lung but that pl:enobarbital is effective only in the liver prepaiations and has different metabolic derivatives. They have noted that DBA mouse liver produces different metabolites than C57 and C3H. The several metabolic derivatives of human lymphocytes have been investigated in a preliminary way. The applicants have the methods worked out for the BaP system and plan to work on the metabolites of 3MC as well. They are now engaged in work of this general type. They have most of the instrumentation needed. I suggest a review by Gelboin, Kouri. This should he compared with the Bresnick apolication. W.U. G. WUG:ek