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. ~;.. T-Ar•. -CbUxcri, FoR ToBACCO REsE AKCx-U.S.A., INc. January 24, 1977 MIORANDUM J T0: Drs. Hockett, Huebner, Jacobson, Sommers and Stone FROMc W. U. Gardner HK®1723011 SUB.7ECT: Application 966-A. Nathan H. Sloane, Ph.D., Department of Biochemistry, Center for the Health Sciences, University of Tennessee, Memphis. "Effect of Benzo(a)pyrene and Derivatives on Mammalian Lung Cellq." The aims of this investigation area (1) to purify and determine the composition of the 5-hydroxymethyl synthetase. Studies so far show that it contains both a protein and a lipid fraction, (2) study the possible tsaxlsfor.nation of cultured lung cells from a numabe of species by BaP and its metabolites especially those derived by non-hydroxylative processes, and (3) use 3H PAHs determine their binding to transformation-susceptible and resistant cell lines. The HMBaPSase seems to be rather uniquely a lung enzyme. The lipid C-1 Component used is obtained froia bovine lung and the apoenzyme from rat lung. Transformation will be attempted in mouse and har,ster cells in culture, sometimes in the presence of P-450 inhibitors and in the presence of a-naphthoflavone, an AHH i'.nhi.bitor. Tiie covalent binding of BaP to cultured cells with or without the presence of different inhibitors will be studied. Bidning with other nuclear constituents will be determined. Some col'iabo:ative genetic studies Dr. MPier are also planned. At the present time Dr. Sloane has a CTR grant and a small graniL from the ACS. The cur;ent request is for approximately the sume of these two current grants. He does have pend_ng applications with th(c ACS and NCI. He is now asking for th_ aalaries of a postdoctorai person and a technician: and $6,000 for expendables and publications costs. Should other grants be approved the budget will be revised. He is asking for three-years st(pport. He has already had two years. One year was spent with Dr. Amos at Harvard. Dr. Boutwell might be an ad hoc consultant. W.U.G. WUG:ek