Higher incidence of cancer among blacks is a major problem in this country and its cause is unknown. The proposed study attempts to discover the cause which may be related to a dietary factor. The hypothesis to be investigated is that phenol and 2,6-dimethoxyphenol (syringol), the two major phenolic components of smoked meats, inhibit the N- nitrosoproline (NPRO) formation in vitro and in vivo in rats from precursors L-proline and nitrite. NPRO formation in vivo is considered to be a measure of nitrosation in the animal system. It is intended to determine whether the smoked meats are the scavengers of added nitrite and are thus the potential inhibitors of the carcinogenic N-nitrosamine formation in vivo. In six duplicate in vitro experiments (each to be conducted with and without a simulated gastric fluid), aqueous mixtures of prokine 500 muM, a modified (phenol(0 or 500 muM;) syringol (0 or 500 muM); phenol0 or 234 muM)+syringol (0 or 500 muM); a phenolic extract derived from a smoked meat (0 or optimum concentration); an extract derived from a non-smoked meat (of weight similar to that of smoked meat) and nitrite (1000 muM) will be incubated for 30 min at 37degreesC and pH 3.0, 4.5 and 6.0. The reaction mixture will be extracted with ethyl acetate, the extract concentrated to dryness, and analyzed with HPLC to determine the NPRO concentration. In six duplicate in vivo experiments, the concentration and pH of the aqueous mixtures of precursors and a modifier to be administered to rats by gavage, will be the same as used in the in vitro experiments. The 24 h rat urine and feces will be collected, processed, and analyzed for NPRO content as described above. The results in the two systems would indicate (a) whether the two phenols are inhibitors of NPRO formation (b) whether there is a general agreement between them (c) whether the smoked meats are inhibitors of NPRO formation and thus could cause reduction of human exposure to endogenous carcinogenic N-nitrosamines. Two minority students (1 Sophomore and 1 Junior) each year will receive training in the laboratory techniques and the principal investigator will gain experience in the biomedical research under the proposed project.
