Data from this laboratory has shown that the level of nicotinamide in the diet can influence N-nitrosodimethylamine carcinogenesis in albino rats. The objective of this study is to continue this research on the use of dietary nicotinamide as a modifier of tumorigenic risk and to determine the molecular events that connect this vitamin to the action of carcinogens. The carcinogen that will be utilized for this nutritional study on tumorigenesis is 9,10-dimethyl-1,2-benzanthracene, DMBA. The tumor model is submandibular salivary gland carcinomas and the animal model is Sprague-Dawley rats. The rats will be separated into five groups and placed on one of four special diets. The diets will contain differing amounts of nicotinamide and/or an inhibitor of poly(ADP-ribose) polymerase. Poly(ADP-ribose) polymerase is a nuclear enzyme that uses NAD as a substrate. This enzyme appears to have a function in DNA repair and may be the underlying metabolic reason linking dietary nicotinamide to carcinogenesis. After the rats are established on the diets, four of the five groups will be challenged with the carcinogen. Pellets containing 0.75 mg of DMBA will be surgically implanted in the submandibular glands. The control group will receive a pellet of beeswax. The animals will remain on the four special diets for twelve additional weeks. After this period of time all of the rats will be given Purina Rat Chow. Twenty-five weeks after the implant of the pellets the rats will be sacrificed. Autopsies will be performed to determine the incidence of salivary gland tumors. The size and weight of the tumors will be recorded and sections from the neoplasms and normal glands will be taken for histological examination. The data from the different groups will be compiled and compared statistically to determine the effect of each diet on DMBA-induced carcinogenesis. Throughout the course of the experiment, a number of auxiliary studies will be performed. These additional experiments will measure the effects of the carcinogen and the special diets on the metabolism of NAD-NADH, NADp-NADPH, and poly(ADP-ribose). Through the use of this data plus the data on tumor incidence, it may be possible to define the cellular mechanism or mechanisms that link dietary nicotinamide to carcinogenesis.
