Our ongoing studies have clearly shown that arylalkyl isothiocyanates are potent inhibitors of nitrosamine carcinogenesis. The overall goal of this program is to extend our findings by carrying out further bioassays and mechanistic studies of chemoprevention by isothiocyanates in rats and mice, and to examine the effects of isothiocyanates on nitrosamine metabolic activation in the Patas monkey and in humans.
The specific aims of this program are: 1) carry out bioassays of dietary phenethyl isothiocyanate (PEITC) and 6-phenylhexyl isothiocyanate (PHITC) as inhibitors of lung and pancreatic cancer induced in F344 rats by chronic oral administration of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK), and of PEITC and 4-phenylbutyl isothiocyanate (PBITC) as inhibitors of esophageal cancer induced in F344 rats by chronic oral administration of another tobacco-specific nitrosamine, N'- nitrosonornicotine (NNN); 2) investigate the cellular specificity of PEITC inhibition of NNK-DNA binding in rat lung; 3) determine the effects of PEITC and PHITC on the metabolism of NNN and NNK in the Patas monkey; 4) in collaboration with Program 2, investigate the effects of PEITC and PHITC on the metabolism of NNK in cultured explants of human lung; 5) in collaboration with Program 1, determine the effects of watercress, garden cress, and mustard on NNK/NNN hemoglobin adducts in smokers; 6) investigate the effects of PEITC and benzyl isothiocyanate (BITC) on the tumorigenicity and metabolic activation of benzo(a)pyrene in A/J mice. The results of these studies will advance our overall goal of evaluating the potential of isothiocyanates as chemopreventive agents for human cancer.
