Phenethyl isothiocyanate inhibits nitrosamine carcinogenesis in a model for study of oral cancer chemoprevention

The anticarcinogenic effect of phenethyl isothiocyanate (PEITC) was examined in hamster buccal pouch mucosa exposed to N-nitrosomethylbenzylamine (NMBA). Unscheduled DNA synthesis (UDS) and induction of intraepithelial γ-glutamyl transpeptidase (γ-GT) histochemical foci were assessed as potential predictors of anticarcinogenicity. UDS mediated by in vitro exposure to NMBA (at 10 and 50 mM) was examined in mucosal samples derived following topical exposure of pouch mucosa to PEITC at concentrations of 0.5, 5, or 50 mM. In vivo PEITC pretreatment reduced NMBA-induced UDS in a dose dependent manner. PEITC treatment reduced induction of γ-GT foci, detected in epithelial wholemounts derived over a period of 8–13 weeks of NMBA application, by an average of 96%. PEITC also reduced tumor formation by 94%. γ-GT, in particular, may be a useful indicator for identification of effective oral cancer chemopreventive agents and combinations of agents.