Effects of dietary phenethyl isothiocyanate, ellagic acid, sulindac and calcium on the induction and progression of N-nitrosomethylbenzylamine-induced esophageal carcinogenesis in rats

The potential inhibitory effects of phenethyl isothiocyanate (PEITC), ellagic acid (EA), sulindac and supplemental dietary calcium (SDC) on N-nitrosomethylbenzylamine (NMBA)-induced esophageal carcinogenesis were evaluated in rats utilizing an abbreviated (5 week) NMBA treatment protocol which allowed administration of the putative inhibitors throughout the experiment (i.e. beginning 2 weeks prior to NMBA treatment) or following completion of NMBA dosing only. PEITC at 500 p.p.m. significantly inhibited tumor incidence and multiplicity when given before and during, but not following, NMBA treatment. Neither sulindac at 125 p.p.m. nor SDC (2% versus 0.5% in control diet) inhibited tumor development when given during or following NMBA treatment. EA, which was administered only following NMBA treatment, significantly reduced the incidence (66.7% versus 100% in NMBA controls), but not the multiplicity, of esophageal tumors at the high-dose (4000 p.p.m.) level. Together these findings indicate that: (i) PEITC selectively inhibits the induction but not the subsequent progression of NMBA-induced esophageal tumors; (ii) EA may repress esophageal tumor development when administered following NMBA treatment; (iii) at the doses administered, neither sulindac nor SDC possess significant inhibitory activity against NMBA-induced esophageal carcinogenesis in the rat.