Inhibition of N '-nitrosonornicotine-induced esophageal tumorigenesis by 3-phenylpropyl isothiocyanate

The ability of dietary isothiocyanates to inhibit the esophageal metabolism of N'-nitrosonornicotine (NNN) was examined in F344 rats. Following feedin g of benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC), 3-phen ylpropyl isothiocyanate (PPITC), 4-phenylbutyl isothiocyanate (PBITC) or 6- phenylhexyl isothiocyanate for 2 weeks, rats were killed and the esophagi w ere incubated in vitro with [5-H-3]NNN. While dietary BITC, PEITC and PBITC all decreased NNN metabolism, dietary PPITC had the greatest effect, yield ing inhibition ranging from 55 to 91% of the control production of various NNN metabolites. To determine the chemopreventive efficacy of PPITC on NNN- induced esophageal tumorigenesis, rats were fed AIN-76A diets containing 0, 1.0 or 2.5 mu mol/g PPITC and were given untreated drinking water or drink ing water containing 5 p,p,m, NNN, After 87 weeks, the experiment was termi nated and the esophageal tumors were counted. Rats that were given untreate d drinking water developed no tumors. Rats that were given 5 p,p,m, NNN and unadulterated AIN-76A diet had an esophageal tumor incidence of 71% and a multiplicity of 1.57 tumors/ animal. The two dietary concentrations of PPIT C reduced the incidence and multiplicity of NNN-induced esophageal tumors b y >95%, These results demonstrate the remarkable chemopreventive efficacy o f PPITC in the NNN-induced esophageal tumor model.