Gd. Stoner et al., Inhibition of N '-nitrosonornicotine-induced esophageal tumorigenesis by 3-phenylpropyl isothiocyanate, CARCINOGENE, 19(12), 1998, pp. 2139-2143
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.