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

Carcinogenesis. 1998 Dec;19(12):2139-43. doi: 10.1093/carcin/19.12.2139.

Abstract

The ability of dietary isothiocyanates to inhibit the esophageal metabolism of N'-nitrosonornicotine (NNN) was examined in F344 rats. Following feeding of benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC), 3-phenylpropyl isothiocyanate (PPITC), 4-phenylbutyl isothiocyanate (PBITC) or 6-phenylhexyl isothiocyanate for 2 weeks, rats were killed and the esophagi were incubated in vitro with [5-3H]NNN. While dietary BITC, PEITC and PBITC all decreased NNN metabolism, dietary PPITC had the greatest effect, yielding 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 micromol/g PPITC and were given untreated drinking water or drinking water containing 5 p.p.m. NNN. After 87 weeks, the experiment was terminated and the esophageal tumors were counted. Rats that were given untreated 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 PPITC reduced the incidence and multiplicity of NNN-induced esophageal tumors by >95%. These results demonstrate the remarkable chemopreventive efficacy of PPITC in the NNN-induced esophageal tumor model.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anticarcinogenic Agents / therapeutic use*
  • Biotransformation
  • Carcinogens / metabolism*
  • Carcinogens / pharmacokinetics
  • Carcinogens / toxicity
  • Dimethylnitrosamine / analogs & derivatives
  • Dimethylnitrosamine / metabolism
  • Dimethylnitrosamine / pharmacokinetics
  • Dimethylnitrosamine / toxicity
  • Esophageal Neoplasms / chemically induced
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / prevention & control*
  • Esophagus / drug effects*
  • Esophagus / metabolism*
  • Isothiocyanates / therapeutic use*
  • Male
  • Nitrosamines / metabolism*
  • Nitrosamines / pharmacokinetics
  • Nitrosamines / toxicity
  • Rats
  • Rats, Inbred F344

Substances

  • Anticarcinogenic Agents
  • Carcinogens
  • Isothiocyanates
  • Nitrosamines
  • 3-phenylpropyl isothiocyanate
  • nitrosobenzylmethylamine
  • Dimethylnitrosamine
  • N'-nitrosonornicotine