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

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.
AuthorsG D Stoner, C Adams, L A Kresty, S G Amin, D Desai, S S Hecht, S E Murphy, M A Morse
JournalCarcinogenesis (Carcinogenesis) Vol. 19 Issue 12 Pg. 2139-43 (Dec 1998) ISSN: 0143-3334 [Print] England
PMID9886569 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Anticarcinogenic Agents
  • Carcinogens
  • Isothiocyanates
  • Nitrosamines
  • 3-phenylpropyl isothiocyanate
  • nitrosobenzylmethylamine
  • Dimethylnitrosamine
  • N'-nitrosonornicotine
Topics
  • Animals
  • Anticarcinogenic Agents (therapeutic use)
  • Biotransformation
  • Carcinogens (metabolism, pharmacokinetics, toxicity)
  • Dimethylnitrosamine (analogs & derivatives, metabolism, pharmacokinetics, toxicity)
  • Esophageal Neoplasms (chemically induced, metabolism, prevention & control)
  • Esophagus (drug effects, metabolism)
  • Isothiocyanates (therapeutic use)
  • Male
  • Nitrosamines (metabolism, pharmacokinetics, toxicity)
  • Rats
  • Rats, Inbred F344

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