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.
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Authors | G D Stoner, C Adams, L A Kresty, S G Amin, D Desai, S S Hecht, S E Murphy, M A Morse |
Journal | Carcinogenesis
(Carcinogenesis)
Vol. 19
Issue 12
Pg. 2139-43
(Dec 1998)
ISSN: 0143-3334 [Print] England |
PMID | 9886569
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Anticarcinogenic Agents
- Carcinogens
- Isothiocyanates
- Nitrosamines
- 3-phenylpropyl isothiocyanate
- nitrosobenzylmethylamine
- Dimethylnitrosamine
- N'-nitrosonornicotine
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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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