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 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.
Stoner
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GD
Division of Environmental Health Sciences, The Ohio State University School of Public Health and The Ohio State University Comprehensive Cancer Center, Ohio State University, CHRI, Columbus 43210, USA. stoner.21@osu.edu
Adams
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C
Kresty
L A
LA
Amin
S G
SG
Desai
D
D
Hecht
S S
SS
Murphy
S E
SE
Morse
M A
MA
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D004947:Esophagus / Q000187:drug effects* / Q000378:metabolism*; D017879:Isothiocyanates / Q000627:therapeutic use*; D008297:Male; D009602:Nitrosamines / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D017879:Isothiocyanates; D009602:Nitrosamines; C093849:3-phenylpropyl isothiocyanate; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine; C008655:N'-nitrosonornicotine