Mechanism of enhancement of esophageal tumorigenesis by 6-phenylhexyl isothiocyanate

Mark A. Morse, Lu Jerry, Rajaram Gopalakrishnan, Lisa A. Peterson, Gulzar Wani, Gary D. Stoner

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21 Scopus citations


6-Phenylhexyl isothiocyanate (PHITC) enhances esophageal tumorigenesis induced by the carcinogen N-nitrosomethylbenzylamine (NMBA) in rats while its shorter chain analog, phenethyl isothiocyanate (PEITC), inhibits NMBA-induced esophageal tumorigenesis. A significant increase in O6-methylguanine levels in esophageal DNA at 72 h after NMBA administration to rats pretreated with PHITC suggested that PHITC might enhance NMBA metabolic activation or inhibit DNA repair. To test this hypothesis, groups of 20 rats were administered PEITC or PHITC at concentrations of 0, 1.0, or 2.5 mmol/kg in modified AIN-76A diet for 2 weeks. The esophagi were removed from rats, stripped, split, and maintained in HEPES buffered saline (HBS) for assays of NMBA metabolism (n = 5 per group) or were snap frozen for DNA repair assays (n = 15 per group). The principal metabolites of NMBA produced by esophageal explants were: two unidentified peaks, benzyl alcohol (at 4 h only), and benzoic acid. Esophageal explants from PEITC-treated animals showed a significantly decreased ability to metabolize NMBA as expected. PHITC-treated animals showed a slight inhibition in the formation of most NMBA-related metabolites, rather than an overall increase in NMBA activation. This inhibition was less than that observed with PEITC. No inhibitory effects were observed on O6-alkylguanine transferase (AGT) activity in the esophagi of rats treated with 1.0 μmol/g or 2.5 μmol/g PHITC. Thus, effects of PHITC on esophageal metabolism and DNA repair do not account for the enhancement of NMBA tumorigenicity by PHITC.

Original languageEnglish (US)
Pages (from-to)119-125
Number of pages7
JournalCancer Letters
Issue number1
StatePublished - Jan 15 1997

Bibliographical note

Funding Information:
Supported by NIH grants CA-46535 59887.


  • Esophagus
  • N-Nitrosomethylbenzylamine
  • Phenethyl isothiocyanate
  • Phenylhexyl isothiocyanate

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