Mechanism of enhancement of esophageal tumorigenesis by 6-phenylhexyl isothiocyanate.

Published

Journal Article

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 micromol/g or 2.5 micromol/g PHITC. Thus, effects of PHITC on esophageal metabolism and DNA repair do not account for the enhancement of NMBA tumorigenicity by PHITC.

Full Text

Cited Authors

  • Morse, MA; Lu, J; Gopalakrishnan, R; Peterson, LA; D'Ambrosio, SM; Wani, G; Stoner, GD

Published Date

  • January 1997

Published In

Volume / Issue

  • 112 / 1

Start / End Page

  • 119 - 125

PubMed ID

  • 9029177

Pubmed Central ID

  • 9029177

Electronic International Standard Serial Number (EISSN)

  • 1872-7980

International Standard Serial Number (ISSN)

  • 0304-3835

Digital Object Identifier (DOI)

  • 10.1016/s0304-3835(96)04556-9

Language

  • eng