Carcinogen-altered genes in rat esophagus positively modulated to normal levels of expression by both black raspberries and phenylethyl isothiocyanate

Cancer Res. 2008 Aug 1;68(15):6460-7. doi: 10.1158/0008-5472.CAN-08-0146.

Abstract

Our recent study identified 2,261 dysregulated genes in the esophagi of rats that received a 1-week exposure to the carcinogen N-nitrosomethylbenzylamine (NMBA). We further reported that 1,323 of these genes were positively modulated to near-normal levels of expression in NMBA-treated animals that consumed dietary phenylethyl isothiocyanate (PEITC), a constituent of cruciferous vegetables. Herein, we report our results with companion animals that were fed a diet containing 5% freeze-dried black raspberries (BRB) instead of PEITC. We found that 462 of the 2,261 NMBA-dysregulated genes in rat esophagus were restored to near-normal levels of expression by BRB. Further, we have identified 53 NMBA-dysregulated genes that are positively modulated by both PEITC and BRB. These 53 common genes include genes involved in phase I and II metabolism, oxidative damage, and oncogenes and tumor suppressor genes that regulate apoptosis, cell cycling, and angiogenesis. Because both PEITC and BRB maintain near-normal levels of expression of these 53 genes, their dysregulation during the early phase of NMBA-induced esophageal cancer may be especially important in the genesis of the disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Carcinogens / toxicity*
  • Diet
  • Dimethylnitrosamine / analogs & derivatives*
  • Dimethylnitrosamine / toxicity
  • Esophagus / drug effects*
  • Esophagus / metabolism
  • Esophagus / pathology
  • Fruit*
  • Gene Expression Regulation / drug effects*
  • Isothiocyanates / pharmacology*
  • Male
  • Neovascularization, Pathologic / genetics
  • Rats
  • Rats, Inbred F344
  • Signal Transduction / genetics

Substances

  • Carcinogens
  • Isothiocyanates
  • phenethyl isothiocyanate
  • nitrosobenzylmethylamine
  • Dimethylnitrosamine