title: Carcinogen-altered genes in rat esophagus positively modulated to normal levels of expression by both black raspberries and phenylethyl isothiocyanate.
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.
authors.affiliation: Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University College of Medicine, Columbus, Ohio 43240, USA. gary.stoner@osumc.edu
authors.forename: Gary D
authors.initials: GD
authors.lastname: Stoner
authors.forename: Alan A
authors.initials: AA
authors.lastname: Dombkowski
authors.forename: Rashmeet K
authors.initials: RK
authors.lastname: Reen
authors.forename: Daniela
authors.initials: D
authors.lastname: Cukovic
authors.forename: Sridevi
authors.initials: S
authors.lastname: Salagrama
authors.forename: Li-Shu
authors.initials: LS
authors.lastname: Wang
authors.forename: John F
authors.initials: JF
authors.lastname: Lechner
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002273:Carcinogens / Q000633:toxicity*; D004032:Diet; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives* / Q000633:toxicity; D004947:Esophagus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005638:Fruit; D005786:Gene Expression Regulation / Q000187:drug effects*; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D009389:Neovascularization, Pathologic / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000235:genetics
chemical_list: D002273:Carcinogens; D017879:Isothiocyanates; C058305:phenethyl isothiocyanate; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine