Carcinogen-altered genes in rat esophagus positively modulated to normal levels of expression by both black raspberries and phenylethyl isothiocyanate.
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.
Stoner
Gary D
GD
Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University College of Medicine, Columbus, Ohio 43240, USA. gary.stoner@osumc.edu
Dombkowski
Alan A
AA
Reen
Rashmeet K
RK
Cukovic
Daniela
D
Salagrama
Sridevi
S
Wang
Li-Shu
LS
Lechner
John F
JF
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
D002273:Carcinogens; D017879:Isothiocyanates; C058305:phenethyl isothiocyanate; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine