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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.

SUBMITTER: Stoner GD

PROVIDER: S-EPMC3015106 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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

Stoner Gary D GD Dombkowski Alan A AA Reen Rashmeet K RK Cukovic Daniela D Salagrama Sridevi S Wang Li-Shu LS Lechner John F JF

Cancer research 20080801 15

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 ...[more]

PMID: 18676871

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Project description:To date, there is little information on early molecular events in the development of N-nitrosomethylbenzylamine (NMBA) induced esophageal tumorigenesis and of the effects of chemopreventive agents on these events. In this study, we identified genes in rat esophagus that were differentially expressed in response to shortâ??term NMBA-treatment and modulated by co-treatment with phenethylisothiocyanate (PEITC). Rats were fed AIN-76A diet or AIN-76A diet containing PEITC for three weeks. During the third week of dietary treatment, they were administered three s.c. doses of NMBA (0.5 mg/kg b.w.). Rats were sacrificed 24 h after the last treatment, esophagi excised and processed for histological grading, microarray and real-time PCR analysis. Our histopathological data showed that treatment of rats with PEITC had protective effect on NMBA-induced preneoplastic lesions in the rat esophagus. We identified 2261 genes that were differentially expressed in the NMBA-treated vs. control esophagi and 1936 genes in the NMBA+PEITC- vs. NMBA-treated esophagi. The intersection of these two sets resulted in the identification of 1323 genes in NMBA-treated esophagus that were modulated by PEITC to near-normal levels of expression. The measured changes in the expression levels of 10 selected genes were validated using real-time PCR. Principle components analysis (PCA) was applied to all twelve microarrays in the study, which suggested that in terms of global gene expression, PEITC treatment had a genome-wide modulating effect on NMBA-induced gene expression. Samples obtained from animals treated with PEITC alone or co-treated with NMBA were more similar to controls than they were to NMBA treatment alone. Experiment Overall Design: For each treatment we used a pooling strategy to enable the inclusion of samples from numerous animals. Three replicate microarrays were completed for each of the four treatments (control, PEITC, NMBA and NMBA+PEITC) for a total of twelve microarrays. Each microarray was hybridized using a pooled RNA sample, and each pool was created from equal amounts of total RNA from two or three independent RNA samples, representing individual animals. Each of these samples was obtained from a different animal, and no sample was included in more than one pool. In total, samples from nine animals per group were pooled for control, NMBA, PEITC and NMBA+PEITC microarrays. To facilitate comparisons of gene expression across all treatments, we utilized a reference design in which each microarray was co-hybridized with a common reference sample labeled with Cy3, and RNA from the treatment pool was labeled with Cy5. Stratageneâ??s Universal Rat reference RNA (Stratagene, La Jolla, CA) was used as the common reference in all microarrays.

Dataset Information

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

Publications

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

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