Rat esophagus: Control vs. NMBA vs. Tocopherols
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE90464 | GEO | 2017/05/29
SECONDARY ACCESSION(S): PRJNA354714
REPOSITORIES: GEO
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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 short–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. Keywords: Toxicogenomics,reference design
2007-07-18 | GSE6917 | GEO
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.
2008-06-15 | E-GEOD-6917 | biostudies-arrayexpress
Project description:This microarray study was performed to investigate the molecular events in esophageal SCC carcinogenesis in NMBA induced rat esophageal SCC models.
2014-08-16 | GSE60439 | GEO
Project description:Our recent study (Reen et al., Cancer Res 2007;67:6484-92) identified 2261 dysregulated genes in the esophagi of rats that received a one week exposure to the carcinogen, N-Nitrosomethylbenzylamine (NMBA). We further reported that 1323 of these genes were positively modulated in the esophagus of NMBA-treated animals that also consumed dietary phenethyl isothiocyanate (PEITC), a constituent of cruciferous vegetables. Herein, we report our companion study wherein litter mate rats either received regular chow or chow with 5% freeze-dried black raspberries (BRB) for three weeks. During the third week one-half of these animals received three subcutaneous injections of NMBA (0.5 mg/kg body weight). All animals were sacrificed 24h after the last dose of NMBA, and their esophagi excised and processed for histological grading and RNA microarray profiling. Two hundred and fifty nine of the 2261 genes that were dysregulated by NMBA-alone were expressed at control levels in the esophagus of BRB-fed rats. Overall, the data indicate that a BRB diet has a genome-wide modulating effect on NMBA-caused dysregulation of gene expression in rat esophagus, including genes involved in phase I and phase II metabolism, oxidative damage, inflammation, differentiation, chromosome partitioning, cell adhesion, motility and cytoskeleton formation, and genes known to act as oncogenes and tumor suppressor genes regulating apoptosis, cell-cycling and proliferation, and angiogenesis. Keywords: Toxicogenomics, reference design.
2009-02-23 | GSE10623 | GEO
Project description:Transcriptome analysis of RNA samples from riboflavin deficiency combined with NMBA-induced rat esophageal intraepithelial neoplasia tissues. Epidemiological studies suggest that dietary riboflavin deficiency and environmental exposure to N-nitrosomethylbenzylamine (NMBA) are common in China's high incidence area of esophageal cancer. Riboflavin deficiency has been documented as an important risk factor for esophageal cancer. In this study, we established a F344 rat esophageal tumor model that combines dietary riboflavin deficiency with exposure to NMBA. The results showed that riboflavin deficiency combined with NMBA (R0N+) enhanced the incidence of esophageal intraepithelial neoplasia, including in situ carcinoma, whereas normal levels of riboflavin combined with NMBA (RcN+) mainly induced the occurrence of esophageal benign hyperplasia and small amount of esophageal intraepithelial neoplasia. Oxidative DNA damage (8-OHdG) and DNA double-strand breaks (p-γH2AX) in R0N+ rats were higher than that in RcN+ rats. The aim of the present study is to analyze the mechanism of riboflavin deficiency-induced tumorigenesis. So, we used Affymetrix Clariom D(also known as Rat Transcriptome Array 1.0) to identify genes that were differentially expressed upon R0N+ esophageal intraepithelial neoplasia tissues.
2018-02-28 | GSE111207 | GEO
Project description:This microarray study was performed to investigate the molecular events in esophageal SCC carcinogenesis in NMBA induced rat esophageal SCC models. Rats were housed 3 per cage under standard conditions: 20 ± 2ºC, 50±10% relative humidity, and 12 hours light/dark cycles. After two weeks of acclimation to the animal facility, the rats were administered s.c. injections of 0.2 ml of either NMBA (0.3 mg/kg body weight) or a 1:4 mixture of dimethyl sulfoxide (DMSO):H2O (the solvent for NMBA) 3 times per week for 5 weeks.
2014-08-16 | E-GEOD-60439 | biostudies-arrayexpress
Project description:Esophageal adenocarcinoma (EAC) has the fastest increase of any cancer in the US and Europe, and arises in the setting of BarrettM-bM-^@M-^Ys esophagus (BE), defined by replacement of normal squamous epithelium with columnar intestinal-like epithelium. BE is thought to result from chronic esophageal inflammation but has been elusive to model in animals. Herein, we have generated the first transgenic mouse model of BarrettM-bM-^@M-^Ys esophagus through overexpression of interleukin-1M-CM-^_ (IL-1M-NM-2). IL-1M-NM-2 overexpression in the mouse esophageal mucosa induces chronic inflammation that progresses to intestinal metaplasia, with characteristic expression of TFF2, Bmp4 and Cdx2. With aging, IL-1b transgenic mice progress to esophageal adenocarcinoma (EAC) but the process is markedly accelerated by exposure to bile acids and/or nitrosamines, resembling the human counterpart. Moreover, progenitor cells present in the gastric cardia, but absent from the esophagus in humans and mice, are increased in BE, suggesting the cell of origin in the gastric cardia Comparison of BE and EAC tissue from the mouse with normal squamous epithelium from the mouse.
2011-01-31 | E-GEOD-24931 | biostudies-arrayexpress
Project description:Barrett’s esophagus confers significant risk of esophageal adenocarcinoma. We have established the cloning of patient-matched stem cells of Barrett’s, gastric, and esophageal epithelium. Transplantation of transformed Barrett’s stem cells yielded tumors with hallmarks of esophageal adenocarcinoma, whereas transformed esophageal stem cells produced squamous cell carcinomas. These findings define a stem cell target in a precancerous lesion for preemptive therapies.
2015-10-01 | GSE64894 | GEO
Project description:Barrett’s esophagus confers significant risk of esophageal adenocarcinoma. We have established the cloning of patient-matched stem cells of Barrett’s, gastric, and esophageal epithelium. Barrett's esophagus stem cells (BE), gastric cardia stem cells (GC) and normal esophagus stem cells (Eso) from 12 patients were cloned (For BE: 12 patients, GC: 12 patients and Eso: 2 patients). Keratin 5 positive and Keratin 7 positive cells were cloned from human fetal esophageal epithelium. Using air liquid interface culture system, stem cells were induced to differentiate into mature epithelial structures.
2015-10-01 | GSE65013 | GEO
Project description:Esophageal adenocarcinoma (EAC) has the fastest increase of any cancer in the US and Europe, and arises in the setting of Barrett’s esophagus (BE), defined by replacement of normal squamous epithelium with columnar intestinal-like epithelium. BE is thought to result from chronic esophageal inflammation but has been elusive to model in animals. Herein, we have generated the first transgenic mouse model of Barrett’s esophagus through overexpression of interleukin-1ß (IL-1β). IL-1β overexpression in the mouse esophageal mucosa induces chronic inflammation that progresses to intestinal metaplasia, with characteristic expression of TFF2, Bmp4 and Cdx2. With aging, IL-1b transgenic mice progress to esophageal adenocarcinoma (EAC) but the process is markedly accelerated by exposure to bile acids and/or nitrosamines, resembling the human counterpart. Moreover, progenitor cells present in the gastric cardia, but absent from the esophagus in humans and mice, are increased in BE, suggesting the cell of origin in the gastric cardia
2011-01-31 | GSE24931 | GEO