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Effects of a black raspberry diet on gene expression in the rat esophagus
John F Lechner1, Rashmeet K Reen, Alan A Dombkowski
1Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
Abstract:
A diet containing 5% freeze-dried black raspberries (BRB) markedly inhibits esophageal cancer in rats treated with the carcinogen, N-Nitrosomethylbenzylamine (NMBA). We previously identified esophageal genes that become dysregulated after short-term treatment of rats with NMBA and determined which genes are maintained at near-normal levels of expression if the animals were fed 5% BRB prior to and during NMBA treatment. In this study, we report the effects of the BRB diet on gene expression in esophagi from untreated (control) animals. After 3 wk on a 5% BRB diet, control esophagi were excised, stripped of the submucosal and muscularis layers, and processed for histology and microarray profiling. RNA microarrays revealed that the BRB altered the expression levels of 36 genes; 24 were upregulated, and 12 were downregulated. Among the upregulated genes are genes associated with cellular matrix, signaling cascades, transcription regulation, apoptosis, metabolism, and intriguingly, contraction. Most of the downregulated transcripts are involved in cell regulation, signal transduction, and metabolism. Histopathological analyses revealed that the BRB have little or no effect on esophageal morphology. In conclusion, histological and molecular studies indicate that a 5% BRB diet produces only modest effects on the esophagus, the target tissue for NMBA carcinogenesis in the rat.
Insights
Black raspberries (BRB) show modest effects on rat esophagus gene expression. This research explores how BRB impacts normal esophageal tissue molecular profiles without carcinogen exposure.
Area of Science:
- Oncology
- Nutritional Science
- Molecular Biology
Background:
- Esophageal cancer is a significant health concern.
- N-Nitrosomethylbenzylamine (NMBA) is a known carcinogen used to induce esophageal cancer in rat models.
- Previous studies indicated that black raspberries (BRB) inhibit NMBA-induced esophageal cancer.
Purpose of the Study:
- To investigate the effects of a 5% black raspberry (BRB) diet on gene expression in the normal rat esophagus.
- To identify specific genes and pathways modulated by BRB in the absence of carcinogen exposure.
- To understand the baseline molecular changes in the esophagus induced by BRB.
Main Methods:
- Rats were fed a diet containing 5% freeze-dried black raspberries (BRB) for 3 weeks.
- Esophageal tissues were collected, processed for histology, and subjected to microarray profiling.
- Gene expression analysis was performed using RNA microarrays.
Main Results:
- The BRB diet altered the expression of 36 genes in the normal rat esophagus (24 upregulated, 12 downregulated).
- Upregulated genes were associated with cellular matrix, signaling, transcription, apoptosis, metabolism, and muscle contraction.
- Downregulated genes were primarily involved in cell regulation, signal transduction, and metabolism.
- Histological analysis showed minimal effects of BRB on esophageal morphology.
Conclusions:
- A 5% BRB diet induces modest molecular changes in the rat esophagus.
- These findings provide baseline molecular data for BRB's effects on the target tissue of NMBA carcinogenesis.
- BRB's cancer-inhibitory effects may involve subtle modulations of normal esophageal gene expression.
