Effects of a Black Raspberry Diet on Gene Expression in the Rat Esophagus

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.

ACKNOWLEDGMENTS

The authors acknowledge the excellent technical assistance of Ronald Nines. These studies were supported by National Institute of Health Grants RO1 CA103180 and R01CA96130 (G. D. Stoner). The microarray and bioinformatics work was facilitated by the Microarray and Bioinformatics Facility Core of the Environmental Health Sciences Center at Wayne State University (National Institute of Environmental Health Sciences Center Grant P30 ES06639).

Notes

^a Abbreviation is as follows: BRB, black raspberry.