B1

Our recent report (Reen RK, et al. Cancer Res 2007;67:6484-92) described 2261 changes in gene expressions in esophagi from rats that received a short-term exposure to the carcinogen, N-Nitrosomethylbenzylamine (NMBA). We also identified 1323 genes that were differentially modulated to near-normal levels of expression by co-treatment of rats with phenylethylisothiocyanate (PEITC). Herein we report a companion study wherein the rats were fed AIN-76A diet or AIN-76A diet containing 5% freeze-dried black raspberries (BRB) for three weeks. During the third week one-half of the diet-only animals and one-half of the BRB-diet animals received three s.c. doses of NMBA (0.5 mg/kg b.w.). All animals were sacrificed 24h after the last dose of NMBA. Esophagi were rapidly excised and both processed for histological grading and extracted for RNA for microarray profiling. Histopathological analysis showed that treatment of rats with BRB had a protective effect on NMBA-induced lesions in the rat esophagus. We identified 24 genes that were up-regulated by BRB alone, and although the specimens were carefully stripped of the submucosal and muscularis layers before extracting their RNA, 10 of these are associated with muscle and/or contraction processes. Twelve genes were down-regulated by the BRB diet only, and two of these, Rbbp6 and RGD1564921_predicted, were also down-regulated by PEITC alone. We found that 259 of the 2261 genes affected by NMBA were expressed at near control levels (± 33%) in the esophagi of rats treated with both 5% BRB and NMBA. Fifty of these genes were also restored to control levels of transcription by PEITC. Overall, the results of our study indicate that BRB-treatment had a genome-wide modulating effect on NMBA-caused dysregulation of gene expression, including genes involved in phase I and phase II metabolism, oxidative damage, apoptosis, cell-cycling, and angiogenesis.
 >Supported by NCI grants CA096130 and CA103180 to GDS.

Sixth AACR International Conference on Frontiers in Cancer Prevention Research-- Dec 5-8, 2007; Philadelphia, PA