Abstract A131: Molecular events associated with the anti-tumor effects of black raspberries in N-nitrosomethylbenzylamine-induced rat esophageal carcinogenesis

Abstract

Abstract A131 We reported that the feeding of a diet containing 5 or 10% freeze-dried black raspberries (BRB) to N-nitrosomethylbenzylamine (NMBA)-treated rats results in a 39-64% reduction in the number of esophageal papillomas when using either anti-initiation or anti-promotion/progression protocols. The molecular events associated with the effects of BRB on NMBA-induced preneoplastic and papillomatous esophageal lesions however, have not been fully elucidated. In the present study, 4-5 week-old male F344 rats were injected s.c. with NMBA (0.3 mg/kg b.w., 3x/wk for 5 wks) after which they were fed either control diet or diet containing 5% BRB until the end of the study (35 wks). Control rats were injected s.c. with a solution of DMSO/water (20:80), the vehicle for NMBA. Esophagi from vehicle control, NMBA- and NMBA + BRB-treated rats were collected at 35 weeks for histologic grading, and for microarray and Real-Time PCR analyses. Treatment with 5% BRB reduced the number of preneoplastic lesions (dysplasias) and the number and size of papillomas in the esophagus of NMBA-treated rats. When compared to esophagi from vehicle control rats, NMBA treatment alone led to the differential expression of 4,807 genes in preneoplastic esophagus and 17,846 genes in esophageal papillomas. Treatment with 5% BRB resulted in a modulation towards control levels of expression of 626 genes in preneoplastic esophagus and 627 genes in papillomas. In both preneoplastic esophagus and in papillomas, the berry-modulated genes were associated with regulation of cell proliferation, inflammation and receptor-mediated pathways. Twenty-five genes were commonly modulated (down- or up-regulated) by BRB in both preneoplastic lesions and in papillomas. Interestingly, several of these genes are associated with matrix metalloproteinases involved in tissue invasion and metastasis, cell-cell adhesion and with calcium signaling. This is the first report suggesting that berries might influence genes involved in tissue invasion and metastasis in the rat esophagus. (Supported by NCI grant No. CA103180) Citation Information: Cancer Prev Res 2008;1(7 Suppl):A131.