Lechner John F, Reen Rashmeet K, Dombkowski Alan A, Cukovic Daniela, Salagrama Sridevi, Wang Li-Shu, Stoner Gary D
Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
Nutr Cancer. 2008;60 Suppl 1:61-9. doi: 10.1080/01635580802393118.
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.
一种含有5%冻干黑树莓(BRB)的饮食能显著抑制用致癌物N-亚硝基甲基苄胺(NMBA)处理的大鼠的食管癌。我们之前鉴定了在用NMBA短期处理大鼠后失调的食管基因,并确定了如果在NMBA处理之前及期间给动物喂食5%的BRB,哪些基因能维持在接近正常的表达水平。在本研究中,我们报告了BRB饮食对未处理(对照)动物食管中基因表达的影响。在5% BRB饮食喂养3周后,切除对照食管,去除黏膜下层和肌层,并进行组织学和微阵列分析。RNA微阵列显示BRB改变了36个基因的表达水平;24个基因上调,12个基因下调。上调的基因中包括与细胞基质、信号级联、转录调控、细胞凋亡、代谢相关的基因,有趣的是,还有与收缩相关的基因。大多数下调的转录本参与细胞调控、信号转导和代谢。组织病理学分析显示BRB对食管形态几乎没有影响。总之,组织学和分子研究表明,5%的BRB饮食对食管(大鼠中NMBA致癌作用的靶组织)仅产生适度影响。