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

Effects of a Black Raspberry Diet on Gene Expression in the Rat Esophagus
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DOI:
10.1080/01635580802393118
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发表时间:
2008-01-01
影响因子:
2.9
通讯作者:
Stoner, Gary D.
Stoner, Gary D.
中科院分区:
医学4区
文献类型:
--
作者:
Lechner, John F.;Reen, Rashmeet K.;Stoner, Gary D.

文献摘要

被引文献

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含有5%冻干黑树莓(BRB)的饮食显著抑制了用致癌物N-亚硝基甲基苄胺(NMBA)处理的大鼠的食管癌。我们以前确定了食管基因,变得失调后,短期治疗的大鼠与NMBA和确定哪些基因保持在接近正常水平的表达,如果动物喂养5%的BRB之前和期间NMBA治疗。在这项研究中,我们报告了BRB饮食对未经处理(对照)动物食管中基因表达的影响。在5%BRB饮食3周后,切除对照食管,剥离粘膜下层和肌层,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个上调,12个下调。上调的基因包括与细胞基质、信号级联、转录调节、凋亡、代谢和有趣的收缩相关的基因。大多数下调的转录物参与细胞调节、信号转导和代谢。组织学分析表明,BRB对食管形态学影响很小或没有影响。总之,组织学和分子研究表明,5% BRB饮食对食道(大鼠NMBA致癌的靶组织)仅产生适度影响。
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.