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大鼠食管中被致癌物改变的基因,通过黑树莓和异硫氰酸苯乙酯均被正向调节至正常表达水平。

Carcinogen-altered genes in rat esophagus positively modulated to normal levels of expression by both black raspberries and phenylethyl isothiocyanate.

作者信息

Stoner Gary D, Dombkowski Alan A, Reen Rashmeet K, Cukovic Daniela, Salagrama Sridevi, Wang Li-Shu, Lechner John F

机构信息

Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University College of Medicine, Columbus, Ohio 43240, USA.

出版信息

Cancer Res. 2008 Aug 1;68(15):6460-7. doi: 10.1158/0008-5472.CAN-08-0146.

Abstract

Our recent study identified 2,261 dysregulated genes in the esophagi of rats that received a 1-week exposure to the carcinogen N-nitrosomethylbenzylamine (NMBA). We further reported that 1,323 of these genes were positively modulated to near-normal levels of expression in NMBA-treated animals that consumed dietary phenylethyl isothiocyanate (PEITC), a constituent of cruciferous vegetables. Herein, we report our results with companion animals that were fed a diet containing 5% freeze-dried black raspberries (BRB) instead of PEITC. We found that 462 of the 2,261 NMBA-dysregulated genes in rat esophagus were restored to near-normal levels of expression by BRB. Further, we have identified 53 NMBA-dysregulated genes that are positively modulated by both PEITC and BRB. These 53 common genes include genes involved in phase I and II metabolism, oxidative damage, and oncogenes and tumor suppressor genes that regulate apoptosis, cell cycling, and angiogenesis. Because both PEITC and BRB maintain near-normal levels of expression of these 53 genes, their dysregulation during the early phase of NMBA-induced esophageal cancer may be especially important in the genesis of the disease.

摘要

我们最近的研究在接受致癌物N-亚硝基甲基苄胺(NMBA)1周暴露的大鼠食管中鉴定出2261个失调基因。我们进一步报道,在食用十字花科蔬菜成分苯乙基异硫氰酸酯(PEITC)的NMBA处理动物中,这些基因中有1323个被正向调节至接近正常表达水平。在此,我们报告用含5%冻干黑树莓(BRB)而非PEITC的饮食喂养的对照动物的结果。我们发现,大鼠食管中2261个NMBA失调基因中有462个通过BRB恢复到接近正常表达水平。此外,我们鉴定出53个NMBA失调基因,它们同时受到PEITC和BRB的正向调节。这53个共同基因包括参与I期和II期代谢、氧化损伤的基因,以及调节细胞凋亡、细胞周期和血管生成的癌基因和肿瘤抑制基因。由于PEITC和BRB都维持这53个基因的接近正常表达水平,它们在NMBA诱导的食管癌早期阶段的失调可能在该疾病的发生中尤为重要。

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