Stoner Gary D, Dombkowski Alan A, Reen Rashmeet K, Cukovic Daniela, Salagrama Sridevi, Wang Li-Shu, Lechner John F
Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University College of Medicine, Columbus, Ohio 43240, USA.
Cancer Res. 2008 Aug 1;68(15):6460-7. doi: 10.1158/0008-5472.CAN-08-0146.
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.
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。