Oligonucleotide microarray-based genome-wide analysis of gene expression in oxidative stress-induced hepatitis and tumorigenesis

内源或外源产生的活性氧(ROS)和自由基在多种基因的表达中起着第二信使的重要作用。如果ROS的生成和消除之间的生理失衡持续下去，这种氧化应激将对各种组织、细胞和DNA造成损害，并可能引发各种疾病。在这项研究中，我们通过基于寡核苷酸微阵列的全基因组分析(使用基因芯片)来研究氧化应激是否与慢性肝炎发展为肝肿瘤有关。在人类肝脏肿瘤中，氧化应激与肝脏肿瘤发生之间的直接关系尚未得到充分证明，因为肝脏疾病的病因和患者背景非常不同。为了尽可能减少各种因素的影响，采用Long-Evans肉桂皮(Long-Evans Cinnamon，LEC)大鼠作为氧化应激相关动物模型。分析氧化应激下的链式反应样基因表达谱可能使u…S更多的是为了解决肿瘤的发生机制。LEC大鼠在1岁左右自然形成肝脏肿瘤。分别对每个肿瘤组织和非肿瘤组织进行全基因组基因表达分析。在31099个基因中，分别有68个和32个基因被选为与肿瘤发生相关的候选基因。肿瘤组织中高表达的基因包括与细胞黏附、结缔组织生长因子、血管生成、形态发生(包括血管生成)、细胞周期/细胞生长、原癌基因、代谢/信号转导有关的基因。肿瘤组织中高表达的基因包括与抗血管生成、酶和新陈代谢有关的基因，以消除和/或减少ROS，以及再生，如手稿(提交中)和网站(准备中)中详细描述的。此外，一种具有多种生理活性的糖蛋白在分析过程中已被证实是一种抗氧化剂。我们为这种物质的特殊用途申请了专利。较少

Endogenously or exogenously generated reactive oxygen species (ROS) and free radicals play an important role as second messengers in the expression of various genes. If a physiologic imbalance between the generation and elimination of ROS would continue, such oxidative stress would cause damage to various tissues, cells, and DNA, and might induce various diseases. In this study, we investigated whether oxidative stress is related to the progression of chronic hepatitis to hepatic tumor by oligonucleotide microarray-based genome-wide analysis (using Gene Chip^<TM>). In human liver tumors, the direct relationship between oxidative stress and liver tumorigenesis has not been fully demonstrated, because etiology of liver diseases and patient backgrounds are very various. To reduce various factors whatever possible, Long-Evans Cinnamon (LEC) rats were used as an oxidative stress-related animal model. Analysis of chain reaction-like gene expression profile under oxidative stress may enable u … More s to resolve the mechanism of tumorigenesis.LEC rats naturally develop hepatic tumor 〜1 year of age. Genome-wide analysis of gene expression was performed for each tumor and non-tumor tissue, respectively. Of 31099 genes, 68 and 32 genes were selected as candidates related to tumorigenesis, respectively. Highly expressed genes in tumor tissues contained those concerned with cell adhesion, connective tissue growth factor, vasculogenesis, morphogenesis (including angiogenesis), cell cycle/cell growth, pro-oncogene, metabolism/signal transduction that considered necessary for tumor growth. Highly expressed genes in tumor tissues contained those concerned with anti-angiogenesis, enzymes and metabolism to eliminate and/or reduce ROS, and regeneration, as described in detail in manuscripts (in submission) and on a Web site (in preparation). Furthermore, A glycoprotein with versatile physiologic activities has been validated as an anti-oxidant in the process of analysis. We applied for a patent on the specialized usage of the substance. Less