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

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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