| Co-Investigator(Kenkyū-buntansha) |
KOBUNE Masayoshi SAPPORO MEDICAL UNIVERSITY, SCHOOL OF MEDICINE, INSTRUCTOR, 医学部, 助手 (90336389)
MIYANISHI Koji SAPPORO MEDICAL UNIVERSITY, SCHOOL OF MEDICINE, INSTRUCTOR, 医学部, 助手 (60372819)
|
|---|
| Budget Amount *help |
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2006: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2005: ¥10,000,000 (Direct Cost: ¥10,000,000)
|
|---|
| Research Abstract |
Recent studies have shown that excess hepatic iron accumulation in chronic hepatitis C (CHC) patients is attributable to liver injury. It is believed that free iron in the liver facilitates the formation of reactive oxygen species (ROS), including -hydroxyl radicals (.0H), which cause oxidative damage of numerous cellular components, including lipids, proteins and nucleic acids, and also cause an up-regulation of collagen synthesis. Furthermore, -OH radical is known to generate promutagenic bases such as 8-hydroxy-2'- deoxyguanosine (8-OH-dG), which has been implicated in spontaneous DNA mutagenesis and carcinogenesis. However, the mechanism of hepatocarcinogenesis due to HCV infection remains unclear, In the present study, we performed comprehensive gene analysis for target genes which are involved in oxidative DNA damage in the liver of CHC patients. Using liver biopsy specimens, high molecular DNA was extract and digested by XbaI restriction enzyme. Those DNA fragments were reacted with anti-8-OH-dG antibody followed by immunoprecipitation. Then they were washed, eluted and amplified by PCR. Thereafter, obtained DNA fragments were analyzed by 50K microarray system. As a result, we could identify 106 genes, including genes encoding transcription factors and adhesion molecules. Further, we searched SNP for DNA repair enzymes such as hOGG1 and Mutyh genes in patients with CHC and HCV-related hepatocarcinoma and found that a SNP for Mutyh would be a good marker for hepatocarcinogenesis
|
