| Project/Area Number |
15590347
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | KYUSHU UNIVERSITY |
|---|
Principal Investigator |
SAKUMI Kunihiko Kyushu University, Med.Inst.Bioreg., Associate Professor, 生体防御医学研究所, 助教授 (50211933)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
FURUICHI Masato Kyushu University, Radioisotope Center, Associate Professor, アイソトープ総合センター, 助教授 (70199420)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Keywords | 8-oxoguanine / MTH1 gene / OGG1 gene / spontaneous tumorigenesis / lung |
|---|
| Research Abstract |
Using Mth1 and Ogg1 knockout mice, we evaluated the roles of these enzymes to prevent tumorigenesis and the accumulation of 8-oxoguanine(8-oxoG) in DNA. We found that lung adenoma/carcinoma spontaneously developed in Ogg1 knockout mice 1.5 years after birth in which 8-oxoG was found to accumulate in their genomes. The mean number of tumors/mouse was 0.71 for the Ogg1 knockout mice, which was five times higher than that observed in wild-type mice (0.14). Although the accumulation of 8-oxoG was also confirmed in the Ogg1,Mth1 double knockout mice, we found no tumor in the lungs of these mice. This observation suggests that Mth1 gene disruption resulted in a suppression of the tumorigenesis caused by an Ogg1 deficiency.
We found an 8-oxoguanine accumulation-dependent expression pattern of specific genes using oligoDNA microarray analysis. Because 8-oxoguanine is localized at distinct regions on the chromosomes, 8-oxoguanine may affect directly on the gene expressions.
|
