| Project/Area Number |
20390319
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Radiation science
|
|---|
| Research Institution | Hokkaido University |
|---|
Principal Investigator |
NISHIOKA Takeshi Hokkaido University, 大学院・保健科学研究院, 教授 (80271659)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YASUDA Motoaki 北海道大学, 大学院・歯学研究科, 准教授 (90239765)
HAGA Hisahi 北海道大学, 大学院・理学研究院, 准教授 (00292045)
TUTSMI Kaori 北海道大学, 大学院・保健科学研究院 (80344505)
SAKAI Masaharu 北海道大学, 大学院・保健科学研究院 (50162269)
HOMMA Akiniro 北海道大学, 大学院・医学研究科 (30312359)
|
|---|
| Project Period (FY) |
2008 – 2010
|
| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2010: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2008: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000)
|
|---|
| Keywords | 放射線生物学 / irradiation / p16 / repopulation / mitosis / MMP / HIF1-alpha / radiation / cancer stem cell / cell movement / Radiotherapy / TGFB-1 / 細胞形態 / 細胞運動 |
|---|
| Research Abstract |
Treatment with any cytotoxic agent can trigger surviving cells in a tumor to divide faster than before. This phenomenon is widely recognized as "repopulation". To better clarify the mechanism, gene expression profiling and pathological experiments were performed. A mouse fibrosarcoma cell line, QRsP, was used. Cells were irradiated with 10 Gy. Colony assay and cloning were performed. Six clones were established. cDNA analysis was performed on the clone that showed the largest number of colonies on the 2nd 10 Gy irradiation. Mouse transplantation experiment was then carried out. cDNA analysis showed that cyclin-dependent kinase inhibitors, p16 and p57 were down-regulated ; 14.8- and 12.0-fold, respectively for the tolerant clone. Matrix metalloproteinase 3 and 13 were up-regulated ; 22.5- and 25.8-fold, respectively. Transplantation ratio was 100% (5/5) for the tolerant clone whereas it was 40% (2/5) for the parent. Under light microscope, the mean mitotic cell number was 4.0+/-3.9 for the parent, and 12.8+/-3.4 for the tolerant clone (p<0.01, Student's t-test). This study implies that repopulation is not a temporary reaction to irradiation. It is caused probably by "clonal" gene-expression changes, though it remains unknown whether the changes are attributable to tolerant cell selection or to gene mutation/modification.
|
