| Project/Area Number |
17590337
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
KITAGAWA Masanobu Tokyo Medical and Dental University, Graduate school, Department of Comprehensive Pathology, Professor (10177834)
|
|---|
| Project Period (FY) |
2005 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
|---|
| Keywords | retrovirus / DNA damage / apoptosis / p53 / DNA-PK / DNA-PK |
|---|
| Research Abstract |
We established the in vivo experimental system using C3H mice indicating that retroviral infection remarkably enhanced the radiation-induced apoptosis. FLU infected C3H mice exhibited lethal anemia after low dose total body irradiation (3 Gy) caused by apoptosis of hematopoietic cells of the bone marrow. The enhancement of apoptosis was p53-dependent and regulated by P13-kinases, DNA-dependent protein kinase (DNA-PK) and ataxia telangiectasia mutation kinase (ATM). In general, ATM kinase plays a role in the activation of p53 after DNA damage like irradiation. However, in this study, we could clarify that the DNA-PK bound with the FLU derived gp70 and introduced marked activation (phosphorylation) of p53. For this activation of DNA-PK, a host gene product seemed essential in association with gp70.
Using in vitro cell line systems, we confirmed the enhancement of radiation-induced apoptosis by transduction of gp70 gene derived from FLU Acute myelogenous leukemia cell lines established from radiation-induced leukemia cells of C3H mice were used for the study. Further we clarified that the enhancement of radiation-induced apoptosis was suppressed by the knock-down experiment of DNA-PK expression by RNAi.
This model would be useful for establishing the therapeutic system by the specific induction of apoptosis to abnormal cells such as cancers by using gp70 and low dose irradiation.
|
