1998 Fiscal Year Final Research Report Summary
Regulatory Mechanism of Biological Response to Low-dose Radiations and Its Consequences
| Project/Area Number |
08408021
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
環境影響評価(含放射線生物学)
|
|---|
| Research Institution | KYOTO UNIVERSITY |
|---|
Principal Investigator |
SASAKI Masao Kyoto University, Radiation Biology Center, Professor, 放射線生物研究センター, 教授 (20013857)
|
|---|
| Project Period (FY) |
1996 – 1998
|
| Keywords | Low-dose radiation / Adaptive response / Signal transduction / p53 gene / DNA double strand breaks / Apoptosis / Mutation / Radiation effect |
|---|
| Research Abstract |
Eukaryotic organisms respond sensitively to low-level radiations, and become resistant to the induction of mutation and cell killing by subsequent radiations. The response called radioadaptive response is considered to be a reflection of novel life maintenance mechanism and receiving a special concern in the context of radiation effects as well as life science. This study aimed to elucidate the molecular mechanisms and biological significance of the adaptive response. In 1996-1997, we found that the radioadaptive response is mediated by a circuitry signal transduction pathway involving PKC-alpha/p38 MAPK/PLC-delta, which also played a role in the dose recognition, and that the response was p53 dependent. In this year, the studies were further expended toward the elucidation of the molecular mechanism of the acquirement of radioresistance, and following results were obtained. Radiation induces apoptosis in a p53-dependent manner, but prior irradiation with low-dose abrogate the radiation-induced apoptosis, indicating that radioadaptation blocks the death signal from DNA damage. This has been confirmed by studying the fidelity of rejoining of DNA double strand breaks in the in vitro assay system. The nuclear extract obtained from the cells irradiated with low-dose radiation promoted an error-free rejoining. These lines of evidence strongly point to a possibility that the adaptive response plays a role in the reduction of mutation and escaping from the cellular death, which might be a reflection of a driving force in evolution as well as constitute an underlying mechanism of bioregulation of the biological effects of low-level radiations.
|
