1995 Fiscal Year Final Research Report Summary
Studies on Molecular Mechanisms of Radiation Response
| Project/Area Number |
05404078
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
環境影響評価(含放射線生物学)
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SASAKI Masao Kyoto University, Radiation Biology Center, Professor, 放射線生物研究センター, 教授 (20013857)
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| Project Period (FY) |
1993 – 1995
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| Keywords | Radiation response / Low dose radiation / Adaptive response / Signal transduction / Early response gene / Gene expression / MAP kinase / Inverse dose-rate effect |
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| Research Abstract |
Mammalian cells are highly sensitive to small doses of radiations and exppress variable physiological functions. The present study was started in 1993 to clarify the molecular mechanisms of such radiation response and to provide a new biological basis of radiation effects. During the past 2 years of the study, it has been found that (1) the cultured mouse cells previously irradiated with small doses of X-rays become refractory to chromosome aberration formation, mutation induction and cell killing but more susceptible to malignant transformation by subsequent challenging doses, (2) the optimum doses for such response is below 0.1 Gy, (3) oxidative radicals may be responsible for such effect, and (4) the cells express early response genes such as jun and fos. In this year, studies were extended to clarify the cellular signal transduction pathways, and revealed that the delta-isoform of phospholipase C is responsible for the radiation respopnse where X-ray signals were transmitted to protein kinase C and p38 kinase. The signal transduction pathways are thus unique to X-ray exposures and distinct from that for UV exposure, where JNK kinase is responsible. With this signalling pathway cells show adaptive response and growth stimulatory response towards the enhancement of malignant transformation. Taken those response characteristics obtaianed in this study together, the consequences of low dose-rate protracted exposures to radiations were simulated by computer. The results suggest that with the decrease of dose-rate transformation will be enhanced resulting in the inverse dose-rate effect while the mutation will be suppressed to occur. This is consistent with the observations in the literatures and provides a new theory for the inverse dose-rate effect of in vitro malignant transformation.
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