2005 Fiscal Year Final Research Report Summary
Molecular mechanisms of the response to low-dose radiation in hTERT-immortalized human cells
Project/Area Number |
14380260
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
環境影響評価(含放射線生物学)
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Research Institution | Aichi Cancer Center |
Principal Investigator |
ISHIZAKI Kanji Aichi Cancer Center, Radiation Biol., Head of Lab., 中央実験部, 部長 (70111987)
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Co-Investigator(Kenkyū-buntansha) |
KUMIMOTO Hiroshi Aichi Cancer Center, Radiation Biology, Researcher, 中央実験部, 研究員 (00291170)
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Project Period (FY) |
2002 – 2005
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Keywords | hTERT gene / human cells / low-dose, low-dose-rate radiation / DNA repair / ATM protein / damage response |
Research Abstract |
In this study, we used human cells immortalized by introduction of the hTERT gene to reveal the effects of low-dose and low-dose-rate radiation on cells in human bodies. Cells derived from normal individuals were very resistant to low-dose-rate radiation since DNA damage induced by low-dose-rate radiation was efficiently repaired in these cells. During irradiation at low-dose-rate, ATM protein was partly activated but downstream p53 protein was barely activated. On the contrary, AT cells defective in ATM protein were sensitive to low-dose-rate radiation as like as to high-dose-rate radiation. We also found that some part of DNA damage induce by low-dose-rate irradiation in AT cells were not repaired for long time. These results suggest that ATM protein partly activated in cells irradiated with low-dose or at low-dose-rate can promote repair of DNA damage induced by these radiation but can not induce downstream checkpoint function. To search change of expression of various genes during low-dose-rate irradiation, we performed micro-array analysis using 25k cDNA arrays. Among variety of genes those showed change of expression, we interested in the histone H1 family genes. It is known that histone proteins belonging to H2 and H3 families are involved in chromatin reconstruction but in our experiments expression of the genes of these proteins were not changed during low-dose-rate irradiation. Using real-time PCR, we further analyzed expression of these histone H1 family genes and confired increased expression during low-dose-rate radiation. We are now analyzing function of histon H1 family protein in DNA damage response.
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Research Products
(10 results)