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RADIATION-INDUCED LONG LIVED RADICALS CAUSING MUTATION AND TRANSFORMATION

RADIATION-INDUCED LONG LIVED RADICALS CAUSING MUTATION AND TRANSFORMATION
辐射诱导的长寿命自由基导致突变和转化
批准号:
13480171
负责人:
WATANABE Masami
金额:
$9.6万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
2001
资助国家:
日本
项目状态:
已结题
起止时间:
2001 至 2003

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中文摘要
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英文摘要
Many researches studying in area of radiation biology have been believed that active short life-time radicals such as OH and H radicals, play an important role to express genoto do effects of radiation h cells, such as mutation and cancer induction. However, we found a new type of radicals with long life-time (T_<1/2>20hr) in gamma ray hmdiated golden hamster embryo (GHE) cells at room temperature by using ESR spectroscopy. It may be more important in mutation induction than the active short live radials. When Vitamin C (MA) is added to the gamma-or X-irradiated cells at 20 min or 6 hr after the irradiation, respectively, LLR are scavenged by them simuhaneousty with the drastic suppression of genotoxicity such as mutation and transformation. Since reactive oxygen species (ROS) disappear within microsecond after the irradiation, AsA do not scavenge the ROS but LLR. Therefore, we have proposed that LLR must be responsible radicals for inducing mutation, and probably important for the genotoxicity in the irradiated mammalian cells. Addition of AsA to the cells before or after irradiation does not have any effects on reducing cell death and chromosomal aberration. By the studies using ESEEM spectroscopy, we found that LLR probably locate in interior of biopolymers where few water molecules exist. By further analysis of the ESR spectra of LLR and comparison of the yields of radicals in proteins and DNA, we reached to the conclusion that LLR are produced in protein and assigned as sulfinyl radicals as oxidized cysteine groups. LLR are not produced in DNA or in lipids. Our result show that the LLR produced in protein is responsible for the gene mutation in irradiated cells. Although this contradicts now common view in the radiation biology, many unresolved phenomena in the radiation biology can be explained well.
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Hamada, N., Kodama, S., Suzuki, K., Watanabe, M.: "Gap junctional intercellular communication and cellular response to heat stress"Carcinogenesis. 24・11. 1723-1728 (2003)
Hamada, N.、Kodama, S.、Suzuki, K.、Watanabe, M.:“间隙连接细胞间通讯和细胞对热应激的反应”24・11(2003)。
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Matsuda, N., Horikawa, M., Yoshida, M., Watanabe.M, Nagahata, M., Teramoto, A., Abe, K: "Enhanced DNA synthesis accompanied by constitutive phaophorylation of the ERK pathway in human fibroblasts cultured on a polyeectrolyte complex."Biomaterials. 24. 477
Matsuda, N.、Horikawa, M.、Yoshida, M.、Watanabe.M、Nagahata, M.、Teramoto, A.、Abe, K:“在培养的人成纤维细胞中,DNA 合成增强,伴随 ERK 途径的组成型磷酸化。
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M.Miyakoda, K.Suzuki, S.Kodama, M.Watanabe: "Activation of ATM by heat shock and phosphorylation of p53"Oncogene. 21・7. 1090-1096 (2002)
M.Miyakoda、K.Suzuki、S.Kodama、M.Watanabe:“通过热休克和 p53 磷酸化激活 ATM”Oncogene 21・7 (2002)。
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