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Repair of DNA damage induced by accelerated heavy ions in mammalian cells proficient and deficient in the Non-homologous End-joining pathway
https://repo.qst.go.jp/records/44605
https://repo.qst.go.jp/records/44605d1283b6b-23c9-43bb-819c-8df9f116b8df
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2006-09-12 | |||||
タイトル | ||||||
タイトル | Repair of DNA damage induced by accelerated heavy ions in mammalian cells proficient and deficient in the Non-homologous End-joining pathway | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Okayasu, Ryuichi
× Okayasu, Ryuichi× Okada, Maki× Okabe, Atsushi× Noguchi, Miho× Takakura, Kaoru× Takahashi, Sentaro× 岡安 隆一× 岡田 真希× 岡部 篤史× 野口 実穂× 高倉 かほる× 高橋 千太郎 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Human and rodent cells proficient and deficient in non-homologous end joining (NHEJ) were irradiated with X rays, 70 keV/mum carbon ions, and 200 keV/mum iron ions, and the biological effects on these cells were compared. For wild-type CHO and normal human fibroblast (HFL III) cells, exposure to iron ions yielded the lowest cell survival, followed by carbon ions and then X rays. NHEJ-deficient xrs6 (a Ku80 mutant of CHO) and 180BR human fibroblast (DNA ligase IV mutant) cells showed similar cell survival for X and carbon-ion irradiation (RBE = approximately 1.0). This phenotype is likely to result from a defective NHEJ protein because xrs6-hamKu80 cells (xrs6 cells corrected with the wild-type KU80 gene) exhibited the wild-type response. At doses higher than 1 Gy, NHEJ-defective cells showed a lower level of survival with iron ions than with carbon ions or X rays, possibly due to inactivation of a radioresistant subpopulation. The G(1) premature chromosome condensation (PCC) assay with HFL III cells revealed LET-dependent impairment of repair of chromosome breaks. Additionally, iron-ion radiation induced non-repairable chromosome breaks not observed with carbon ions or X rays. PCC studies with 180BR cells indicated that the repair kinetics after exposure to carbon and iron ions behaved similarly for the first 6 h, but after 24 h the curve for carbon ions approached that for X rays, while the curve for iron ions remained high. These chromosome data reflect the existence of a slow NHEJ repair phase and severe biological damage induced by iron ions. The auto-phosphorylation of DNA-dependent protein kinase catalytic subunits (DNA-PKcs), an essential NHEJ step, was delayed significantly by high-LET carbon- and iron-ion radiation compared to X rays. This delay was further emphasized in NHEJ-defective 180BR cells. Our results indicate that high-LET radiation induces complex DNA damage that is not easily repaired or is not repaired by NHEJ even at low radiation doses such as 2 Gy. | |||||
書誌情報 |
Radiation Research 巻 165, 号 1, p. 59-67, 発行日 2006-01 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0033-7587 |