報告書番号

L05009

タイトル（和文）

低線量率放射線照射下での細胞増殖におけるDNA損傷修復遺伝子の役割

タイトル（英文）

Roles of DNA Repair Genes in Sustaining Cell Proliferation under Low Dose-Rate Irradiation

概要 （図表や脚注は「報告書全文」に掲載しております）

放射線生物効果の多くは、DNA2本鎖切断(DSB)に起因する。低線量率長期照射が細胞増殖率に及ぼす影響を、ニワトリBリンパ細胞株DT40を用いて作成された各種DSB修復遺伝子のノックアウト細胞を用いて検討した。その結果、1.1 mGy/hrの低線量率γ線長期照射および0.9 Gy/minの高線量率X線2 Gy照射により、非相同末端結合によるDSB修復に関与するKu70、DNA-PKcsの欠損細胞では顕著な増殖抑制効果が認められるが、相同組換え修復に関与するRad54の欠損細胞は高線量率照射後にのみ顕著な抑制効果を示した。さらに、Rad54とKu70の2重欠損細胞での増殖抑制効果は、低線量率照射ではRad54欠損細胞とかわらないが、高線量照射では最も高い効果を示した。以上により、低線量率放射線によるDSBに対する修復機構の応答は、高線量率照射の場合とは大きく異なることが示唆された。

概要 （英文）

Radiation-induced DNA double-strand break (DSB) initiates various kinds of biological effects. There is accumulating evidence indicating that the biological effects of low dose and low dose-rate radiation are different from those of high dose and high dose-rate radiation. To elucidate the molecular mechanisms, it is essential to clarify the role of DSB repair-related genes in the repair of low dose and low dose-rate radiation-induced DSBs. Here, we show that the cell growth rate of non-homologous end-joining-related Ku70 and DNA-PKcs knockout chicken DT40 cells irradiated with g-rays at 1.1 mGy/hr were significantly lower than that of homologous recombination-related Rad54 and NBS1 knockout cells and Rad54/Ku70 double-knockout cells, as well as wild-type cells. On the other hand, the growth of Rad54-/-- cells irradiated with 2 Gy of X-rays at 0.91 Gy/min was arrested as well as Ku70-/- and DNA-PKcs-/-/- cells. In addition, Rad54-/-Ku70-/- cells showed the strongest growth delay in all of knockout cells. However, NBS1-/-/- cells did not show the significant growth delay. These findings provide that the role of DSB repair-related genes in the repair of low dose-rate radiation-induced DSBs is noticeably different from that of high dose-rate. The growth delay observed in the mutants Ku70-/- and DNA-PKcs-/-/- cells irradiated with low dose-rate radiation, suggesting that these non-homologous end-joining-related genes may be utilized for the molecular marker to predict the sensitivity to low dose and low dose-rate radiation.

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