Homologous recombination is involved in the repair response of mammalian cells to low doses of tritium
Homologous recombination is involved in the repair response of mammalian cells to low doses of tritium
复制标题
DOI：
10.1667/rr1089.1
复制
发表时间：
2008-08-01
影响因子：
3.4
通讯作者：
Lopez, Bernard S.
中科院分区：
文献类型：
--
作者：
Saintigny, Yannick;Roche, Stephane;Lopez, Bernard S.
组织中的放射性化合物可具有由亚细胞区室中的能量沉积引起的生物效应。我们讨论了[H-3]或[C-14]胸苷掺入哺乳动物DNA的遗传后果。低剂量[H-3]胸苷在CHO细胞中的灵敏度比[C-14]胸苷高。与野生型细胞相比，同源重组（HR）缺陷型细胞对低剂量的[H-3]胸苷更敏感，但对任何剂量的[C-14]胸苷都不敏感。然而，XRCC 4缺陷细胞对低剂量和高剂量的[H-3]和[C-14]胸苷都敏感，表明引入了DNA双链断裂，这通过γ-H2 AX病灶形成得到证实。虽然γ射线只在毒性剂量下诱导可测量的HR，但亚致死水平的[H-3]或[C-14]胸苷强烈诱导HR。RAD 51基因转换途径参与，因为[H-3]胸苷诱导RAD 51灶，而[3（H）]胸苷诱导的HR被显性负性RAD 51的表达废除。总之，标记核苷酸掺入（低剂量）后，涉及HR和非同源末端连接途径;遗传效应与发射的能量呈负相关，但与细胞核中沉积的能量呈正相关，表明低能R-粒子发射体在无毒剂量下可能诱导基因组不稳定。(C)2008年，辐射研究协会。
Radioactive compounds incorporated in tissues can have biological effects resulting from energy deposition in subcellular compartments. We addressed the genetic consequences of [H-3] or [C-14]thymidine incorporation into mammalian DNA. Low doses of [H-3]thymidine in CHO cells led to enhanced sensitivity compared With [C-14]thymidine. Compared with wild-type cells, homologous recombination (HR)-deficient cells were more sensitive to lower doses of [H-3]thymidine but not to any dose of [C-14]thymidine. XRCC4-defective cells, however, were sensitive to both low and high doses of [H-3] and [C-14]thymidine, suggesting introduction of DNA double-strand breaks, which were confirmed by gamma-H2AX focus formation. While gamma rays induced measurable HR only at toxic doses, sublethal levels of [H-3] or [C-14]thymidine strongly induced HR. The level of stimulation was in an inverse relationship to the emitted energies. The RAD51 gene conversion pathway was involved, because [H-3]thymidine induced RAD51 foci, and [3(H)]thymidine-induced HR was abrogated by expression of dominant negative RAD51. In conclusion, both HR and non-homologous end-joining pathways were involved after labeled nucleotide incorporation (low doses); genetic effects were negatively correlated with the energy emitted but were positively correlated with the energy deposited in the nucleus, suggesting that low-energy R-particle emitters, at non-toxic doses, may induce genomic instability. (C) 2008 by Radiation Research Society.