Integrated molecular analysis indicates undetectable change in DNA damage in mice after continuous irradiation at ~ 400-fold natural background radiation.
Integrated molecular analysis indicates undetectable change in DNA damage in mice after continuous irradiation at ~ 400-fold natural background radiation.
复制标题
DOI：
10.1289/ehp.1104294
复制
发表时间：
2012-08
影响因子：
10.4
通讯作者：
Engelward BP
中科院分区：
文献类型：
--
作者：
Olipitz W;Wiktor-Brown D;Shuga J;Pang B;McFaline J;Lonkar P;Thomas A;Mutamba JT;Greenberger JS;Samson LD;Dedon PC;Yanch JC;Engelward BP
背景：在发生核事故时，人们会暴露在高水平的持续低剂量率辐射下。尽管如此，大多数文献描述了急性辐射的生物效应。目的：DNA 损伤和突变的致癌作用已得到证实。我们评估了暴露于低剂量率辐射的小鼠中 DNA 损伤和 DNA 损伤反应的几个关键标志物，以揭示与低剂量率辐射相关的潜在遗传毒性效应。方法：我们使用可变低剂量率辐照器研究低剂量率辐射，该辐照器由充满 125 碘缓冲液的泛光模型组成。小鼠连续暴露于 0.0002 cGy/min（约 400 倍背景辐射）超过 5 周。我们评估了几个辐射敏感基因的基础损伤、微核、同源重组（HR；使用荧光黄直接重复小鼠）和转录水平。结果：在低剂量率条件下，我们没有观察到 DNA 核碱基损伤产物次黄嘌呤、8-氧代-7,8-二氢鸟嘌呤、1,N6-亚乙烯基腺嘌呤或 3,N4-亚乙烯基胞嘧啶水平高于背景水平的任何变化。微核测定显示没有证据表明低剂量率辐射会引起 DNA 断裂，也没有证据表明双链断裂会引起 HR。此外，低剂量率辐射不会诱导 Cdkn1a、Gadd45a、Mdm2、Atm 或 Dbd2。重要的是，相同的总剂量在急性给药时会诱导微核和转录反应。结论：这些结果在体内动物模型中证明，降低剂量率可以抑制辐射的潜在有害影响，并提醒人们需要更深入地了解低剂量率辐射的生物学影响。
Background: In the event of a nuclear accident, people are exposed to elevated levels of continuous low dose-rate radiation. Nevertheless, most of the literature describes the biological effects of acute radiation. Objectives: DNA damage and mutations are well established for their carcinogenic effects. We assessed several key markers of DNA damage and DNA damage responses in mice exposed to low dose-rate radiation to reveal potential genotoxic effects associated with low dose-rate radiation. Methods: We studied low dose-rate radiation using a variable low dose-rate irradiator consisting of flood phantoms filled with 125Iodine-containing buffer. Mice were exposed to 0.0002 cGy/min (~ 400-fold background radiation) continuously over 5 weeks. We assessed base lesions, micronuclei, homologous recombination (HR; using fluorescent yellow direct repeat mice), and transcript levels for several radiation-sensitive genes. Results: We did not observe any changes in the levels of the DNA nucleobase damage products hypoxanthine, 8-oxo-7,8-dihydroguanine, 1,N6-ethenoadenine, or 3,N4-ethenocytosine above background levels under low dose-rate conditions. The micronucleus assay revealed no evidence that low dose-rate radiation induced DNA fragmentation, and there was no evidence of double strand break–induced HR. Furthermore, low dose-rate radiation did not induce Cdkn1a, Gadd45a, Mdm2, Atm, or Dbd2. Importantly, the same total dose, when delivered acutely, induced micronuclei and transcriptional responses. Conclusions: These results demonstrate in an in vivo animal model that lowering the dose-rate suppresses the potentially deleterious impact of radiation and calls attention to the need for a deeper understanding of the biological impact of low dose-rate radiation.
登录
查看更多内容
DOI：
10.1073/pnas.1232231100
发表时间：
2003-05-27
影响因子：
11.1
作者：
Hendricks, CA;Almeida, KH;Engelward, BP
通讯作者：
Engelward, BP
影响因子：
2.6
作者：
GOODHEAD, DT
通讯作者：
GOODHEAD, DT
DOI：
10.1073/pnas.1016045108
发表时间：
2011-05-17
影响因子：
11.1
作者：
Asaithamby, Aroumougame;Hu, Burong;Chen, David J.
通讯作者：
Chen, David J.
影响因子：
3.4
作者：
Cromheecke, M;Piers, BA;Hoekstra, HJ
通讯作者：
Hoekstra, HJ
影响因子：
4.1
作者：
Frelon, S;Douki, T;Cadet, J
通讯作者：
Cadet, J