4.2 Article

The IRI-DICE hypothesis: ionizing radiation-induced DSBs may have a functional role for non-deterministic responses at low doses

期刊

RADIATION AND ENVIRONMENTAL BIOPHYSICS
卷 59, 期 3, 页码 349-355

出版社

SPRINGER
DOI: 10.1007/s00411-020-00854-x

关键词

Low-dose response; DNA double-strand break; Cis effects; Transcription; Target theory

资金

  1. University of Gothenburg
  2. Swedish Research Council [21073]
  3. Swedish Cancer Society [3427]
  4. BioCARE-a National Strategic Research Program at the University of Gothenburg
  5. Swedish Radiation Safety Authority
  6. Swedish government [725031]
  7. county councils (the ALF-agreement) [ALFGBG-725031]
  8. King Gustav V Jubilee Clinic Cancer Research Foundation
  9. Sahlgrenska University Hospital Research Funds
  10. Assar Gabrielsson Cancer Research Foundation

向作者/读者索取更多资源

Low-dose ionizing radiation (IR) responses remain an unresolved issue in radiation biology and risk assessment. Accurate knowledge of low-dose responses is important for estimation of normal tissue risk in cancer radiotherapy or health risks from occupational or hazard exposure. Cellular responses to low-dose IR appear diverse and stochastic in nature and to date no model has been proposed to explain the underlying mechanisms. Here, we propose a hypothesis on IR-induced double-strand break (DSB)-induced cis effects (IRI-DICE) and introduce DNA sequence functionality as a submicron-scale target site with functional outcome on gene expression: DSB induction in a certain genetic target site such as promotor, regulatory element, or gene core would lead to changes in transcript expression, which may range from suppression to overexpression depending on which functional element was damaged. The DNA damage recognition and repair machinery depicts threshold behavior requiring a certain number of DSBs for induction. Stochastically distributed persistent disruption of gene expression may explain-in part-the diverse nature of low-dose responses until the repair machinery is initiated at increased absorbed dose. Radiation quality and complexity of DSB lesions are also discussed. Currently, there are no technologies available to irradiate specific genetic sites to test the IRI-DICE hypothesis directly. However, supportive evidence may be achieved by developing a computational model that combines radiation transport codes with a genomic DNA model that includes sequence functionality and transcription to simulate expression changes in an irradiated cell population. To the best of our knowledge, IRI-DICE is the first hypothesis that includes sequence functionality of different genetic elements in the radiation response and provides a model for the diversity of radiation responses in the (very) low dose regimen.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.2
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据