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Environ Health Perspect. 2012 Aug;120(8):1130-6. doi: 10.1289/ehp.1104294. Epub 2012 Apr 26.

Integrated molecular analysis indicates undetectable change in DNA damage in mice after continuous irradiation at ~ 400-fold natural background radiation.

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  • 1Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

Abstract

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.

PMID:
22538203
[PubMed - indexed for MEDLINE]
PMCID:
PMC3440074
Free PMC Article
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