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Integrated Molecular Analysis Indicates Undetectable Change in DNA Damage in Mice after Continuous Irradiation at ~ 400-fold Natural Background Radiation

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dc.contributor.author Olipitz, Werner
dc.contributor.author Shuga, Joe
dc.contributor.author Pang, Bo
dc.contributor.author Mcfaline, Jose L.
dc.contributor.author Lonkar, Pallavi
dc.contributor.author Thomas, Aline
dc.contributor.author Mutamba, James T.
dc.contributor.author Greenberger, Joel S.
dc.contributor.author Samson, Leona D.
dc.contributor.author Dedon, Peter C.
dc.contributor.author Yanch, Jacquelyn C.
dc.contributor.author Engelward, Bevin P.
dc.contributor.author Wiktor-Brown, Dominika
dc.date.accessioned 2012-11-16T20:45:25Z
dc.date.available 2012-11-16T20:45:25Z
dc.date.issued 2012-04
dc.identifier.issn 0091-6765
dc.identifier.issn 1552-9924
dc.identifier.uri http://hdl.handle.net/1721.1/74671
dc.description.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. en_US
dc.description.sponsorship United States. Dept. of Energy (DE-FG02-05ER64053) en_US
dc.description.sponsorship United States. Dept. of Energy (R33-CA112151) en_US
dc.description.sponsorship United States. Dept. of Energy (1U19AI68021-06) en_US
dc.description.sponsorship National Institutes of Health (U.S.) (NIH ES02109) en_US
dc.description.sponsorship National Institutes of Health (U.S.) (grant P01-CA026731) en_US
dc.description.sponsorship Austrian Academy of Sciences en_US
dc.description.sponsorship National Institute of General Medical Sciences (U.S.) (Interdepartmental Biotechnology Training Program (GM008334)) en_US
dc.language.iso en_US
dc.publisher National Center for Biotechnology Information en_US
dc.relation.isversionof http://dx.doi.org/10.1289/ehp.1104294 en_US
dc.rights Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. en_US
dc.source PMC en_US
dc.title Integrated Molecular Analysis Indicates Undetectable Change in DNA Damage in Mice after Continuous Irradiation at ~ 400-fold Natural Background Radiation en_US
dc.type Article en_US
dc.identifier.citation Olipitz, Werner et al. “Integrated Molecular Analysis Indicates Undetectable Change in DNA Damage in Mice After Continuous Irradiation at ~ 400-fold Natural Background Radiation.” Environmental Health Perspectives 120.8 (2012): 1130–1136. Web. en_US
dc.contributor.department Massachusetts Institute of Technology. Department of Biological Engineering en_US
dc.contributor.department Massachusetts Institute of Technology. Department of Nuclear Science and Engineering en_US
dc.contributor.department Massachusetts Institute of Technology. Department of Biology en_US
dc.contributor.department Massachusetts Institute of Technology. Center for Environmental Health Sciences en_US
dc.contributor.mitauthor Olipitz, Werner
dc.contributor.mitauthor Wiktor-Brown, Dominika
dc.contributor.mitauthor Shuga, Joe
dc.contributor.mitauthor Pang, Bo
dc.contributor.mitauthor Mcfaline, Jose L.
dc.contributor.mitauthor Lonkar, Pallavi
dc.contributor.mitauthor Thomas, Aline
dc.contributor.mitauthor Mutamba, James T.
dc.contributor.mitauthor Samson, Leona D.
dc.contributor.mitauthor Dedon, Peter C.
dc.contributor.mitauthor Yanch, Jacquelyn C.
dc.contributor.mitauthor Engelward, Bevin P.
dc.relation.journal Environmental Health Perspectives en_US
dc.identifier.mitlicense PUBLISHER_POLICY en_US
dc.eprint.version Final published version en_US
dc.type.uri http://purl.org/eprint/type/JournalArticle en_US
eprint.status http://purl.org/eprint/status/PeerReviewed en_US
dspace.orderedauthors Olipitz, Werner; Wiktor-Brown, Dominika; Shuga, Joe; Pang, Bo; Mcfaline, Jose L.; Lonkar, Pallavi; Thomas, Aline; Mutamba, James T.; Greenberger, Joel S.; Samson, Leona D.; Dedon, Peter C.; Yanch, Jacquelyn C.; Engelward, Bevin P. en_US


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