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      Dose and Radioadaptive Response Analysis of Micronucleus Induction in Mouse Bone Marrow

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          Abstract

          Enhanced cellular DNA repair efficiency and suppression of genomic instability have been proposed as mechanisms underlying radio-adaptive responses following low-dose radiation exposures. We previously showed that low-dose γ irradiation does not generate radio-adaptation by lowering radiation-induced cytogenetic damage in mouse spleen. Since radiation may exert tissue-specific effects, we extended these results here by examining the effects of γ radiation on cytogenetic damage and proliferative index in bone marrow erythrocytes of C57BL/6 and BALB/c mice. In C57BL/6 mice, the induction of micronuclei in polychromatic erythrocytes (MN-PCE) was observed at radiation doses of 100 mGy and greater, and suppression of erythroblast maturation occurred at doses of >500 mGy. A linear dose–response relationship for MN-PCE frequencies in C57BL/6 mice was established for radiation doses between 100 mGy and 1 Gy, with departure from linearity at doses of >1 Gy. BALB/c mice exhibited increased MN-PCE frequencies above baseline following a 20 mGy radiation exposure but did not exhibit radio-sensitivity relative to C57BL/6 mice following 2 Gy exposure. Radio-adaptation of bone marrow erythrocytes was not observed in either strain of mice exposed to low-dose priming γ irradiation (single doses of 20 mGy or 100 mGy or multiple 20 mGy doses) administered at various times prior to acute 2 Gy irradiation, confirming the lack of radio-adaptive response for induction of cytogenetic damage or suppression or erythrocyte proliferation/maturation in bone marrow of these mouse strains.

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          Most cited references84

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            Non-targeted effects of ionising radiation--implications for low dose risk.

            Non-DNA targeted effects of ionising radiation, which include genomic instability, and a variety of bystander effects including abscopal effects and bystander mediated adaptive response, have raised concerns about the magnitude of low-dose radiation risk. Genomic instability, bystander effects and adaptive responses are powered by fundamental, but not clearly understood systems that maintain tissue homeostasis. Despite excellent research in this field by various groups, there are still gaps in our understanding of the likely mechanisms associated with non-DNA targeted effects, particularly with respect to systemic (human health) consequences at low and intermediate doses of ionising radiation. Other outstanding questions include links between the different non-targeted responses and the variations in response observed between individuals and cell lines, possibly a function of genetic background. Furthermore, it is still not known what the initial target and early interactions in cells are that give rise to non-targeted responses in neighbouring or descendant cells. This paper provides a commentary on the current state of the field as a result of the non-targeted effects of ionising radiation (NOTE) Integrated Project funded by the European Union. Here we critically examine the evidence for non-targeted effects, discuss apparently contradictory results and consider implications for low-dose radiation health effects. Copyright © 2012 Elsevier B.V. All rights reserved.
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              A rapid in vivo test for chromosomal damage.

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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                13 September 2016
                September 2016
                : 17
                : 9
                : 1548
                Affiliations
                Canadian Nuclear Laboratories, Radiobiology and Health, Chalk River, ON K0J1J0, Canada; rebecca.mantha@ 123456cnl.ca (R.R.M.); yvonne.devantier@ 123456cnl.ca (Y.D.); jenya.petoukhov@ 123456gmail.com (E.S.P.); bridech@ 123456ecolecatholique.ca (C.L.A.B.); mandy.serran@ 123456cnl.ca (M.L.S.); dmitry.klokov@ 123456cnl.ca (D.Y.K.)
                Author notes
                [* ]Correspondence: laura.bannister@ 123456cnl.ca ; Tel.: +1-613-584-8811 (ext. 43828); Fax: +1-613-584-8217
                Article
                ijms-17-01548
                10.3390/ijms17091548
                5037821
                27649149
                6d1f7920-41de-4b32-9cac-fd60254dc36e
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 04 August 2016
                : 05 September 2016
                Categories
                Article

                Molecular biology
                ionizing radiation,dose–response,mouse,c57bl/6,balb/c,cytogenetic damage,radio-adaptive response,bone marrow,erythrocyte,micronucleus

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