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    Adaptive radiation-induced epigenetic alterations mitigated by antioxidants

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    Authors
    Bernal, Autumn J.
    Dolinoy, Dana C.
    Huang, Dale
    Skaar, David A.
    Weinhouse, Caren
    Jirtle, Randy L.
    Issue Date
    2012
    Subjects
    DNA methylation
    agouti mice
    hormesis
    reactive oxygen species
    
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    Abstract
    Humans are exposed to low-dose ionizing radiation (LDIR) from a number of environmental and medical sources. In addition to inducing genetic mutations, there is concern that LDIR may also alter the epigenome. Such heritable effects early in life can either be positively adaptive or result in the enhanced formation of diseases, including cancer, diabetes, and obesity. Herein, we show that LDIR significantly increased DNA methylation at the viable yellow agouti (A(vy)) locus in a sex-specific manner (P=0.004). Average DNA methylation was significantly increased in male offspring exposed to doses between 0.7 and 7.6 cGy, with maximum effects at 1.4 and 3.0 cGy (P<0.01). Offspring coat color was concomitantly shifted toward pseudoagouti (P<0.01). Maternal dietary antioxidant supplementation mitigated both the DNA methylation changes and coat color shift in the irradiated offspring. Thus, LDIR exposure during gestation elicits epigenetic alterations that lead to positive adaptive phenotypic changes that are negated with antioxidants, indicating they are mediated in part by oxidative stress. These findings provide evidence that in the isogenic A(vy) mouse model, epigenetic alterations resulting from LDIR play a role in radiation hormesis, bringing into question the assumption that every dose of radiation is harmful.
    Citation
    Bernal, A.J., Dolinoy, D.C., Huang, D. et al. (2012) 'Adaptive radiation-induced epigenetic alterations mitigated by antioxidants', FASEB Journal, 27(2), pp.665-671
    Publisher
    Federation of American Society of Experimental Biology
    Journal
    FASEB Journal
    URI
    http://hdl.handle.net/10547/296188
    DOI
    10.1096/fj.12-220350
    Additional Links
    http://www.fasebj.org/cgi/doi/10.1096/fj.12-220350
    Type
    Article
    Language
    en
    ISSN
    0892-6638
    1530-6860
    ae974a485f413a2113503eed53cd6c53
    10.1096/fj.12-220350
    Scopus Count
    Collections
    Muscle Cellular and Molecular Physiology

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