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dc.contributor.authorBernal, Autumn J.en_GB
dc.contributor.authorDolinoy, Dana C.en_GB
dc.contributor.authorHuang, Daleen_GB
dc.contributor.authorSkaar, David A.en_GB
dc.contributor.authorWeinhouse, Carenen_GB
dc.contributor.authorJirtle, Randy L.en_GB
dc.date.accessioned2013-07-16T10:15:57Z
dc.date.available2013-07-16T10:15:57Z
dc.date.issued2012
dc.identifier.citationBernal, A.J., Dolinoy, D.C., Huang, D. et al. (2012) 'Adaptive radiation-induced epigenetic alterations mitigated by antioxidants', FASEB Journal, 27(2), pp.665-671en_GB
dc.identifier.issn0892-6638
dc.identifier.issn1530-6860
dc.identifier.doi10.1096/fj.12-220350
dc.identifier.urihttp://hdl.handle.net/10547/296188
dc.description.abstractHumans 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.
dc.language.isoenen
dc.publisherFederation of American Society of Experimental Biologyen_GB
dc.relation.urlhttp://www.fasebj.org/cgi/doi/10.1096/fj.12-220350en_GB
dc.rightsArchived with thanks to The FASEB Journalen_GB
dc.subjectDNA methylationen_GB
dc.subjectagouti miceen_GB
dc.subjecthormesisen_GB
dc.subjectreactive oxygen speciesen_GB
dc.titleAdaptive radiation-induced epigenetic alterations mitigated by antioxidantsen
dc.typeArticleen
dc.identifier.journalFASEB Journalen_GB
html.description.abstractHumans 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.


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