Imprinted genes and transpositions: epigenomic targets for low dose radiation effects. Final report

doi:10.2172/1062638

GSTDTAP > 地球科学

DOI	10.2172/1062638
报告编号	DOE--FG02-05ER64101
来源ID	OSTI ID: 1062638
	Imprinted genes and transpositions: epigenomic targets for low dose radiation effects. Final report
	Jirtle, Randy L.
	2012-10-11
出版年	2012
页数	2
语种	英语
国家	美国
领域	地球科学
英文摘要	The overall hypothesis of this grant application is that low dose ionizing radiation (LDIR) elicits adaptive responses in part by causing heritable DNA methylation changes in the epigenome. This novel postulate was tested by determining if the level of DNA methylation at the Agouti viable yellow (A{sup vy}) metastable locus is altered, in a dose-dependent manner, by low dose radiation exposure (<10 cGy) during early gestation. This information is particularly important to ascertain given the increased use of CT scans in disease diagnosis, increased number of people predicted to live and work in space, and the present concern about radiological terrorism. We showed for the first time that LDIR significantly increased DNA methylation at the A{sup 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 cGy and 7.6 cGy with maximum effects at 1.4 cGy and 3.0 cGy (p<0.01). Offspring coat color was concomitantly shifted towards pseudoagouti (p<0.01). Maternal dietary antioxidant supplementation mitigated both the DNA methylation changes and coat color shift in the irradiated offspring (p<0.05). 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 Avy 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. Our findings not only have significant implications concerning the mechanism of hormesis, but they also emphasize the potential importance of this phenomenon in determining human risk at low radiation doses. Since the epigenetic regulation of genes varies markedly between species, the effect of LDIR on other epigenetically labile genes (e.g. imprinted genes) in animals and humans needs to be defined.
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来源平台	US Department of Energy (DOE)
引用统计
文献类型	科技报告
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/5735
专题	地球科学
推荐引用方式 GB/T 7714	Jirtle, Randy L.. Imprinted genes and transpositions: epigenomic targets for low dose radiation effects. Final report,2012.