Adaptive radiation‐induced epigenetic alterations mitigated by antioxidants

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.

Radiation-hormesis phenotypes, the related mechanisms and implications for disease prevention and therapy

“…The hierarchical ANP system is at least in part epiregulated, e.g., via microRNAs (miRNAs) and other means (Vaiserman 2011;Bernal et al 2013). Emerging data suggest that mild stress (e.g., low-level radiation) can rapidly alter the biogenesis of miRNAs, the expression of mRNA, and the activities of miRNA-protein complexes (Leung and Sharp 2010).…”

“…Life lasting beneficial epiregulated hormetic phenotypes (less obesity, fewer cancers, fewer diabetics) brought on by exposure to low radiation doses during gestation were demonstrated by Bernal et al (2013) for offspring using the very sensitive viable yellow agouti (A vy ) mouse model. Male offspring benefited more than did female.…”

“…Low-dose-radiation exposure during gestation causes lasting protective epigenetic changes in male offspring To determine if deleterious or protective epigenetic changes occur when exposed to low-dose radiation doses during gestation, Bernal et al (2013) utilized the viable yellow agouti (A vy ) mouse model (Duhl et al 1994). This mouse strain is very sensitive to environmental agents that alter the fetal epigenome.…”

Longitudinal epigenetic drift in mice perinatally exposed to lead

“…The metastable epiallele, CDK5-activator binding protein (Cabp IAP ) has been widely used as a biomarker of environmental exposure alteration to the epigenome. [27][28][29][30] Until now, the longitudinal changes in Cabp IAP DNA methylation level had not been described. The Cabp IAP locus has a high baseline level of methylation, explaining the small average increase across exposure groups (1.27%).…”

Comparison of blueberry ( Vaccinium spp. ) and vitamin C via antioxidative and epigenetic effects in human

“…For example, maternal dietary antioxidant supplementation mitigated DNA methylation changes in the irradiated offspring. 4 Antioxidative capacity, which leads to prevent genetic alterations by ROS, is a well-known characteristic of chemopreventive agents from natural resources for protection against oxidative stress-related diseases. 5 Blueberry (Vaccinium spp.…”