A Single Whole-Body Low Dose X-Irradiation Does Not Affect L1, B1 and IAP Repeat Element DNA Methylation Longitudinally

Abstract

The low dose radioadaptive response has been shown to be protective against high doses of radiation as well as aging-induced genomic instability. We hypothesised that a single whole-body exposure of low dose radiation would induce a radioadaptive response thereby reducing or abrogating aging-related changes in repeat element DNA methylation in mice. Following sham or 10 mGy X-irradiation, serial peripheral blood sampling was performed and differences in Long Interspersed Nucleic Element 1 (L1), B1 and Intracisternal-A-Particle (IAP) repeat element methylation between samples were assessed using high resolution melt analysis of PCR amplicons. By 420 days post-irradiation, neither radiation- or aging-related changes in the methylation of peripheral blood, spleen or liver L1, B1 and IAP elements were observed. Analysis of the spleen and liver tissues of cohorts of untreated aging mice showed that the 17–19 month age group exhibited higher repeat element methylation than younger or older mice, with no overall decline in methylation detected with age. This is the first temporal analysis of the effect of low dose radiation on repeat element methylation in mouse peripheral blood and the first to examine the long term effect of this dose on repeat element methylation in a radiosensitive tissue (spleen) and a tissue fundamental to the aging process (liver). Our data indicate that the methylation of murine DNA repeat elements can fluctuate with age, but unlike human studies, do not demonstrate an overall aging-related decline. Furthermore, our results indicate that a low dose of ionising radiation does not induce detectable changes to murine repeat element DNA methylation in the tissues and at the time-points examined in this study. This radiation dose is relevant to human diagnostic radiation exposures and suggests that a dose of 10 mGy X-rays, unlike high dose radiation, does not cause significant short or long term changes to repeat element or global DNA methylation.

Effects of ionizing radiation on DNA methylation: from experimental biology to clinical applications

“…Irradiation of C57BL/6 mice with 10 mGy of x-rays (100–140 kVp at 13.9 mGy/min dose-rate) did not result in any persistent alterations in the DNA methylation of LINE-1, SINE B1 (non-autonomous retrotransposon that corresponds to human Alu elements), and Intracisternal A Particle (IAP) elements in peripheral blood, spleen, and liver tissues (Newman et al, 2014a). At the same time, exposure to a dose of 1 Gy of x-rays was characterized by the strain-, tissue-, sex-, and time-dependent alterations in methylation of the abovementioned repetitive elements (Newman et al, 2014b).…”

Response of transposable elements to environmental stressors

“…Exposure to 10 mGy of X-ray (using an attenuated 140 kVp X-ray beam (8 mm Al half value layer) from a Gulmay D3150 superficial X-ray unit; dose-rate of 13.9 mGy/min) did not result in any persistent alterations in the methylation of L1, SINE B1, and IAP TEs in peripheral blood, spleen, or liver of C57BL/6 mice [98]. Exposure to a higher dose of 1 Gy of X-irradiation led to strain-, tissue-, sex-, and time-dependent alterations in methylation of the TEs [99].…”

Low-Dose Gamma Irradiation Enhances Superoxide Anion Production by Nonirradiated Cells Through TGF-β1-Dependent Bystander Signaling

“…For example, Newman et al, demonstrated that a single radiation dose in a mouse model comparable to human diagnostic radiation exposure did not result in significant long-or short-term changes to repeat elements or global DNA methylation patterns (88). Conversely, Kovalchuk et al, showed that chronic low-dose exposure proved to be a more potent inducer of epigenetic effects than the acute exposure.…”