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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.

SUBMITTER: Newman MR

PROVIDER: S-EPMC3968115 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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A single whole-body low dose X-irradiation does not affect L1, B1 and IAP repeat element DNA methylation longitudinally.

Newman Michelle R MR Sykes Pamela J PJ Blyth Benjamin J BJ Bezak Eva E Lawrence Mark D MD Morel Katherine L KL Ormsby Rebecca J RJ

PloS one 20140327 3

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), ...[more]

PMID: 24676381

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Project description:High-dose ionizing irradiation can cause extensive injuries in susceptible tissues. A noninvasive imaging technique that detects a surrogate marker of apoptosis may help characterize the dynamics of radiation-induced tissue damage. The goal of this study was to prove the concept of imaging the temporal and spatial distribution of damage in susceptible tissues after high-dose radiation exposure, using (99m)Tc-duramycin as a phosphatidylethanolamine-binding radiopharmaceutical.Rats were subjected to 15 Gy of total-body irradiation with x-rays. Planar whole-body (99m)Tc-duramycin scanning (n = 4 per time point) was conducted at 24, 48, and 72 h using a clinical ?-camera. On the basis of findings from planar imaging, preclinical SPECT data were acquired on control rats and on irradiated rats at 6 and 24 h after irradiation (n = 4 per time point). Imaging data were validated by ?-counting and histology, using harvested tissues in parallel groups of animals (n = 4).Prominent focal uptake was detected in the thymus as early as 6 h after irradiation, followed by a gradual decline in (99m)Tc-duramycin binding accompanied by extensive thymic atrophy. Early (6-24 h) radioactivity uptake in the gastrointestinal region was detected. Significant signal was seen in major bones in a slightly delayed fashion, at 24 h, which persisted for at least 2 d. This finding was paralleled by an elevation in signal intensity in the kidneys, spleen, and liver. The imaging results were consistent with ex vivo ?-counting results and histology. Relatively high levels of apoptosis were detected from histology in the thymus, guts, and bones, with the thymus undergoing substantial atrophy.As a proof of principle, this study demonstrated a noninvasive imaging technique that allows characterization of the temporal and spatial dynamics of injuries in susceptible tissues during the acute phase after high-dose ionizing irradiation. Such an imaging capability will potentially be useful for global, whole-body, assessment of tissue damage after radiation exposure. These data, in turn, will contribute to our general knowledge of tissue susceptibility to ionizing irradiation, as well as the onset and progression of tissue injuries.

Dataset Information

A single whole-body low dose X-irradiation does not affect L1, B1 and IAP repeat element DNA methylation longitudinally.

Publications

A single whole-body low dose X-irradiation does not affect L1, B1 and IAP repeat element DNA methylation longitudinally.

Similar Datasets

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