title: 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.
authors.affiliation: Flinders Centre for Innovation in Cancer, Flinders University and Medical Centre, Bedford Park, South Australia, Australia.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Newman
authors.affiliation: Flinders Centre for Innovation in Cancer, Flinders University and Medical Centre, Bedford Park, South Australia, Australia.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Sykes
authors.affiliation: Flinders Centre for Innovation in Cancer, Flinders University and Medical Centre, Bedford Park, South Australia, Australia.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Blyth
authors.affiliation: Department of Medical Physics, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
authors.forename: Eva
authors.initials: E
authors.lastname: Bezak
authors.affiliation: Flinders Centre for Innovation in Cancer, Flinders University and Medical Centre, Bedford Park, South Australia, Australia.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Lawrence
authors.affiliation: Flinders Centre for Innovation in Cancer, Flinders University and Medical Centre, Bedford Park, South Australia, Australia.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Morel
authors.affiliation: Flinders Centre for Innovation in Cancer, Flinders University and Medical Centre, Bedford Park, South Australia, Australia.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Ormsby
mesh_terms: D000367:Age Factors; D000818:Animals; D019175:DNA Methylation / Q000528:radiation effects*; D005260:Female; D007426:Genes, Intracisternal A-Particle / Q000528:radiation effects*; D008099:Liver / Q000378:metabolism / Q000528:radiation effects; D020084:Long Interspersed Nucleotide Elements / Q000528:radiation effects*; D008297:Male; D051379:Mice; D023421:Models, Animal; D011829:Radiation Dosage; D012091:Repetitive Sequences, Nucleic Acid / Q000528:radiation effects; D013154:Spleen / Q000378:metabolism / Q000528:radiation effects; D014916:Whole-Body Irradiation; D014965:X-Rays