PMID- 29492301
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240316
IS  - 2058-5888 (Print)
IS  - 2058-5888 (Electronic)
IS  - 2058-5888 (Linking)
VI  - 2
IP  - 4
DP  - 2016 Dec
TI  - Fractionated low-dose exposure to ionizing radiation leads to DNA damage, 
      epigenetic dysregulation, and behavioral impairment.
PG  - dvw025
LID - 10.1093/eep/dvw025 [doi]
LID - dvw025
AB  - Studies of Fractionated Exposure to Low Doses of Ionizing Radiation (FELDIR) has 
      become of increasing importance to clinical interventions. Its consequences on 
      DNA damage, physical, and mental health have been insufficiently investigated, 
      however. The goal of this study was to determine the effects of FELDIR on the 
      brain using a mouse model. We addressed the levels of DNA damage, global genomic 
      methylation, and DNA methylation machinery in cerebellum, frontal lobe, olfactory 
      bulb and hippocampal tissues, as well as behavioral changes linked to FELDIR 
      exposure. The results reveal increased levels of DNA damage, as reflected by 
      increased occurrence of DNA Strand Breaks (SBs) and dysregulation of 
      stress-response kinase p38. FELDIR also resulted in initial loss of global 
      genomic methylation and altered expression of methyltransferases DNMT1 
      (down-regulation) and DNMT3a (up-regulation), as well as methyl-binding protein 
      MeCP2 (up-regulation). FELDIR-associated behavioral changes included impaired 
      skilled limb placement on a ladder rung task, increased rearing activity in an 
      open field, and elevated anxiety-like behaviors. The said alterations showed 
      significant dose and tissue specificity. Thus, FELDIR represents a critical 
      impact on DNA integrity and behavioral outcomes that need to be considered in the 
      design of clinical intervention studies.
FAU - Koturbash, Igor
AU  - Koturbash I
AD  - Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, 
      Canada T1K3M4.
FAU - Jadavji, Nafisa M
AU  - Jadavji NM
AD  - Department of Neuroscience, University of Lethbridge, Lethbridge, AB, Canada 
      T1K3M4.
FAU - Kutanzi, Kristy
AU  - Kutanzi K
AD  - Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, 
      Canada T1K3M4.
FAU - Rodriguez-Juarez, Rocio
AU  - Rodriguez-Juarez R
AD  - Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, 
      Canada T1K3M4.
FAU - Kogosov, Dmitry
AU  - Kogosov D
AD  - Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, 
      Canada T1K3M4.
FAU - Metz, Gerlinde A S
AU  - Metz GAS
AD  - Department of Neuroscience, University of Lethbridge, Lethbridge, AB, Canada 
      T1K3M4.
AD  - Alberta Epigenetics Network, Calgary, AB, Canada.
FAU - Kovalchuk, Olga
AU  - Kovalchuk O
AD  - Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, 
      Canada T1K3M4.
AD  - Alberta Epigenetics Network, Calgary, AB, Canada.
LA  - eng
GR  - KL2 TR000063/TR/NCATS NIH HHS/United States
GR  - P20 GM109005/GM/NIGMS NIH HHS/United States
GR  - UL1 TR000039/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20170131
PL  - England
TA  - Environ Epigenet
JT  - Environmental epigenetics
JID - 101675941
PMC - PMC5804539
OTO - NOTNLM
OT  - DNA damage
OT  - behavioral impairment
OT  - epigenetics
OT  - low-dose ionizing radiation
EDAT- 2017/01/31 00:00
MHDA- 2017/01/31 00:01
PMCR- 2017/01/31
CRDT- 2018/03/02 06:00
PHST- 2016/08/04 00:00 [received]
PHST- 2016/10/25 00:00 [revised]
PHST- 2016/10/27 00:00 [accepted]
PHST- 2018/03/02 06:00 [entrez]
PHST- 2017/01/31 00:00 [pubmed]
PHST- 2017/01/31 00:01 [medline]
PHST- 2017/01/31 00:00 [pmc-release]
AID - dvw025 [pii]
AID - 10.1093/eep/dvw025 [doi]
PST - epublish
SO  - Environ Epigenet. 2017 Jan 31;2(4):dvw025. doi: 10.1093/eep/dvw025. eCollection 
      2016 Dec.