title: Integrated molecular analysis indicates undetectable change in DNA damage in mice after continuous irradiation at ~ 400-fold natural background radiation.
abstract: BACKGROUND
  In the event of a nuclear accident, people are exposed to elevated levels of continuous low dose-rate radiation. Nevertheless, most of the literature describes the biological effects of acute radiation.
  
  
  OBJECTIVE
  DNA damage and mutations are well established for their carcinogenic effects. We assessed several key markers of DNA damage and DNA damage responses in mice exposed to low dose-rate radiation to reveal potential genotoxic effects associated with low dose-rate radiation.
  
  
  METHODS
  We studied low dose-rate radiation using a variable low dose-rate irradiator consisting of flood phantoms filled with 125Iodine-containing buffer. Mice were exposed to 0.0002 cGy/min (~ 400-fold background radiation) continuously over 5 weeks. We assessed base lesions, micronuclei, homologous recombination (HR; using fluorescent yellow direct repeat mice), and transcript levels for several radiation-sensitive genes.
  
  
  RESULTS
  We did not observe any changes in the levels of the DNA nucleobase damage products hypoxanthine, 8-oxo-7,8-dihydroguanine, 1,N6-ethenoadenine, or 3,N4-ethenocytosine above background levels under low dose-rate conditions. The micronucleus assay revealed no evidence that low dose-rate radiation induced DNA fragmentation, and there was no evidence of double strand break-induced HR. Furthermore, low dose-rate radiation did not induce Cdkn1a, Gadd45a, Mdm2, Atm, or Dbd2. Importantly, the same total dose, when delivered acutely, induced micronuclei and transcriptional responses.
  
  
  CONCLUSIONS
  These results demonstrate in an in vivo animal model that lowering the dose-rate suppresses the potentially deleterious impact of radiation and calls attention to the need for a deeper understanding of the biological impact of low dose-rate radiation.
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Werner
authors.initials: W
authors.lastname: Olipitz
authors.forename: Dominika
authors.initials: D
authors.lastname: Wiktor-Brown
authors.forename: Joe
authors.initials: J
authors.lastname: Shuga
authors.forename: Bo
authors.initials: B
authors.lastname: Pang
authors.forename: Jose
authors.initials: J
authors.lastname: McFaline
authors.forename: Pallavi
authors.initials: P
authors.lastname: Lonkar
authors.forename: Aline
authors.initials: A
authors.lastname: Thomas
authors.forename: James T
authors.initials: JT
authors.lastname: Mutamba
authors.forename: Joel S
authors.initials: JS
authors.lastname: Greenberger
authors.forename: Leona D
authors.initials: LD
authors.lastname: Samson
authors.forename: Peter C
authors.initials: PC
authors.lastname: Dedon
authors.forename: Jacquelyn C
authors.initials: JC
authors.lastname: Yanch
authors.forename: Bevin P
authors.initials: BP
authors.lastname: Engelward
mesh_terms: D000818:Animals; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D020869:Gene Expression Profiling; D051379:Mice; D008810:Mice, Inbred C57BL