title: The effect of genetic background and dose on non-targeted effects of radiation.
abstract: OBJECTIVE
  This work investigates the hypothesis that genetic background plays a significant role in the signalling mechanisms underlying induction and perpetuation of genomic instability following radiation exposure.
  
  
  METHODS
  Bone marrow from two strains of mice (CBA and C57) were exposed to a range of X-ray doses (0, 0.01, 0.1, 1 and 3 Gy). Different cellular signalling endpoints: Apoptosis, cytokine levels and calcium flux, were evaluated at 2 h, 24 h and 7 d post-irradiation to assess immediate and delayed effects.
  
  
  RESULTS
  In CBA (radiosensitive) elevated apoptosis levels were observed at 24 h post X-irradiation, and transforming growth factor-β (TGF-β) levels which increased with time and dose. C57 showed a higher background level of apoptosis, and sustained apoptotic levels 7 days after radiation exposure. Levels of tumor necrosis factor-α (TNF-α were increased in C57 at day 7 for higher X-ray doses. TGF-β levels were higher in CBA, whilst C57 exhibited a greater TNF-α response. Calcium flux was induced in reporter cells on exposure to conditioned media from both strains.
  
  
  CONCLUSIONS
  These results show genetic and dose specific differences in radiation-induced signalling in the initiation and perpetuation of the instability process, which have potential implications on evaluation of non-targeted effects in radiation risk assessment.
authors.affiliation: Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Irons
authors.forename: Virginia
authors.initials: V
authors.lastname: Serra
authors.forename: Deborah
authors.initials: D
authors.lastname: Bowler
authors.forename: Kim
authors.initials: K
authors.lastname: Chapman
authors.forename: Stefania
authors.initials: S
authors.lastname: Militi
authors.forename: Fiona
authors.initials: F
authors.lastname: Lyng
authors.forename: Munira
authors.initials: M
authors.lastname: Kadhim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D024201:Bystander Effect / Q000235:genetics* / Q000528:radiation effects*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D020022:Genetic Predisposition to Disease; D042822:Genomic Instability / Q000528:radiation effects*; D018499:Linear Energy Transfer; D008297:Male; D051379:Mice; D011836:Radiation Tolerance / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000235:genetics* / Q000528:radiation effects*; D013045:Species Specificity; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014965:X-Rays / Q000009:adverse effects
chemical_list: D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium