title: Biodosimetry using radiation-induced micronuclei in skin fibroblasts.
abstract: OBJECTIVE
  We assessed micronuclei in dermal fibroblasts as a local biodosimeter for estimating accidental in vivo radiation exposure.
  
  
  METHODS
  Male and female C3H/HeJ and C57Bl6 mice of four age groups (∼11, 36, 60 and 99 weeks) received a single whole body dose of gamma radiation (0-10 Gy) and radiation-induced micronuclei per 1,000 binucleated cells were assessed in skin fibroblasts in their first division after isolation from biopsies taken on days 1 and 7 post irradiation. The method of generalized estimating equations was used for statistical analyses.
  
  
  RESULTS
  Total micronuclei were increased on day 1 in a dose-dependent manner in the range of 1-10 Gy, with no significant attenuation of response between day 1 and day 7 and no significant effect of gender. Between-strain differences were observed with C3H/HeJ mice showing lower background micronuclei and a slightly steeper dose response. Age affected only the background micronuclei (moderate increase with age). The model demonstrated that the assay yields 'unbiased' prediction of the dose between 0 and 7 Gy. Within this dose range, the predicted dose was found to be accurate within ±1.5-2 Gy. When the specificity is set to 95%, the assay can distinguish between unexposed and 2 Gy exposed mice with a sensitivity of around 60%. The sensitivity approached 100% when discriminating between unexposed mice and mice receiving doses equal to or greater than 4 Gy. The percentage of binucleated cells with micronuclei was shown to be useful as a simpler and slightly faster substitute for the total micronuclei count.
  
  
  CONCLUSIONS
  Micronuclei in dermal fibroblasts isolated up to 1 week after irradiation can be a useful biodosimeter for local dose after accidental radiation exposure.
authors.affiliation: Ontario Cancer Institute/Princess Margaret Hospital, University Health Network and Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada.
authors.forename: Pavel
authors.initials: P
authors.lastname: Kaspler
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Ollivier
authors.initials: O
authors.lastname: Hyrien
authors.forename: Salomeh
authors.initials: S
authors.lastname: Jelveh
authors.forename: Robert G
authors.initials: RG
authors.lastname: Bristow
authors.forename: Richard P
authors.initials: RP
authors.lastname: Hill
mesh_terms: D000818:Animals; D001681:Biological Assay / Q000379:methods*; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D048629:Micronuclei, Chromosome-Defective / Q000528:radiation effects*; D015162:Micronucleus Tests / Q000379:methods*; D011829:Radiation Dosage; D011874:Radiometry / Q000379:methods*; D012879:Skin Physiological Phenomena / Q000528:radiation effects*; D014916:Whole-Body Irradiation