title: Late residual gamma-H2AX foci in murine skin are dose responsive and predict radiosensitivity in vivo.
abstract: Accurate biodosimetry is needed to estimate radiation doses received in vivo from accidental or unwarranted radiation exposures. We investigated the use of DNA repair foci (e.g. gamma-H2AX) at late times after irradiation in vivo as a biodosimeter of initial ionizing radiation dose. Two radiosensitive strains (SCID and BALB/c) and two radioresistant strains (C57BL/6 and C3H/HeJ) were used to quantify gamma-H2AX foci in a skin tissue microarray after doses of 1 to 10 Gy at early and late times after irradiation (1 and 7 days). Using a 3D quantitative immunofluorescence microscopy analysis, we observed a dose response for gamma-H2AX foci for all strains at 30 min, 24 h and 7 days after irradiation. The numbers of residual foci were significantly different between each of the four strains and reflected the relative radiosensitivity in vivo. In comparing gamma-H2AX focus and micronucleus formation after irradiation, we also observed association between the number of micronuclei and number of foci after 1 and 7 days between radiosensitive and radioresistant strains. We conclude that 3D image analysis of gamma-H2AX in skin can be used to detect relative radiosensitivity based on late residual gamma-H2AX foci. This technique may be a useful biodosimeter to determine dose at times up to 1 week after accidental or catastrophic radiation exposure in vivo.
authors.affiliation: Applied Molecular Oncology and Radiation Medicine Program, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Ontario, Canada.
authors.forename: Nirmal
authors.initials: N
authors.lastname: Bhogal
authors.forename: Pavel
authors.initials: P
authors.lastname: Kaspler
authors.forename: Farid
authors.initials: F
authors.lastname: Jalali
authors.forename: Ollivier
authors.initials: O
authors.lastname: Hyrien
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Richard P
authors.initials: RP
authors.lastname: Hill
authors.forename: Robert G
authors.initials: RG
authors.lastname: Bristow
mesh_terms: D000818:Animals; D001706:Biopsy; D004260:DNA Repair / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004781:Environmental Exposure; D006657:Histones / Q000378:metabolism*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D051379:Mice; D011836:Radiation Tolerance; D011874:Radiometry; D015203:Reproducibility of Results; D012867:Skin / Q000166:cytology / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects*; D013045:Species Specificity; D023481:Terrorism; D013997:Time Factors; D046888:Tissue Array Analysis
chemical_list: D006657:Histones; C475961:gamma-H2AX protein, mouse