Late residual gamma-H2AX foci in murine skin are dose responsive and predict radiosensitivity in vivo.
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.
Bhogal
Nirmal
N
Applied Molecular Oncology and Radiation Medicine Program, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Ontario, Canada.
Kaspler
Pavel
P
Jalali
Farid
F
Hyrien
Ollivier
O
Chen
Rui
R
Hill
Richard P
RP
Bristow
Robert G
RG
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
D006657:Histones; C475961:gamma-H2AX protein, mouse