The use of gamma-H2AX as a biodosimeter for total-body radiation exposure in non-human primates.
BACKGROUND
There is a crucial shortage of methods capable of determining the extent of accidental exposures of human beings to ionizing radiation. However, knowledge of individual exposures is essential for early triage during radiological incidents to provide optimum possible life-sparing medical procedures to each person.


RESULTS
We evaluated immunocytofluorescence-based quantitation of γ-H2AX foci as a biodosimeter of total-body radiation exposure ((60)Co γ-rays) in a rhesus macaque (Macaca mulatta) model. Peripheral blood lymphocytes and plucked hairs were collected from 4 cohorts of macaques receiving total body irradiation doses ranging from 1 Gy to 8.5 Gy. Each cohort consisted of 6 experimental and 2 control animals. Numbers of residual γ-H2AX foci were proportional to initial irradiation doses and statistically significant responses were obtained until 1 day after 1 Gy, 4 days after 3.5 and 6.5 Gy, and 14 days after 8.5 Gy in lymphocytes and until 1 day after 1 Gy, at least 2 days after 3.5 and 6.5 Gy, and 9 days after 8.5 Gy in plucked hairs.


CONCLUSIONS
These findings indicate that quantitation of γ-H2AX foci may make a robust biodosimeter for analyzing total-body exposure to ionizing radiation in humans. This tool would help clinicians prescribe appropriate types of medical intervention for optimal individual outcome. These results also demonstrate that the use of a high throughput γ-H2AX biodosimeter would be useful for days post-exposure in applications like large-scale radiological events or radiation therapy. In addition, this study validates a possibility to use plucked hair in future clinical trials investigating genotoxic effects of drugs and radiation treatments.
Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. redonc@mail.nih.gov
Christophe E
CE
Redon
Asako J
AJ
Nakamura
Ksenia
K
Gouliaeva
Arifur
A
Rahman
William F
WF
Blakely
William M
WM
Bonner
D000328:Adult; D000368:Aged; D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D006197:Hair / Q000378:metabolism / Q000528:radiation effects*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D011832:Radiation Injuries / Q000175:diagnosis / Q000378:metabolism; D011874:Radiometry / Q000379:methods; D014916:Whole-Body Irradiation
C468783:H2AX protein, human; D006657:Histones