title: Leukocyte DNA damage after multi-detector row CT: a quantitative biomarker of low-level radiation exposure.
abstract: OBJECTIVE
  To prospectively determine if gammaH2AX (phosphorylated form of H2AX histone variant)-based visualization and quantification of DNA damage induced in peripheral blood mononuclear cells (PBMCs) can be used to estimate the radiation dose received by adult patients who undergo multidetector computed tomography (CT).
  
  
  METHODS
  After institutional review board approval and written informed patient consent were obtained, eight women and five men (mean age, 63.8 years) who would be undergoing chest-abdominal-pelvic CT or chest CT only were recruited. Venous blood samples obtained before scanning were exposed to different radiation doses in vitro and incubated for 5-30 minutes to obtain reference values of gammaH2AX focus yield. Additional blood samples were taken 5-30 minutes after CT. Leukocytes were isolated, fixed, and stained for gammaH2AX expression. The gammaH2AX focus yields were determined with fluorescence microscopy, and the radiation doses delivered during CT were estimated by comparing post-CT focus yields with in vitro pre-CT focus yields. These CT radiation doses were compared with doses calculated by using phantom dosimetry and Monte Carlo data sets. Data were analyzed by using linear regression, the dispersion index test, and the contaminated Poisson method.
  
  
  RESULTS
  Compared with the gammaH2AX focus yields in blood samples taken before CT (0.06 focus per cell+/-0.01 [mean+/-standard error of mean]), the yields in blood samples taken 5 minutes after chest-abdominal-pelvic CT (0.52 focus per cell+/-0.02) were 8-10-fold higher and corresponded to a mean radiation dose of 16.4 mGy (95% confidence interval: 15.1, 17.7). The mean yield of 0.24 focus per cell+/-0.04 in one patient after chest CT corresponded to a mean radiation dose of 6.3 mGy+/-1.4. In comparison, phantom dosimetry-calculated total blood doses were 13.85 mGy with whole-body CT and 5.16 mGy with chest CT.
  
  
  CONCLUSIONS
  gammaH2AX focus yield in blood cells may be a useful quantitative biomarker of human low-level radiation exposure.
authors.affiliation: Department of Radiation Oncology & Biology, University of Oxford, and Paul Strickland Scanner Cancer Centre, Mount Vernon Hospital, Middlesex, England. rothkamm@gci.ac.uk
authors.forename: Kai
authors.initials: K
authors.lastname: Rothkamm
authors.forename: Sheena
authors.initials: S
authors.lastname: Balroop
authors.forename: Jane
authors.initials: J
authors.lastname: Shekhdar
authors.forename: Patricia
authors.initials: P
authors.lastname: Fernie
authors.forename: Vicky
authors.initials: V
authors.lastname: Goh
mesh_terms: D000368:Aged; D015415:Biomarkers; D004247:DNA / Q000235:genetics* / Q000528:radiation effects*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D011829:Radiation Dosage; D014057:Tomography, X-Ray Computed / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D004247:DNA