Leukocyte DNA damage after multi-detector row CT: a quantitative biomarker of low-level radiation exposure.

PURPOSE 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). MATERIALS AND 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. CONCLUSION gammaH2AX focus yield in blood cells may be a useful quantitative biomarker of human low-level radiation exposure.

[1]  Kai Rothkamm,et al.  A Double-Strand Break Repair Defect in ATM-Deficient Cells Contributes to Radiosensitivity , 2004, Cancer Research.

[2]  T. Halazonetis,et al.  P53 Binding Protein 1 (53bp1) Is an Early Participant in the Cellular Response to DNA Double-Strand Breaks , 2000, The Journal of cell biology.

[3]  Junjie Chen,et al.  Accumulation of Checkpoint Protein 53BP1 at DNA Breaks Involves Its Binding to Phosphorylated Histone H2AX* , 2003, Journal of Biological Chemistry.

[4]  R. Doll,et al.  Cancer risks attributable to low doses of ionizing radiation: Assessing what we really know , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Michael Uder,et al.  In vivo formation and repair of DNA double-strand breaks after computed tomography examinations. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Kai Rothkamm,et al.  Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[7]  David J Brenner,et al.  Estimated radiation risks potentially associated with full-body CT screening. , 2004, Radiology.

[8]  R. Nicholson,et al.  Primary radiation outside the imaged volume of a multislice helical CT scan. , 2002, The British journal of radiology.

[9]  E. Rogakou,et al.  Megabase Chromatin Domains Involved in DNA Double-Strand Breaks in Vivo , 1999, The Journal of cell biology.

[10]  L Roy,et al.  Review of translocations detected by FISH for retrospective biological dosimetry applications. , 2005, Radiation protection dosimetry.

[11]  Amy Berrington de González,et al.  Risk of cancer from diagnostic X-rays: estimates for the UK and 14 other countries , 2004, The Lancet.

[12]  P. Dawson Patient dose in multislice CT: why is it increasing and does it matter? , 2004, The British journal of radiology.

[13]  S. Jackson,et al.  Sensing and repairing DNA double-strand breaks. , 2002, Carcinogenesis.

[14]  D. Lloyd,et al.  A collaborative exercise on cytogenetic dosimetry for simulated whole and partial body accidental irradiation. , 1987, Mutation research.

[15]  D. Tripodi,et al.  Separation of peripheral leukocytes by Ficoll density gradient centrifugation. , 1971, Transplantation.

[16]  M. Kalra,et al.  Techniques and applications of automatic tube current modulation for CT. , 2004, Radiology.

[17]  M. Bauchinger,et al.  Quantification of low-level radiation exposure by conventional chromosome aberration analysis. , 1995, Mutation research.

[18]  A K Dixon,et al.  16-detector multislice CT: dosimetry estimation by TLD measurement compared with Monte Carlo simulation. , 2004, The British journal of radiology.

[19]  M Mahesh,et al.  Dose and pitch relationship for a particular multislice CT scanner. , 2001, AJR. American journal of roentgenology.

[20]  P. Jeggo,et al.  Radiation-induced genomic rearrangements formed by nonhomologous end-joining of DNA double-strand breaks. , 2001, Cancer research.