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DOI: 10.1148/radiol.2483071686
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(Radiology 2008;248:852-859.)
© RSNA, 2008


Experimental Studies

DNA Double-Strand Breaks after Percutaneous Transluminal Angioplasty1

Dominik Geisel, MS, Johannes T. Heverhagen, PhD, MD, Marc Kalinowski, PhD, MD, and Hans-Joachim Wagner, PhD, MD

1 From the Department of Diagnostic Radiology, Philipps-University Marburg, Baldingerstrasse, 35043 Marburg, Germany. Received September 24, 2007; revision requested December 4; revision received December 19; accepted February 5, 2008; final version accepted February 20. Address correspondence to D.G. (e-mail: geiseld{at}med.uni-marburg.de).

Purpose: To determine exemplarily the amount of DNA damage and the repair kinetics after interventional radiologic procedures by using visualization of foci of the phosphorylated form of the H2AX histone variant ({gamma}H2AX) to quantify DNA double-strand breaks (DSBs) at percutaneous transluminal angioplasty (PTA) of the lower limb arteries.

Materials and Methods: After local ethics committee approval and written informed consent were obtained, five patients (two women, three men; mean age, 64.4 years; age range, 45–76 years) scheduled for computed tomography (CT) and 20 patients (six women, 14 men; mean age, 68.5 years; age range, 53–85 years) scheduled for PTA of lower limb arteries were prospectively entered into the study. Blood samples were taken before the first exposure to ionizing radiation and 5 minutes, 1 hour, 6 hours, and 24 hours after the last exposure. Additional samples were taken from the irradiated limb (femoral vein) of three patients who underwent PTA—before the first radiation exposure, 5 and 10 minutes after the first exposure, and 5 minutes after the last exposure. Lymphocytes were isolated, fixed, and stained with anti-{gamma}H2AX antibody, and {gamma}H2AX focus yields were determined with fluorescence microscopy. Data were analyzed with linear regression and two-sample F tests.

Results: Mean increase in number of {gamma}H2AX foci after CT (7.78 per 1 Gy · cm) depended linearly on dose-length product (r = 0.997). Number of foci reached background levels within 24 hours. Mean numbers of {gamma}H2AX foci per cell increased by factors of 4.08–20.67 in blood samples taken 5 minutes after PTA compared with mean numbers of foci before PTA. Mean radiation dose increase, 6.56/(10 Gy · cm2), depended linearly on dose-area product (r = 0.993). Maximal focus yield in cells taken directly from the irradiated limb was higher than that in cells from the systemic circulation (by mean factor of 1.46). Data showed compromised DSB repair capacity after PTA (P < .05). Mean number of foci at 24 hours (0.07 focus per cell) was significantly higher than mean number of foci in cell background (0.04 focus per cell, P < .05).

Conclusion: {gamma}H2AX focus formation can be used to determine in vivo induction of DNA DSBs after PTA. DSB repair capacity is compromised in patients who undergo PTA of lower limb arteries.

© RSNA, 2008