DNA double-strand breaks after percutaneous transluminal angioplasty.
OBJECTIVE
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 (gammaH2AX) to quantify DNA double-strand breaks (DSBs) at percutaneous transluminal angioplasty (PTA) of the lower limb arteries.


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-gammaH2AX antibody, and gammaH2AX focus yields were determined with fluorescence microscopy. Data were analyzed with linear regression and two-sample F tests.


RESULTS
Mean increase in number of gammaH2AX foci after CT (7.78 per 1 Gy x cm) depended linearly on dose-length product (r = 0.997). Number of foci reached background levels within 24 hours. Mean numbers of gammaH2AX 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 x cm(2)), 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).


CONCLUSIONS
GammaH2AX 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.
Geisel
Dominik
D
Department of Diagnostic Radiology, Philipps-University Marburg, Baldingerstrasse, 35043 Marburg, Germany. geiseld@med.uni-marburg.de
Heverhagen
Johannes T
JT
Kalinowski
Marc
M
Wagner
Hans-Joachim
HJ
D000368:Aged; D000792:Angiography / Q000009:adverse effects*; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D001158:Arteries / Q000528:radiation effects* / Q000601:surgery*; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects*; D005260:Female; D006801:Humans; D035002:Lower Extremity / Q000098:blood supply / Q000000981:diagnostic imaging / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015641:Radiography, Interventional / Q000009:adverse effects*; D014057:Tomography, X-Ray Computed / Q000009:adverse effects