gamma-H2AX foci formation in peripheral blood lymphocytes of tumor patients after local radiotherapy to different sites of the body: dependence on the dose-distribution, irradiated site and time from start of treatment.
OBJECTIVE
To evaluate the relationship between an estimated integral total body radiation dose delivered and phosphorylated histone H2AX protein (gamma-H2AX) foci formation in peripheral blood lymphocytes of cancer patients.


METHODS
gamma-H2AX formation was quantified as the mean number of foci per lymphocyte (N(meanH2AX)) and the percentage of lymphocytes with > or =n foci. The integrated total body radiation dose was estimated from the dose volume histogram of patient's body corrected for the proportion of the body scanned by computed tomography for 3D treatment planning.


RESULTS
There was a strong linear correlation between the mean number of gamma-H2AX foci per lymphocyte in the peripheral blood sample and integrated total body radiation dose (r = 0.83, p < 0.0001). The slope of the relationship was dependent on the site of body irradiated. In comparison to chest irradiation with a slope of 8.7 +/- 0.8 foci Gy(-1), the slopes for brain, upper leg and pelvic sites were significantly shallower by -4.7, -4.3, and -3.8 Gy(-1), respectively (p < 0.0001), while the slope for upper abdomen irradiation was significantly larger by 9.1 +/- 2.6 Gy(-1) (p = 0.0007). There was a slight time effect since the start of radiotherapy on the slopes of the in vivo dose responses leading to shallower slopes (-1.5 +/- 0.7 Gy(-1), p = 0.03) later (> or =10 day) during radiotherapy. After in vitro irradiation, lymphocytes showed 10.41 +/- 0.12 foci per Gy with no evidence of inter-individual heterogeneity.


CONCLUSIONS
gamma-H2AX measurements in peripheral lymphocytes after local radiotherapy allow the estimation of the applied integral body dose. The site and time dependence have to be considered.
Sak
Ali
A
Department of Radiotherapy, University Hospital Essen, Essen, Germany. ali.sak@uni-duisburg-essen.de
Grehl
Sara
S
Erichsen
Patricia
P
Engelhard
Marianne
M
Grannass
Andreas
A
Levegrün
Sabine
S
Pöttgen
Christoph
C
Groneberg
Michael
M
Stuschke
Martin
M
D000005:Abdomen / Q000473:pathology / Q000528:radiation effects*; D001921:Brain / Q000473:pathology / Q000528:radiation effects*; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D006657:Histones / Q000097:blood*; D006801:Humans; D007866:Leg / Q000473:pathology / Q000528:radiation effects*; D008214:Lymphocytes / Q000097:blood / Q000528:radiation effects*; D010388:Pelvis / Q000473:pathology / Q000528:radiation effects*; D011836:Radiation Tolerance; D011880:Radiotherapy Planning, Computer-Assisted / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods; D013997:Time Factors
C468783:H2AX protein, human; D006657:Histones