Residual gammaH2AX after irradiation of human lymphocytes and monocytes in vitro and its relation to late effects after prostate brachytherapy.
OBJECTIVE
Retention of gammaH2AX foci in irradiated cells can signify a deficiency in DNA double-strand break repair that may be useful as an indicator of individual radiosensitivity.


METHODS
To examine this possibility, the retention of gammaH2AX after irradiation was compared using white blood cells from 20 prostate brachytherapy patients who developed late normal tissue toxicity and 20 patients with minimal toxicity. Peripheral blood lymphocytes and monocytes were coded for analysis, exposed in vitro to 4 doses of 0.7 Gy X-rays at 3 hourly intervals, and retention of gammaH2AX was measured by flow cytometry 18 hours after the final irradiation.


RESULTS
Excellent reproducibility in duplicate samples and a range in residual gammaH2AX from 7% above background to 244% above background were observed. Residual gammaH2AX in lymphocytes showed a positive correlation with patient age. However, no relation was observed between the level of residual gammaH2AX in peripheral blood mononuclear cells and late normal tissue damage.


CONCLUSIONS
We conclude that the method of detection of residual gammaH2AX after in vitro irradiation of lymphocytes and monocytes was simple, reproducible, and sensitive. However, it failed to predict for late normal tissue toxicity after brachytherapy. Possible reasons are discussed.
Olive
Peggy L
PL
Medical Biophysics Department, British Columbia Cancer Research Centre, BC, Canada. polive@bccrc.ca
Banáth
Judit P
JP
Keyes
Mira
M
D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy; D053903:DNA Breaks, Double-Stranded; D006657:Histones / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000378:metabolism* / Q000528:radiation effects; D008297:Male; D009000:Monocytes / Q000378:metabolism* / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000528:radiation effects; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013997:Time Factors; D014965:X-Rays / Q000009:adverse effects*
C468783:H2AX protein, human; D006657:Histones