BACKGROUND AND PURPOSE: 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. MATERIALS AND 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.
BACKGROUND AND PURPOSE: 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. MATERIALS AND 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.
Authors: Alesia N Ivashkevich; Olga A Martin; Andrea J Smith; Christophe E Redon; William M Bonner; Roger F Martin; Pavel N Lobachevsky Journal: Mutat Res Date: 2011-01-07 Impact factor: 2.433
Authors: Pavel Lobachevsky; Trevor Leong; Patricia Daly; Jai Smith; Nickala Best; Jonathan Tomaszewski; Ella R Thompson; Na Li; Ian G Campbell; Roger F Martin; Olga A Martin Journal: Cancer Lett Date: 2016-09-28 Impact factor: 8.679
Authors: William M Bonner; Christophe E Redon; Jennifer S Dickey; Asako J Nakamura; Olga A Sedelnikova; Stéphanie Solier; Yves Pommier Journal: Nat Rev Cancer Date: 2008-11-13 Impact factor: 60.716