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Prediction of late normal tissue complications in RT treated gynaecological cancer patients: potential of the γ-H2AX foci assay and association with chromosomal radiosensitivity

Joke Werbrouck (UGent) , Kim De Ruyck (UGent) , Laurence Beels (UGent) , Anne Vral (UGent) , Marc Van Eijkeren (UGent) , Wilfried De Neve (UGent) and Hubert Thierens (UGent)
(2010) ONCOLOGY REPORTS. 23(2). p.571-578
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Abstract
In the present Study, the gamma-H2AX assay was investigated as a predictive test for the development of late normal tissue complications. Therefore, phosphorylated histone H2AX (gamma-H2AX) foci were scored in peripheral blood T-lymphocytes of gynaecological radiotherapy patients, irradiated in vitro with a high dose rate (HDR) and a low dose rate (LDR) protocol. The G(2) chromatid break assay was used to compare chromosomal radiation sensitivity with DNA doublestrand-break (DSB) repair capacity. Late normal tissue reactions were scored according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 scale. In our analyses, no differences in foci kinetics were found between the non to mild and moderate to severe patient groups after HDR irradiation. Furthermore, no relation was observed between the level of residual gamma-H2AX foci and CTC score after LDR irradiation. On the contrary, the number of chromatid breaks was associated with late clinical radiation sensitivity. Comparison of G(2) chromatid break assay data with the residual number of radiation-induced foci after LDR irradiation and repair times after HDR irradiation showed no relationship between the assays. From this study we can conclude that scoring of gamma-H2AX foci after in vitro irradiation of isolated T-lymphocytes of patients is not predictive for late radiotoxicity. This applies as well to the assessment of the repair kinetics after an HDR dose as to the determination of the number of residual foci after a LDR dose.
Keywords
late normal tissue complications, DNA DSB repair, gamma-H2AX foci, radiosensitivity assay, gynaecological cancer, POLYMORPHISMS, CELL-LINES, DSB REPAIR, X-RAYS, RADIOTHERAPY, IN-VITRO, RADIATION SENSITIVITY, HISTONE H2AX PHOSPHORYLATION, DOUBLE-STRAND BREAKS, PERIPHERAL-BLOOD LYMPHOCYTES

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Chicago
Werbrouck, Joke, Kim De Ruyck, Laurence Beels, Anne Vral, Marc Van Eijkeren, Wilfried De Neve, and Hubert Thierens. 2010. “Prediction of Late Normal Tissue Complications in RT Treated Gynaecological Cancer Patients: Potential of the γ-H2AX Foci Assay and Association with Chromosomal Radiosensitivity.” Oncology Reports 23 (2): 571–578.
APA
Werbrouck, Joke, De Ruyck, K., Beels, L., Vral, A., Van Eijkeren, M., De Neve, W., & Thierens, H. (2010). Prediction of late normal tissue complications in RT treated gynaecological cancer patients: potential of the γ-H2AX foci assay and association with chromosomal radiosensitivity. ONCOLOGY REPORTS, 23(2), 571–578.
Vancouver
1.
Werbrouck J, De Ruyck K, Beels L, Vral A, Van Eijkeren M, De Neve W, et al. Prediction of late normal tissue complications in RT treated gynaecological cancer patients: potential of the γ-H2AX foci assay and association with chromosomal radiosensitivity. ONCOLOGY REPORTS. 2010;23(2):571–8.
MLA
Werbrouck, Joke, Kim De Ruyck, Laurence Beels, et al. “Prediction of Late Normal Tissue Complications in RT Treated Gynaecological Cancer Patients: Potential of the γ-H2AX Foci Assay and Association with Chromosomal Radiosensitivity.” ONCOLOGY REPORTS 23.2 (2010): 571–578. Print.
@article{833328,
  abstract     = {In the present Study, the gamma-H2AX assay was investigated as a predictive test for the development of late normal tissue complications. Therefore, phosphorylated histone H2AX (gamma-H2AX) foci were scored in peripheral blood T-lymphocytes of gynaecological radiotherapy patients, irradiated in vitro with a high dose rate (HDR) and a low dose rate (LDR) protocol. The G(2) chromatid break assay was used to compare chromosomal radiation sensitivity with DNA doublestrand-break (DSB) repair capacity. Late normal tissue reactions were scored according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 scale. In our analyses, no differences in foci kinetics were found between the non to mild and moderate to severe patient groups after HDR irradiation. Furthermore, no relation was observed between the level of residual gamma-H2AX foci and CTC score after LDR irradiation. On the contrary, the number of chromatid breaks was associated with late clinical radiation sensitivity. Comparison of G(2) chromatid break assay data with the residual number of radiation-induced foci after LDR irradiation and repair times after HDR irradiation showed no relationship between the assays. From this study we can conclude that scoring of gamma-H2AX foci after in vitro irradiation of isolated T-lymphocytes of patients is not predictive for late radiotoxicity. This applies as well to the assessment of the repair kinetics after an HDR dose as to the determination of the number of residual foci after a LDR dose.},
  author       = {Werbrouck, Joke and De Ruyck, Kim and Beels, Laurence and Vral, Anne and Van Eijkeren, Marc and De Neve, Wilfried and Thierens, Hubert},
  issn         = {1021-335X},
  journal      = {ONCOLOGY REPORTS},
  keyword      = {late normal tissue complications,DNA DSB repair,gamma-H2AX foci,radiosensitivity assay,gynaecological cancer,POLYMORPHISMS,CELL-LINES,DSB REPAIR,X-RAYS,RADIOTHERAPY,IN-VITRO,RADIATION SENSITIVITY,HISTONE H2AX PHOSPHORYLATION,DOUBLE-STRAND BREAKS,PERIPHERAL-BLOOD LYMPHOCYTES},
  language     = {eng},
  number       = {2},
  pages        = {571--578},
  title        = {Prediction of late normal tissue complications in RT treated gynaecological cancer patients: potential of the \ensuremath{\gamma}-H2AX foci assay and association with chromosomal radiosensitivity},
  url          = {http://dx.doi.org/10.3892/or\_00000671},
  volume       = {23},
  year         = {2010},
}

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