title: Prediction of late normal tissue complications in RT treated gynaecological cancer patients: potential of the gamma-H2AX foci assay and association with chromosomal radiosensitivity.
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 G2 chromatid break assay was used to compare chromosomal radiation sensitivity with DNA double-strand-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 G2 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.
authors.affiliation: Department of Basic Medical Sciences, Ghent University, Ghent, Belgium. joke.werbrouck@ugent.be
authors.forename: Joke
authors.initials: J
authors.lastname: Werbrouck
authors.forename: Kim
authors.initials: K
authors.lastname: De Ruyck
authors.forename: Laurence
authors.initials: L
authors.lastname: Beels
authors.forename: Anne
authors.initials: A
authors.lastname: Vral
authors.forename: Marc
authors.initials: M
authors.lastname: Van Eijkeren
authors.forename: Wilfried
authors.initials: W
authors.lastname: De Neve
authors.forename: Hubert
authors.initials: H
authors.lastname: Thierens
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics / Q000532:radiotherapy*; D002877:Chromosomes, Human / Q000528:radiation effects; D005260:Female; D005500:Follow-Up Studies; D005833:Genital Neoplasms, Female / Q000175:diagnosis / Q000235:genetics / Q000532:radiotherapy*; D006657:Histones / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods; D011379:Prognosis; D011832:Radiation Injuries / Q000175:diagnosis*; D011836:Radiation Tolerance / Q000235:genetics*; D011878:Radiotherapy / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D012307:Risk Factors; D013997:Time Factors; D014410:Tumor Stem Cell Assay
chemical_list: C468783:H2AX protein, human; D006657:Histones