Double strand break induction and kinetics indicate preserved hypersensitivity in keratinocytes to subtherapeutic doses for 7weeks of radiotherapy
| Autor: | Majlis Book, Ingegerd Hermansson, Ingela Turesson, Jan Nyman, Martin Simonsson, Fredrik Qvarnström, Karl-Axel Johansson |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Keratinocytes Male Pathology medicine.medical_specialty medicine.medical_treatment Biopsy Fluorescent Antibody Technique Immunofluorescence Radiation Tolerance 03 medical and health sciences Prostate cancer 0302 clinical medicine medicine Humans Radiology Nuclear Medicine and imaging DNA Breaks Double-Stranded Skin Double strand medicine.diagnostic_test Epidermis (botany) business.industry Prostatic Neoplasms Dose-Response Relationship Radiation Hematology medicine.disease Radiation therapy Kinetics 030104 developmental biology Oncology 030220 oncology & carcinogenesis Digital image analysis Immunohistochemistry Radiotherapy treatment Dose Fractionation Radiation business |
| Zdroj: | Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 122(1) |
| ISSN: | 1879-0887 |
| Popis: | Background and purpose Previously we reported that hyper-radiosensitivity (HRS) was evidenced by quantifying DNA double strand break (DSB) foci in epidermis biopsies collected after delivering radiotherapeutic one and five dose fractions. The aim of this study was to determine whether HRS was preserved throughout a 7-week radiotherapy treatment, and also to examine the rate of foci decline and foci persistence between dose fractions. Materials and methods 42 patients with prostate cancer received 7-week fractionated radiotherapy treatment (RT) with daily dose fractions of 0.05–1.10Gy to the skin. Before RT, and at several times throughout treatment, skin biopsies ( n =452) were collected at 30min, and 2, 3, 24, and 72h after dose fractions. DSB-foci markers, γH2AX and 53BP1, were labelled in epidermal keratinocytes with immunofluorescence and immunohistochemical staining. Foci were counted both with digital image analysis and manually. Results HRS in keratinocytes was evidenced by the dose–response relationships of DSB foci, observed throughout the treatment course, independent of sampling time and quantification method. Foci observed at 24h after dose fractions indicated considerable DSB persistence. Accordingly, foci significantly accumulated after 5 consecutive dose fractions. For doses below 0.3Gy, persistent foci could be observed even at 72h after damage induction. A comparison of γH2AX and 53BP1 quantifications in double-stained biopsies showed similar HRS dose–response relationships. Conclusions These results represented the first evidence of preserved HRS, assessed by γH2AX- and 53BP1-labelled DSB foci, throughout a 7-week treatment course with daily repeated subtherapeutic dose fractions. |
| Databáze: | OpenAIRE |
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