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Open Access 01-12-2013 | Research

Radiosensitivity in breast cancer assessed by the histone γ-H2AX and 53BP1 foci

Authors: Cholpon S Djuzenova, Ines Elsner, Astrid Katzer, Eike Worschech, Luitpold V Distel, Michael Flentje, Bülent Polat

Published in: Radiation Oncology | Issue 1/2013

Abstract

Background

High expression of constitutive histone γ-H2AX, a sensitive marker of DNA damage, might be indicative of defective DNA repair pathway or genomic instability. 53BP1 (p53-binding protein 1) is a conserved checkpoint protein with properties of a DNA double-strand breaks sensor. This study explores the relationship between the clinical radiosensitivity of tumor patients and the expression/induction of γ-H2AX and 53BP1 in vitro.

Methods

Using immunostaining, we assessed spontaneous and radiation-induced foci of γ-H2AX and 53 BP1 in peripheral blood mononuclear cells derived from unselected breast cancer (BC) patients (n=57) undergoing radiotherapy (RT). Cells from apparently healthy donors (n=12) served as references.

Results

Non-irradiated cells from controls and unselected BC patients exhibited similar baseline levels of DNA damage assessed by γ-H2AX and 53BP1 foci. At the same time, the γ-H2AX assay of in vitro irradiated cells revealed significant differences between the control group and the group of unselected BC patients with respect to the initial (0.5 Gy, 30 min) and residual (2 Gy, 24 h post-radiation) DNA damage. The numbers of 53BP1 foci analyzed in 35 BC patients were significantly higher than in controls only in case of residual DNA damage. A weak correlation was found between residual foci of both proteins tested. In addition, cells from cancer patients with an adverse acute skin reaction (grade 3) to RT showed significantly increased radiation-induced γ-H2AX foci and their protracted disappearance compared to the group of BC patients with normal skin reaction (grade 0–1). The mean number of γ-H2AX foci after 5 clinical fractions was significantly higher than that before RT, especially in clinically radiosensitive patients.

Conclusions

The γ-H2AX assay may have potential for screening individual radiosensitivity of breast cancer patients.

Trial registration

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Title: Radiosensitivity in breast cancer assessed by the histone γ-H2AX and 53BP1 foci
Authors: Cholpon S Djuzenova
Ines Elsner
Astrid Katzer
Eike Worschech
Luitpold V Distel
Michael Flentje
Bülent Polat
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Radiation Oncology / Issue 1/2013
Electronic ISSN: 1748-717X
DOI: https://doi.org/10.1186/1748-717X-8-98

At a glance: The STEP trials

Springer Medicine

Radiosensitivity in breast cancer assessed by the histone γ-H2AX and 53BP1 foci

Abstract

Background

Methods

Results

Conclusions

Trial registration

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Trial registration

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