TY  - JOUR
A1  - Djuzenova, Cholpon S.
A1  - Elsner, Ines
A1  - Katzer, Astrid
A1  - Worschech, Eike
A1  - Distel, Luitpold V.
A1  - Flentje, Michael
A1  - Polat, Bülent
T1  - Radiosensitivity in breast cancer assessed by the histone γ-H2AX and 53BP1 foci
JF  - Radiation Oncology
N2  - 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.
KW  - DNA damage
KW  - DNA repair
KW  - Peripheral blood lymphocytes
KW  - Radiosensitivity
KW  - DNS-Schädigung
KW  - DNS-Reparatur
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96110
UR  - http://www.ro-journal.com/content/8/1/98
ER  -