Journal
RADIATION ONCOLOGY
Volume 8, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1748-717X-8-98
Keywords
DNA damage; DNA repair; Peripheral blood lymphocytes; Radiosensitivity
Funding
- Deutsche Krebshilfe [109043]
- German Research Foundation (DFG)
- University of Wuerzburg
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Background: High expression of constitutive histone. gamma-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 gamma-H2AX and 53BP1 in vitro. Methods: Using immunostaining, we assessed spontaneous and radiation-induced foci of gamma-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 gamma-H2AX and 53BP1 foci. At the same time, the gamma-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 gamma-H2AX foci and their protracted disappearance compared to the group of BC patients with normal skin reaction (grade 0-1). The mean number of gamma-H2AX foci after 5 clinical fractions was significantly higher than that before RT, especially in clinically radiosensitive patients. Conclusions: The gamma-H2AX assay may have potential for screening individual radiosensitivity of breast cancer patients.
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