TY  - JOUR
A1  - Kroeber, Jana
A1  - Wenger, Barbara
A1  - Schwegler, Manuela
A1  - Daniel, Christoph
A1  - Schmidt, Manfred
A1  - Djuzenova, Cholpon S
A1  - Polat, Bülent
A1  - Flentje, Michael
A1  - Fietkau, Rainer
A1  - Distel, Luitpold V.
T1  - Distinct increased outliers among 136 rectal cancer patients assessed by \(\gamma\)H2AX
JF  - Radiation Oncology
N2  - Background: 
In recent years attention has focused on \(\gamma\)H2AX as a very sensitive double strand break indicator. It has been suggested that \(\gamma\)H2AX might be able to predict individual radiosensitivity. Our aim was to study the induction and repair of DNA double strand breaks labelled by \(\gamma\)H2AX in a large cohort. 

Methods: 
In a prospective study lymphocytes of 136 rectal cancer (RC) patients and 59 healthy individuals were ex vivo irradiated (IR) and initial DNA damage was compared to remaining DNA damage after 2 Gy and 24 hours repair time and preexisting DNA damage in unirradiated lymphocytes. Lymphocytes were immunostained with anti-\(\gamma\)H2AX antibodies and microscopic images with an extended depth of field were acquired. \(\gamma\)H2AX foci counting was performed using a semi-automatic image analysis software. 

Results: 
Distinct increased values of preexisting and remaining \(\gamma\)H2AX foci in the group of RC patients were found compared to the healthy individuals. Additionally there are clear differences within the groups and there are outliers in about 12% of the RC patients after ex vivo IR. 

Conclusions: 
The \(\gamma\)H2AX assay has the capability to identify a group of outliers which are most probably patients with increased radiosensitivity having the highest risk of suffering radiotherapy-related late sequelae.
KW  - histone H2AX
KW  - blood lymphocytes
KW  - in vivo
KW  - foci
KW  - individual radiosensitivity
KW  - rectal cancer
KW  - radiotherapy
KW  - DNA double strand breaks
KW  - phosphorylation
KW  - neck cancer
KW  - oral mucositis
KW  - DNA damage
KW  - radiosensitivity
KW  - repair
KW  - \(\gamma\)h2ax
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144085
VL  - 10
IS  - 36
ER  - 
TY  - JOUR
A1  - Djuzenova, Cholpon S.
A1  - Zimmermann, Marcus
A1  - Katzer, Astrid
A1  - Fiedler, Vanessa
A1  - Distel, Luitpold V.
A1  - Gasser, Martin
A1  - Waaga-Gasser, Anna-Maria
A1  - Flentje, Michael
A1  - Polat, Bülent
T1  - A prospective study on histone γ-H2AX and 53BP1 foci expression in rectal carcinoma patients: correlation with radiation therapy-induced outcome
JF  - BMC Cancer
N2  - Background
The prognostic value of histone γ-H2AX and 53BP1 proteins to predict the radiotherapy (RT) outcome of patients with rectal carcinoma (RC) was evaluated in a prospective study. High expression of the constitutive histone γ-H2AX is indicative of defective DNA repair pathway and/or genomic instability, whereas 53BP1 (p53-binding protein 1) is a conserved checkpoint protein with properties of a DNA double-strand breaks sensor.

Methods
Using fluorescence microscopy, we assessed spontaneous and radiation-induced foci of γ-H2AX and 53BP1 in peripheral blood mononuclear cells derived from unselected RC patients (n = 53) undergoing neoadjuvant chemo- and RT. Cells from apparently healthy donors (n = 12) served as references.

Results
The γ-H2AX assay of in vitro irradiated lymphocytes revealed significantly higher degree of DNA damage in the group of unselected RC patients with respect to the background, initial (0.5 Gy, 30 min) and residual (0.5 Gy and 2 Gy, 24 h post-radiation) damage compared to the control group. Likewise, the numbers of 53BP1 foci analyzed in the samples from 46 RC patients were significantly higher than in controls except for the background DNA damage. However, both markers were not able to predict tumor stage, gastrointestinal toxicity or tumor regression after curative RT. Interestingly, the mean baseline and induced DNA damage was found to be lower in the group of RC patients with tumor stage IV (n = 7) as compared with the stage III (n = 35). The difference, however, did not reach statistical significance, apparently, because of the limited number of patients.

Conclusions
The study shows higher expression of γ-H2AX and 53BP1 foci in rectal cancer patients compared with healthy individuals. Yet the data in vitro were not predictive in regard to the radiotherapy outcome.
KW  - radiosensitivity
KW  - peripheral blood lymphocytes
KW  - DNA repair
KW  - DNA damage
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125303
VL  - 15
IS  - 856
ER  -