Document Detail


Evaluation of different biomarkers to predict individual radiosensitivity in an inter-laboratory comparison--lessons for future studies.
MedLine Citation:
PMID:  23110060     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Radiotherapy is a powerful cure for several types of solid tumours, but its application is often limited because of severe side effects in individual patients. With the aim to find biomarkers capable of predicting normal tissue side reactions we analysed the radiation responses of cells from individual head and neck tumour and breast cancer patients of different clinical radiosensitivity in a multicentric study. Multiple parameters of cellular radiosensitivity were analysed in coded samples of peripheral blood lymphocytes (PBLs) and derived lymphoblastoid cell lines (LCLs) from 15 clinical radio-hypersensitive tumour patients and compared to age- and sex-matched non-radiosensitive patient controls and 15 lymphoblastoid cell lines from age- and sex- matched healthy controls of the KORA study. Experimental parameters included ionizing radiation (IR)-induced cell death (AnnexinV), induction and repair of DNA strand breaks (Comet assay), induction of yH2AX foci (as a result of DNA double strand breaks), and whole genome expression analyses. Considerable inter-individual differences in IR-induced DNA strand breaks and their repair and/or cell death could be detected in primary and immortalised cells with the applied assays. The group of clinically radiosensitive patients was not unequivocally distinguishable from normal responding patients nor were individual overreacting patients in the test system unambiguously identified by two different laboratories. Thus, the in vitro test systems investigated here seem not to be appropriate for a general prediction of clinical reactions during or after radiotherapy due to the experimental variability compared to the small effect of radiation sensitivity. Genome-wide expression analysis however revealed a set of 67 marker genes which were differentially induced 6 h after in vitro-irradiation in lymphocytes from radio-hypersensitive and non-radiosensitive patients. These results warrant future validation in larger cohorts in order to determine parameters potentially predictive for clinical radiosensitivity.
Authors:
Burkhard Greve; Tobias Bölling; Susanne Amler; Ute Rössler; Maria Gomolka; Claudia Mayer; Odilia Popanda; Kristin Dreffke; Astrid Rickinger; Eberhard Fritz; Friederike Eckardt-Schupp; Christina Sauerland; Herbert Braselmann; Wiebke Sauter; Thomas Illig; Dorothea Riesenbeck; Stefan Könemann; Normann Willich; Simone Mörtl; Hans Theodor Eich; Peter Schmezer
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-23
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-10-30     Completed Date:  2013-04-17     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e47185     Citation Subset:  IM    
Affiliation:
Department of Radiotherapy, University Hospital of Muenster, Muenster, Germany. greveb@uni-muenster.de
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MeSH Terms
Descriptor/Qualifier:
Biological Markers / analysis*
Cells, Cultured
Comet Assay
DNA Damage / physiology
Dose-Response Relationship, Radiation
Histones / metabolism
Humans
Lymphocytes / metabolism,  radiation effects
Radiation Tolerance / physiology*
Radiation, Ionizing
Chemical
Reg. No./Substance:
0/Biological Markers; 0/H2AFX protein, human; 0/Histones
Comments/Corrections

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