Molecular biomarkers of cellular and clinical radiosensitivity - 3605S04467
urn:nbn:de:0221-2009042384 BfS-RESFOR-14/09
Summary
Within the framework of this project, the clinical reaction in response to radiotherapy was compared with several cellular biomarkers in 15 matched sample pairs (radiosensitive and normal reacting radiotherapy patients). Using standardised assay protocols, different molecular parameters were compared in patients’ primary cells and thereof generated immortalised cell lines by five research groups in a ring study. Considerable interindividual differences in radiation-induced DNA repair and apoptosis could be detected with the applied test systems. The cell lines significantly differed from the primary cells in all investigated endpoints. Thus, their suitability as surrogate for primary cells in mechanistical studies on clinical radiosensitivity is rather limited.
The comparison of in vitro results with clinical data showed correlations in individual investigations. None of the cellular test systems investigated here seems however appropriate for a general application to predict the clinical reaction during or after radiotherapy. On the other hand, the genome-wide expression analysis using microarrays revealed a set of roughly 70 marker genes, which showed different radiation response in lymphocytes of radiosensitive and normal reacting patients. With regard to the development of a predictive assay, these promising results from the gene expression analyses warrant validation in larger cohorts.
