1. ¹Department of Radiotherapy, University Hospital Essen, 45122 Essen, Germany
2. ²Institute of Medical Radiation Biology, University Hospital Essen, 45122 Essen, Germany

Correspondence: Dr A Sak, E-mail: ali.sak@uni-essen.de

Received 16 August 2004; Revised 5 January 2005; Accepted 19 January 2005.

Abstract

The aim of the present work was to study the role of Rad51-dependent homologous recombination in the radiation response of non-small-cell lung cancer (NSCLC) cell lines. A dose- and time-dependent increase in the formation of Rad51 and -H2AX foci with a maximum at about 4 and 1 h after irradiation, followed by a decrease, has been found. The relative fraction of cells with persisting Rad51 foci was 20–30% in radioresistant and 60–80% in radiosensitive cell lines. In comparison, a higher fraction of residual Dsb was evident in cell lines with nonfunctional p53. Transfection with As-Rad51 significantly downregulates radiation-induced formation of Rad51 foci and increases apoptosis, but did not influence the rejoining of DNA double-strand breaks. Interestingly, wortmannin, a well-known inhibitor of nonhomologous end-joining, also inhibits Rad51 foci formation. In general, there was no correlation between the clonogenic survival at 2 Gy and the percentage of initial Rad51 or -H2AX foci after ionising radiation (IR). The most reliable predictive factor for radiosensitivity of NSCLC cell lines was the relative fraction of Rad51 foci remaining at 24 h after IR. Although most of the Rad51 foci are co-localised with -H2AX foci, no correlation of the relative fraction of persisting -H2AX foci and SF2 is evident.