%0 Journal Article
%T Inhibition of homologous recombination repair with Pentoxifylline targets G2 cells generated by radiotherapy and induces major enhancements of the toxicity of cisplatin and melphalan given after irradiation
%A Lothar Bohm
%J Radiation Oncology
%D 2006
%I BioMed Central
%R 10.1186/1748-717x-1-12
%X The methylxanthine drug Pentoxifylline (TRENTAL, Sanofi-Aventis) is clinically well established for the treatment of cerebral ischemia and a variety of other vasoocclusive disorders such as intermittent claudication. [14,50]. Systemically the drug operates by enhancing the flexibility of blood cell membranes and reducing blood viscosity. The positive influence of Pentoxifylline on the microcirculation and peripheral oxygenation has led to applications in experimental radiotherapy showing small but consistent improvements of the radiotoxicity. Injection of PFX followed by irradiation 45 minutes later produces a 1.1¨C1.5 fold enhancement of tumour growth delay and this is associated with a marked reduction of tumour anoxia.[10,23,25-27,41,42,47,52].Apart from the systemic effects there is now a long list of published data indicating that Pentoxifylline (and the related drug caffeine) influences the radiobiological responses of tumour cells in an oxygen independent manner. Given to tumour cell cultures before irradiation at the subtoxic dose of 2 mM, Pentoxifylline effectively enhances radiotoxicity measured by clonogenic cell survival by factors of 1.2¨C2.0 [3,4,9,45-47].In the following I summarize our own [54] and other new in vitro data which explore the effects of this interesting drug on the damage responses of tumour cells. It is shown that Pentoxifylline emerges as an effective repair inhibitor and that this new mechanistic understanding shows great promise for application in tumour therapy.The determination of the drug toxicity enhancement factors for Melphalan, Daunorubicin and Cisplatin are based on chemosensitivity measurements using the crystal violet assay. G2/M block abrogation and measurment of cell survival under conditions of G2 block abrogation and drug addition involved control experiments measuring cell survival for irradiation alone, Pentoxifylline alone, Pentoxifylline plus irradiation, Pentoxifylline plus drug at 5 % toxicity and cytostatic drug a
%U http://www.ro-journal.com/content/1/1/12