BACKGROUND AND PURPOSE: Prolonged vinblastine (VLB) infusion and irradiation (IR) lead to favourable results in certain tumours types; however the underlying biological mechanisms of interaction are not well known. The aim of our study was to evaluate the dose- and time-dependent interactions between split-dose VLB treatment (mimicking prolonged infusion) and IR of sarcoma SA-1 tumours in A/J mice. METHODS: Antitumor effectiveness of different VLB-IR schedules was determined by a tumour growth delay assay, the VLB amount in the tumours by liquid chromatography coupled to mass spectrometry and DNA cell cycle analysis. RESULTS: A positive antitumor effect was obtained when tumours were irradiated immediately after the first (0 h) or second (4 h) injection of VLB treatment, despite the lower amount of VLB in the tumours as well as decreased number of cells in the IR-sensitive G2M phase at these times points as opposed to the second half of VLB split-dose scheduling. CONCLUSION: Preferential binding of VLB to microtubules (with consequent lack of available VLB to bind to DNA where it acts as a radioprotector) and the absence of radiobiologically relevant hypoxia are presumably leading to the observed therapeutic benefit of applying IR at the beginning of the prolonged VLB infusion.
BACKGROUND AND PURPOSE: Prolonged vinblastine (VLB) infusion and irradiation (IR) lead to favourable results in certain tumours types; however the underlying biological mechanisms of interaction are not well known. The aim of our study was to evaluate the dose- and time-dependent interactions between split-dose VLB treatment (mimicking prolonged infusion) and IR of sarcoma SA-1 tumours in A/J mice. METHODS: Antitumor effectiveness of different VLB-IR schedules was determined by a tumour growth delay assay, the VLB amount in the tumours by liquid chromatography coupled to mass spectrometry and DNA cell cycle analysis. RESULTS: A positive antitumor effect was obtained when tumours were irradiated immediately after the first (0 h) or second (4 h) injection of VLB treatment, despite the lower amount of VLB in the tumours as well as decreased number of cells in the IR-sensitive G2M phase at these times points as opposed to the second half of VLB split-dose scheduling. CONCLUSION: Preferential binding of VLB to microtubules (with consequent lack of available VLB to bind to DNA where it acts as a radioprotector) and the absence of radiobiologically relevant hypoxia are presumably leading to the observed therapeutic benefit of applying IR at the beginning of the prolonged VLB infusion.
Authors: G Sersa; M Krzic; M Sentjurc; T Ivanusa; K Beravs; M Cemazar; M Auersperg; H M Swartz Journal: Cancer Res Date: 2001-05-15 Impact factor: 12.701