Investigation of taxol as a potential radiation sensitizer

Abstract

The authors evaluated the effects of taxol, a microtubular inhibitor, as a possible radiation sensitizer on the human leukemic cell line (HL-60). Taxol acts as a mitotic inhibitor, blocking cells in the G2M-phase of the cell cycle. The differential radiation sensitivity of cells in various phases of the cell cycle has been well recognized. This study was focused on the possible interaction between radiation and a microtubular inhibitor, taxol, in regard to its ability to synchronize cells at the G2M-phase of cell cycle and, thereby, enhance the radiation sensitivity of the cells. HL-60 cells were exposed to 3 x 10(-8) M concentrations of taxol for 1 hour at 37 degrees C followed by reculturing for 24 hours in drug-free medium. The cells were then seeded into 60-mm diameter plastic dishes at appropriate cell concentrations to estimate their colony-forming efficiency. The radiation dose ranged from 0-400 cGy and was delivered in a single fraction. The cellular survival after treatment with the drug and/or radiation was determined using a soft agar clonogenic assay. When HL-60 cells were treated with taxol, up to 70% of the cells were blocked in G2M-phase, as determined by flow cytometric analysis. At the low cytotoxic dose of 3 X 10(-8) M, the sensitizing enhancement ratio was 1.48. It appears that taxol has a radiation-sensitizing effect on HL-60 cells and deserves further investigation with other cell lines.