Interaction of paclitaxel (Taxol (R)) and irradiation - In-vitro differences between tumor and fibroblastic cells

Aim: Optimal dose and schedule of paclitaxel in combined drug-irradiation t reatment could not be determined for most of tumors yet. The aim of this st udy was to compare in vitro cytotoxicity and radiosensitizing abilities as a function of single paclitaxel (Taxol(R)) exposure in tumor and fibroblast ic cells using different drug incubation irradiation intervals. Material and Method: A lung-carcinoma (SK-LU-I), glioblastoma (U-138 MG) an d rodent fibroblast cell line (HyB14FAF28) were used. The clonogenic assay was applied for survival investigation. alpha beta-values were calculated u sing the linear-quadratic model (log S = -alpha D - beta D-2). Cytotoxicity of Taxol(R) was examined at 0 to 50 mu M Combined Taxol(R) radiotherapy ex posure was accomplished with 10 mu M Taxol(R) plus 10 Gy irradiation (RT) f ollowing after a 1-hour and 9-hour interval. For controls cells were expose d to Cremophor EL/ethanol (CEL/eth) and a phosphate buffered saline (PBS). Results: Single Taxol(R) exposure (10 mu M) resulted in 0.54/0.50/0.84 (3-h ours incubation) and 0.094/0.48/0.82 (15-hours incubation) survival of SK-L U-1, U-138MG and HyB14FAF28 cells, respectively. Taxol(R) concentrations fr om 2 to 50 mu M only had cytotoxic effect in tumor cells. Single dose RT (1 0 Gy) led to cell survival of 0.0006/0.006/0.03. The diluent CEL/eth also s howed cytotoxic activity. Taxol(R) plus RT led to cell survival of 0.00025/ 0.0014/0.042 (1 hour) and 0.0004/0.0019/0.04 (9 hours) without significant difference between chosen lime intervals, alpha beta-values showed great va riation lacking evidence for definite radiosensitization, alpha increase af ter Taxol(R) and a decrease after CEL/eth exposure were detected. Conclusions: The data presented demonstrate a potential beneficial effect, described as co-operation, by combining Taxol(R) and RT in human tumor cell s and rodent fibroblasts. High intrinsic alpha components of the tumor cell s as well as CEL/eth's antagonizing actions could be likely to disturb and influence paclitaxel's abilities leading to radiosensitization.