Interaction of paclitaxel (Taxol) and irradiation. In-vitro differences between tumor and fibroblastic cells.
OBJECTIVE
Optimal dose and schedule of paclitaxel in combined drug-irradiation treatment could not be determined for most of tumors yet. The aim of this study was to compare in vitro cytotoxicity and radiosensitizing abilities as a function of single paclitaxel (Taxol) exposure in tumor and fibroblastic cells using different drug incubation irradiation intervals.


METHODS
A lung-carcinoma (SK-LU-1), glioblastoma (U-138 MG) and rodent fibroblast cell line (HyB14FAF28) were used. The clonogenic assay was applied for survival investigation. alpha beta-values were calculated using the linear-quadratic model (log S = -alpha D - beta D2). Cytotoxicity of Taxol was examined at 0 to 50 microM. Combined Taxol-radiotherapy exposure was accomplished with 10 microM Taxol plus 10 Gy irradiation (RT) following after a 1-hour and 9-hour interval. For controls cells were exposed to Cremophor EL/ethanol (CEL/eth) and a phosphate buffered saline (PBS).


RESULTS
Single Taxol exposure (10 microM) resulted in 0.54/0.50/0.84 (3-hours incubation) and 0.094/0.48/0.82 (15-hours incubation) survival of SK-LU-1, U-138 MG and HyB14FAF28 cells, respectively. Taxol concentrations from 2 to 50 microM only had cytotoxic effect in tumor cells. Single dose RT (10 Gy) led to cell survival of 0.0006/0.006/0.03. The diluent CEL/eth also showed cytotoxic activity. Taxol 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 time intervals. alpha beta-values showed great variation lacking evidence for definite radiosensitization. alpha increase after Taxol and alpha decrease after CEL/eth exposure were detected.


CONCLUSIONS
The data presented demonstrate a potential beneficial effect, described as co-operation, by combining Taxol and RT in human tumor cells and rodent fibroblasts. High intrinsic alpha components of the tumor cells as well as CEL/eth's antagonizing actions could be likely to disturb and influence paclitaxel's abilities leading to radiosensitization.
Cordes
N
N
Department of Radiation Oncology, University Hospital Erlangen-Nuernberg, Germany. Nils.Cordes@strahlen.med.uni-erlangen.de
Plasswilm
L
L
Sauer
R
R
D000230:Adenocarcinoma; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000187:drug effects* / Q000528:radiation effects*; D005434:Flow Cytometry; D005909:Glioblastoma; D006801:Humans; D008175:Lung Neoplasms; D017239:Paclitaxel / Q000008:administration & dosage*; D010315:Particle Accelerators; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D011882:Radiotherapy, High-Energy / Q000706:statistics & numerical data; D012377:Rodentia; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel