Differential response of tumor cells and normal fibroblasts to fractionated combined treatment with topotecan and ionizing radiation.
OBJECTIVE
The impact of the topoisomerase-I inhibitor topotecan (Hycamtin) as a single agent or in combination with ionizing radiation on clonogenic cell survival has been evaluated in three tumor cell lines and in normal fibroblasts. Both agents have been applied in a fractionated scheme in order to assess clinically relevant conditions.


METHODS
Cell inactivation was investigated in human glioblastoma cell lines U118 and U138, lung carcinoma cell line A549 and normal fibroblasts of the skin (HSF6) and lung (CCD32) using the colony formation assay.


RESULTS
The glioblastoma cell lines were highly sensitive to the drug, whereas normal fibroblasts were much less sensitive. A significant antagonistic effect of the drug combined with irradiation was found for normal fibroblasts, while glioblastoma cells showed no evidence of interaction, indicating additivity. A549 cells showed a biphasic response to topotecan alone and in combination with irradiation, suggesting induction of resistence to the drug.


CONCLUSIONS
Differential effects of combined topotecan/radiation treatment were detected between cells of normal tissue and tumor cells, being antagonistic in fibroblasts of the skin and lung, but not in tumor tissue, especially in glioblastoma cells.
Ohneseit
P A
PA
Section of Radiobiology and Molecular Environmental Research, Department of Radiation Oncology, University of Tübingen, Röntgenweg 11, 72076 Tübingen, Germany.
Wildemann
A
A
Herskind
C
C
Bamberg
M
M
Rodemann
H P
HP
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005347:Fibroblasts / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011839:Radiation, Ionizing; D013997:Time Factors; D059004:Topoisomerase I Inhibitors; D019772:Topotecan / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D019772:Topotecan