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Friday 01 February 2002

Differential response of tumor cells and normal fibroblasts to fractionated combined treatment with topotecan and ionizing radiation.

By: Ohneseit PA, Wildemann A, Herskind C, Bamberg M, Rodemann HP.

Int J Radiat Biol 2002 Feb;78(2):125-32

PURPOSE: 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. MATERIALS AND 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. CONCLUSION: 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.

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