Radiosensitization in sarcoma cell lines with a p53 missense mutation correlates with prevention of irradiation G2/M arrest but not with induction of apoptosis.
We analysed the effects of caffeine and taxol on the radiobiological behaviour of two human sarcoma cell lines (RD, SK-LMS-1) each with a p53 missense mutation. Treatment with 2 mM caffeine resulted in an inhibition of the irradiation induced G2/M arrest in both cell lines. This effect was coupled with a radiosensitization in cell line SK-LMS-1 after an irradiation with 6 Gy (enhancement factor of 5.0). However, the effect of radiosensitization was not correlated with an induction of apoptosis. Incubation with 20 nM taxol increased the irradiation induced apoptosis almost 3-fold in cell line SK-LMS-1, but not in cell line RD. However, taxol had no effect on the irradiation induced G2/M arrest or radiosensitivity in either cell line. The results support the hypothesis that the prevention of irradiation induced G2/M arrest but not the induction of apoptosis plays a critical role in determining radiosensitivity in sarcoma cell lines with p53 mutations.
Bache
M
M
Department of Radiotherapy and Institute of Pathology, Martin-Luther-University of Halle-Wittenberg, D-06097 Halle/Saale, Germany. matthias.bache@medizin.uni-halle.de
Oehlmann
S
S
Meye
A
A
Bartel
F
F
Kappler
M
M
Würl
P
P
Schmidt
H
H
Rath
F W
FW
Dunst
J
J
Taubert
H
H
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D002110:Caffeine / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D016195:G2 Phase / Q000187:drug effects / Q000528:radiation effects*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008938:Mitosis / Q000187:drug effects / Q000528:radiation effects*; D020125:Mutation, Missense; D017239:Paclitaxel / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012509:Sarcoma / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects*
D010726:Phosphodiesterase Inhibitors; D011838:Radiation-Sensitizing Agents; D002110:Caffeine; D017239:Paclitaxel