| Autor: |
Axel Meye, Hannelore Schmidt, J. Dunst, Peter Würl, Helge Taubert, Frank Bartel, F.W. Rath, Matthias Bache, S. Pigorsch |
| Rok vydání: |
2001 |
| Předmět: |
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| Zdroj: |
International Journal of Cancer. 96:110-117 |
| ISSN: |
0020-7136 |
| Popis: |
We have examined the modulation of radiosensitivity by using caffeine in two human sarcoma cell lines both with a p53 mutation (US8-93 and LMS6-93). In both cell lines a strong irradiation-induced G2/M arrest was coupled with a low rate of apoptosis. Incubation with caffeine resulted in a low percentage of S and G2/M cells, associated with an accumulation in G1. With a higher caffeine concentration, we detected a lower clonogenic survival with IC(50) at 2 mM. In both cell lines incubation with caffeine completely prevents the irradiation-induced G2/M arrest. This was connected to radiosensitization, but without direct correlation to an induction of apoptosis. The effect of radiosensitization rose with higher irradiation doses. However, in comparison with LMS6-93, it was stronger in cell line US8-93. A higher radiosensitization in US8-93 correlated with the prevention of strong irradiation-induced G2/M response and higher initial DNA damage. Results of Western hybridization reveal a p53-independent mechanism of radiosensitization caused by caffeine. Our findings suggest that modulation in G2/M regulation may affect a common checkpoint for tumor cells with defective p53 function. Furthermore, our results show that the enhancer effect of caffeine is dependent on a strong reduction in the number of G2/M arrested cells and on an inhibition of DNA damage repair after irradiation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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