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Effect of Pentoxifylline on Radiation-Induced ${\rm G}_{2}\text{-}\text{Phase}$ Delay and Radiosensitivity of Human Colon and Cervical Cancer Cells

Ye-Xiong Li, Kerstin Weber-Johnson, Lin-Quan Sun, Nicolas Paschoud, René-Olivier Mirimanoff and Philippe A. Coucke
Radiation Research
Vol. 149, No. 4 (Apr., 1998), pp. 338-342
DOI: 10.2307/3579695
Stable URL: http://www.jstor.org/stable/3579695
Page Count: 5
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Effect of Pentoxifylline on Radiation-Induced ${\rm G}_{2}\text{-}\text{Phase}$ Delay and Radiosensitivity of Human Colon and Cervical Cancer Cells
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Abstract

Cells of three adherent cell lines with mutated p53 (WiDr and C33-A) and disrupted p53 (C4-I) were used to investigate the effect of pentoxifylline (PTX) on radiation-induced ${\rm G}_{2}\text{-}\text{phase}$ block and its relationship to radiosensitivity. Postirradiation exposure to 0.25-1.0 mM PTX resulted in an increase in radiosensitivity in a concentration-dependent manner as determined by a clonogenic assay. The change in radiation sensitivity was quantified by calculating the enhancement ratio (ER) at a clinically relevant dose of 2 Gy; the ER for WiDr cells was 1.23 ± 0.03 and 1.39 ± 0.15 for 0.5 and 1.0 mM PTX, respectively. For C33-A cells, the ER ranged from 1.04 ± 0.04 to 1.99 ± 0.17 for 0.25-1.0 mM PTX, whereas for C4-I cells the values were 1.29 ± 0.04 and 1.76 ± 0.17 for 0.25 and 0.5 mM PTX. In asynchronous WiDr, C33-A and C4-I cells, flow cytometry analysis showed a dose-dependent accumulation of cells in G2/ M phase which was detectable at 6 h and peaked at 12 h after irradiation. Such a ${\rm G}_{2}/{\rm M}\text{-}\text{phase}$ block was transient at a dose of 2 Gy and persisted at 48 or 72 h after a dose of 4 or 6 Gy. At 12 h after 2 Gy, PTX significantly reduced the radiation-induced ${\rm G}_{2}/{\rm M}\text{-}\text{phase}$ block in a dose-dependent manner. After the higher doses of 4 and 6 Gy, the dose-dependent ${\rm G}_{2}\text{-}\text{phase}$ arrest was significantly alleviated at 24 h by treatment with PTX, and the kinetics of this alleviation depended on the radiation dose. The results demonstrate that human colon and cervical cancer cells characterized by a mutated or disrupted p53 (i.e. not transfected) are radiosensitized by PTX, which alleviates the postirradiation ${\rm G}_{2}/{\rm M}\text{-}\text{phase}$ block.

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