## Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

## If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. 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

Ye-Xiong Li, Kerstin Weber-Johnson, Lin-Quan Sun, Nicolas Paschoud, René-Olivier Mirimanoff and Philippe A. Coucke
Vol. 149, No. 4 (Apr., 1998), pp. 338-342
DOI: 10.2307/3579695
Stable URL: http://www.jstor.org/stable/3579695
Page Count: 5
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.