The radiosensitizing effect of Pentoxifylline at high dose rate compared to low dose rate irradiation.

A Danielsson, MSc , E Karlsson, C Mercke, MD, PhD

Department of Oncology, Goteborg University, Sweden

Aim: Experiments have been carried out to determine whether the radiosensitizing effect of the G2/M arrest abrogator substance Pentoxifylline (PTX) was more or less pronounced at high dose rate (HDR) compared to low dose rate (LDR) irradiation, during which DNA repair occurs. The importance of p53 status for radioenhancement effect was also studied. Methods: Four squamous cell carcinoma cell lines with differences in p53 status and in intrinsic radiosensitivity were irradiated with either 1.4 Gy/min (HDR) or 0.007 Gy/min (LDR) in presence or absence of 2.0 mM PTX. The clonogenic survival at 2 Gy for those groups was determined after 2 weeks in culture. Results: The surviving fraction at 2 Gy (SF2) decreased in all cell lines in the presence of PTX. In the most resistant cell line SF2 decreased from 0.5 in control group to 0.3 in the presence of PTX in both HDR and LDR irradiation groups. In the most sensitive cell line the enhancement effect of PTX was greater in the HDR group than in LDR group. Conclusions: The present study on the abrogation of G2 arrest in combination with different dose rates gives further insight into basic mechanisms governing radioresistance and radiosensitivity. At 2 Gy, a significant radio-enhancement was achieved for all investigated cell lines. This means that there is no evidence that cells with wt p53 manage to refuge in G1 arrest since the cytotoxic effect of radiation when PTX was added was seen, regardless of p53 status.

KEY WORDS: Clonogenic survival, radiosensitivity, G2/M arrest, p53.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Novel Therapies, Part 1.