The biological effect of pentoxifylline on the survival of human head and neck cancer cells treated with continuous low and high dose-rate irradiation

The aim of this study was to compare the radiosensitivity effect of the G2/M arrest-abrogating substance, pentoxifylline (PTX), with high dose-rate irradiation (HDRI) and low dose-rate irradiation (LDRI), during which DNA repair and cell proliferation occur. Three squamous cell carcinoma cell lines, FaDu, RPMI 2650 and SCC-61, with differences in genomic imbalance and intrinsic radiosensitivity, were irradiated with 140 cGy/min (HDRI) and 0.7 cGy/min (LDRI) in the presence and absence of 2.0 mM PTX. The surviving fraction at 2.0 Gy (SF2) and cell-cycle phase distribution were assessed by DNA flow cytometry analysis and bromodeoxyuridine incorporation. With HDRI and LDRI the SF2 of FaDu cells decreased by 38.5% and 27.6%, respectively, while the corresponding figures for RPMI 2650 were 28.5% and 48.5%, and for SCC-61 were 44.2% and 28.6%. Increases in G2 populations were evident after both HDRI and LDRI of all cell lines. The enhancement in the cytotoxic effect of PTX was statistically significant after HDRI as well as after LDRI in all three cell lines. We therefore conclude that PTX in combination with LDRI is worth further study, both in vitro, for disclosing underlying mechanisms, and in vivo, to confirm the findings.