Radiosensitization by bromodeoxyuridine and hyperthermia: Analysis of linear and quadratic parameters of radiation survival curves of two human tumor cell lines

Abstract

Sensitization by bromodeoxyuridine (BrdUrd) and hyperthermia (HT) on cell reproductive death induced by ionizing radiation was analyzed using the linear-quadratic [S(D)/S(0)=exp{-(αD+βD2)}] model. Plateau-phase human lung tumor cells (SW-1573) and human colorectal carcinonoma cells (RKO) were treated with BrdUrd, radiation and HT. LQ-analysis was performed at iso-incubation dose and at iso-incorporation level of BrdUrd, and at iso-HT doses and iso-survival levels after HT. Clonogenic assays were performed 24 h after treatment to allow repair of potentially lethal damage (PLD). In SW cells BrdUrd, HT or the combination significantly increased the α-parameter (factor 2.0-5.7), without altering the β-parameter. In RKO cells sensitization with BrdUrd increased both α (factor 1.4) and β (factor 1.3) while HT only influenced β (factor 2.1-4.0). The combination did not further increase the α and β. The results indicate that BrdUrd has its main effect on the parameter α, dominant at clinically relevant radiation doses but that HT can affect both α and β. The addition of BrdUrd and HT provides a method to enhance the efficacy of radiotherapy.