Radiosensitization by Bromodeoxyuridine and Hyperthermia

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.