title: 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(-(alphaD + betaD2)]] 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 alpha-parameter (factor 2.0-5.7), without altering the beta-parameter. In RKO cells sensitization with BrdUrd increased both a (factor 1.4) and beta (factor 1.3) while HT only influenced beta (factor 2.1-4.0). The combination did not further increase the a and beta. The results indicate that BrdUrd has its main effect on the parameter alpha, dominant at clinically relevant radiation doses but that HT can affect both a and beta. The addition of BrdUrd and HT provides a method to enhance the efficacy of radiotherapy.
authors.affiliation: Department of Radiotherapy, Academic Medical Center, University of Amsterdam, The Netherlands. N.A.Franken@amc.uva.nl
authors.forename: N A
authors.initials: NA
authors.lastname: Franken
authors.forename: C
authors.initials: C
authors.lastname: Van Bree
authors.forename: M A
authors.initials: MA
authors.lastname: Veltmaat
authors.forename: H M
authors.initials: HM
authors.lastname: Rodermond
authors.forename: J
authors.initials: J
authors.lastname: Haveman
authors.forename: G W
authors.initials: GW
authors.lastname: Barendsen
mesh_terms: D001973:Bromodeoxyuridine / Q000494:pharmacology*; D016923:Cell Death; D006358:Hot Temperature; D006801:Humans; D011836:Radiation Tolerance / Q000187:drug effects / Q000502:physiology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D011838:Radiation-Sensitizing Agents; D001973:Bromodeoxyuridine