title: BrdUrd-induced radiosensitization of two human tumour cell lines at iso-levels of incorporation.
abstract: Bromodeoxyuridine (BrdUrd)-induced radiosensitization of two different tumour cell lines was compared at equal levels of thymidine replacement. Human lung carcinoma cells (SW-1573) and human colorectal carcinoma cells (RKO) were grown for 48 h in the presence of respectively 1 microM BrdUrd and 4 microM of BrdUrd in order to obtain equal levels of BrdUrd into the DNA. In SW cells the level of thymidine replacement by BrdUrd was 6.7+/-0.5% and in RKO cells this was 7.1+/-0.8. Cell survival after irradiation with single doses up to 8 Gy, was determined with clonogenic assay. The magnitude of BrdUrd-induced radiosensitization was determined by analyzing radiation-dose survival curves with the linear-quadratic formula [S(D)/S(0)=exp-(alphaD+betaD2)]. In the SW cells BrdUrd radiosensitization led to a significant increase of the linear parameter, alpha, determining the initial slope of the survival curves, by a factor of about 2. In the RKO cells BrdUrd increased the value of alpha by a factor 1.4. This suggests that repair of potentially lethal damage (PLD) is inhibited. In both cell lines the quadratic term, beta, strongly influencing the high dose region of the survival curves, was not altered by sensitization by BrdUrd. The increase of alpha is of interest for clinical applications as BrdUrd sensitizes tumour cells after low doses of radiation.
authors.affiliation: Department of Radiotherapy, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE 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: J B
authors.initials: JB
authors.lastname: Kipp
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 / Q000378:metabolism / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000532:radiotherapy; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002999:Clone Cells; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000378:metabolism / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
chemical_list: D011838:Radiation-Sensitizing Agents; D001973:Bromodeoxyuridine; D013936:Thymidine