Isobologram Analysis of X-Ray-BCNU Interactions in Vitro

Abstract
9L rat brain tumor cells were exposed for 1 h to either 1, 3, 5 or 7.5 .mu.g/ml 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), followed 15 h later with graded doses (0-20 Gy [gray]) of radiation. Isobolograms constructed for 1, 2 and 3 log cell kills showed that lethality from BCNU and from radiation was additive. The analysis was extended to lower levels of survival by constructing additive dose-response curves from the isobolograms. These curves define the additive, subadditive, supraadditive and protective regions for each survival plot. For log cell kills greater than 3, additivity of lethality was found for radiation and either 1 or 7.5 .mu.g/ml BCNU, while supraadditivity of lethality was found for radiation and either 3 or 5 .mu.g/ml BCNU. All concentrations of BCNU interacted positively with all doses of radiation to give enhanced cell kill.