ISOBOLOGRAM ANALYSIS OF X-RAY-BCNU INTERACTIONS INVITRO

9L rat brain tumor cells were exposed for 1 hr to either 1, 3, 5, or 7.5 μg/ml 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), followed 15 hr later with graded doses (0 to 20 Gy) 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, supra-additive, 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 μg/ml BCNU, while supra-additivity of lethality was found for radiation and either 3 or 5 μg/ml BCNU. Therefore, all concentrations of BCNU interacted positively with all doses of radiation to give enhanced cell kill.