RADIATION SENSITIVITY MODIFICATION BY CHEMOTHERAPEUTIC-AGENTS

Abstract

Three chemotherapeutic agents, chlorambucil, mustargen and BCNU[1,3-bis(2-chloroethyl)-1-nitrosourea]-409962, investigated for their possible clinical use in conjunction with radiation therapy to dramatically affect the characteristics of standard radiation survival curves (in [Chinese hamster lung fibroblasts] V79 cells and spheroids) in vitro. The agent mustargen, at a concentration of 0.25 .mu.g/ml administered 1 h prior to 9-MeV-electron exposure, had a significant effect in reducing D0 [mean lethal dose]. The 165-rad D0 observed in control curves was reduced to 105 rads in the presence of the drug. One hour preincubation with BCNU (prior to radiation exposure) at a concentration of 3.0 .mu.g/ml dramatically reduced the initial shoulder region with number values for drug curves .apprx. 1/2 of those for controls. No effect occurred when chlorambucil was combined with radiation in exponential or confluent cultures, but an enhancement ratio of 1.8 occurred when intact spheroids were pretreated with this drug.