Radiation sensitivity modification by chemotherapeutic agents.

Three chemotherapeutic agents, chlorambucil, mustargen, and BCNU-409962, being investigated for their possible clinical use in conjunction with radiation therapy have been shown in vitro to dramatically affect the characteristics of standard radiation survival curves (in V79 cells and spheroids). The agent mustargen, at a concentration of 0.25 microgram/ml administered 1 hour prior to 9-MeV-electron exposure, had a significant effect in reducing D0. The 165-rad D0 observed in control curves was reduced to 105 rads in the presence of drug. One hour preincubation with BCNU (prior to radiation exposure) at a concentration of 3.0 microgram/ml was found to dramatically reduce the initial shoulder region with n number values for drug curves approximately one-half those seen for controls. No effect is seen when chlorambucil is combined with radiation in exponential or confluent cultures but an enhancement ratio of 1.8 is found when intact spheroids are pretreated with this drug.