The effect of radiosensitizer pretreatment on the response of the RIF-1 mouse sarcoma to cytotoxic drugs

We have studied the effect of misonidazole (MISO) or metronidazole (MET) pretreatment upon the response of the RIF-1 mouse tumor to cytotoxic drugs. The response to melphalan was unchanged and that to cyclophosphamide only marginally affected by pretreatment. For CCNU and chlorambucil, the dose modifying factors (DMFs) were 1.3 and 2.0 respectively for MISO and 1.0 and 1.4 respectively for MET. The acute LD50 of CCNU was reduced by MISO (DMF approximately 1.2) but depression of white blood cells was unchanged. For chlorambucil, modification of normal tissue response was similar to that seen in the tumor. Other radiosensitizers (Ro 07-1902, Benznidazole) were more effective than MISO in enhancing tumor response to chlorambucil. Compounds which do not contain nitro groups, and which are not electron-affinic, (imidazole, SKF 525A) can also produce the effect.