Modification of radiation responses of murine tumors by misonidazole (Ro 07-0582), host immune capability, and Corynebacterium parvum

Abstract

The hypoxic cell sensitizer misonidazole (Ro 07-0582),1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol, significantly enhanced the local control of the weakly immunogenic C3H mouse mammary carcinoma MDAH-MCa-4 (8-mm diameter) by single doses of radiation. The dose modification factor (DMF) was 2.33 when the drug was given ip to inbred C3Hf/Bu mice in a dose of 1 mg/g body weight 30 minutes before irradiation of the tumor. The DMF in a highly immunogenic 3-methylcholanthrene-induced C3H fibrosarcoma (FSa) was 1.65 in normal mice and 1.86 in mice immunosuppressed by 600 rads whole-body irradiation 1 day before tumor transplantation. In mice treated iv with 0.25 mg Corynebacterium parvum when tumors were 6 mm in diameter and irradiated at 8 mm, local control of FSa was enhanced at low doses of radiation but was similar to that in normal mice at higher doses. In mice treated with both misonidazole and C. parvum, local control at lower doses of radiation was similar to that in mice treated with C. parvum alone but was enhanced at higher doses in mice that failed to respond to C. parvum. Cytotoxicity of misonidazole, as reflected in tumor growth, was not detected.