ACTIVITY OF MITOMYCIN-C FOR AEROBIC AND HYPOXIC CELLS-INVITRO AND INVIVO

Abstract

The selective toxicity of mitomycin C was observed toward hypoxic as comapred to aerobic cells in vitro for 3 established cell ines (Chinese hamster ovary [CHO], Chinese hamster V-79 [lung fibroblast] and human HeLa [cervical carcinoma]) and for cells from the transplantable KHT murine tumor [fibro sarcoma]. The magnitude of the selective toxicity was cell line dependent. The in vivo effects were studied of mitomycin C against aerobic and hypoxic cells of 2 transplantable murine tumors: the KHT fibrosarcoma and the 16/C mammary carcinoma. Either mitomycin C was given with radiation to kill most of the aerobic cells, or it was given alone. Endpoints of response were cell survival assessed by lung colony assay for the KHT tumor, and growth delay for the 16/C tumor. In some experiments, mitomycin C appeared more effective when used with radiation than when used alone, but the results of combined treatment fell just within the range of additivity as defined by isobologram analysis. The effects of combined treatment were independent of the order in which drug and radiation were given. Mitomycin C was also used in combination with adriamycin to treat the 16/C tumor. Adriamycin spares hypoxic cells in this tumor. In 3 of 4 experiments, combined drug effects were slightly greater than predicted by an additive relationship. Mitomycin C is active against hypoxic cells in 2 murine tumors, but that it has at most minor specificity for hypoxic as compared to aerobic cells in vivo.