EFFECTS OF MITOMYCIN-C AND PORFIROMYCIN ON EXPONENTIALLY GROWING AND PLATEAU-PHASE CULTURES

Laboratory studies and clinical trials are exploring the use of hypoxi a-directed cytotoxic agents as adjuncts to radiotherapy. Because hypox ia and the microenvironmental inadequacies associated with hypoxia in solid tumours inhibit cell proliferation, an essential requirement for the successful use of hypoxia-directed drugs in cancer therapy is tha t these drugs be toxic to quiescent tumour cells, as well as tumour ce lls progressing rapidly through the cell cycle. The experiments report ed here compared the cytotoxicities of mitomycin C and porfiromycin to exponentially growing and plateau phase cultures of EMT6 mouse mammar y tumour cells. The proliferative status of the cultures did not influ ence the cytotoxicity of mitomycin C under either aerobic or hypoxic c onditions, or the cytotoxicity of porfiromycin in air. Exponentially g rowing cultures were slightly more sensitive than plateau phase cultur es to porfiromycin in hypoxia, but the difference between the sensitiv ities of proliferating and quiescent cells was much smaller than the d ifference between aerobic and hypoxic cells. No evidence for repair of potentially lethal damage was found after treatment with porfiromycin in air or in hypoxia; this is in agreement with previous findings for mitomycin C. Mitomycin C and porfiromycin therefore exhibit the toxic ity to quiescent cells needed for effective use as hypoxia-directed dr ugs for the treatment of solid tumours.