Interaction of misonidazole and oxygen in the radiosensitization of mammalian cells

The radiosensitizing effect of misonidazole in the presence of various oxygen concentrations was studied using cultured Chinese hamster ovary (CHO) cells. Survival curves were measured for cells equilibrated with various combinations of oxygen and misonidazole concentrations and irradiated with 50 kVp x-rays. In cases where the two agents independently yield two moderately different enhancement ratios (ER), the combined ER is simply the higher of the two. Only when the two individual ER's are approximately equal is there some degree of increase in the overall ER. An empirical technique was derived, based on the concept of ER-equivalence and the respective K-curves of the two sensitizers, to predict the combinative effect of the agents in radiosensitization. These experimental and theoretical considerations suggest that oxygen and misonidazole share in the same sensitization mechanism and act on the same target site or sites. Since it is likely that there is a distribution of oxygen tension in a tumor sensitizing tumor cells to varying degrees, knowledge of the additive effects of misonidazole and oxygen in radiosensitization may be valuable in understanding the efficacy of the application of electron affinic drugs to cancer radiotherapy.