Hypoxia-dependent Reduction of I -(2Nitro1 -imidazolyl)-3- methoxy-2-propanol by Chinese Hamster Ovary Cells and KHT Tumor Cells in Vitro and in Vivo1

structure of which is shown in Chart 1, appears to have the maximum potential for clinical use. In the course of studies on the mechanism of the radiation sensitization of hypoxic cells by electron-affinic nitmocom pounds, it was observed that: (a) NIMP is more toxic to hypoxic cellsthan oxygenated celhs(16, 17) and (b) preincu bation of cells with NIMP under hypoxic conditions at 37° enhances the killing of the cells by radiation (G. F. Whit more and S. Gulyas, unpublished data). To understand theseeffectsat a molecularlevel, the fateof NIMP was investigated in CHO cells and in single-cell suspensions of KHT fibrosarcoma tumor cells in vitro. The results of these studies are described in this paper and show that under hypoxic conditions a specific reduction product of NIMP is preferentially formed. When KHT tumor-bearing C3H mice were given injections of NIMPand were analyzed for prod ucts, the concentration of this reduction product was found to be higher in the tumor than in most other tissues.