Radiosensitization of E. coli B/r by the cytotoxic agent procarbazine: A hypoxic cell sensitizer preferentially toxic to aerobic cells and easily oxidized

Abstract

Procarbazine has been shown to be a hypoxic cell sensitizer of moderate ability in E. coli B/r, with an achievable enhancement ratio of 1.4 at subtoxic concentrations. The drug appears to act in a manner similar to the expected with the electron-affinic radiosensitizers. However, procarbazine and the electron-affinic sensitizers differ in two important respects. Unlike the electron-affinic sensitizers, procarbazine is not easily reduced, but is easily oxidized. It is more toxic to aerobic than to hypoxic cells. At the drug dosages in present clinical use, procarbazine is likely to be only a weak radiosensitizer. The possible implications of the data for the further development of a new class of sensitizers and combination therapy are discussed.