Differential cytotoxic effects of metronidazole and other nitro-heterocyclic drugs against hypoxic tumour cells

Abstract

Drugs which have been used as radiosensitizers of hypoxic tumour cells also work directly as cytotoxic agents. Whilst aerated marnmalian cells are killed by these drugs, in vitro experiments have shown that hypoxic cells are sensitive to much lower drug concentrations. The nitroimidazole drugs metronidazole (Flagyl ®) and Ro-07-0582 and the nitrofuran, nitrofurazone, show activity in this respect. This phenomenon is affected by drug concentration, temperature and oxygen tension. In vivo experiments have shown that metronidazole and Ro-07-0582 can kill hypoxic cells in murine solid tumours, though the latter drug has only been used at very high dosages. Some of the difficulties encountered during the in vivo investigation of the specific toxicity of these drugs for hypoxic cells are discussed.