Release from the Crabtree effect by hypoxic cell radiosensitizers.

Abstract

The Crabtree effect can be observed when the O2 consumption of tumour cells or of mammalian cells grown in culture is measured in physiological medium containing glucose. The effect of 2 hypoxic cell radiosensitizers, misonidazole and NDPP, on the O2 consumption of Ehrlich ascites tumour cells was compared in media with and without glucose. A stimulatory effect on O2 consumption was found for 5--20mM misonidazole as well as for 0.5mM NDPP, both in media containing 10(-2)M glucose. Thus glucose induced a Crabtree effect in Ehrlich tumour cells, expressed as 38--45% inhibition of O2 consumption relative to that in the same medium without glucose. The stimulatory effect of misonidazole and NDPP on O2 utilization in medium with glucose undoubtedly appeared as a release from the Crabtree effect.