Further evidence for the absence of a hypoxic fraction in the 9L rat tumour multicellular spheroid system.

Abstract

The 9L gliosarcoma is an N-methylnitrosourea-induced rat brain tumour that has served as a predictive model for the efficacy of various chemotherapeutic agents against human brain tumours (Barker et al, 1973). Because it is one of two known animal tumour models that has no hypoxic fraction the 9L model is of questionable value for the study of the radiobiology of hypoxic cell sensitizers (Denekamp, 1980). Radiation survival curves of the intracerebral 9L (50 mg) and larger (30–2000 mg) subcutaneous 9L rat tumours do not have the “tail” that is normally associated with the presence of a hypoxic fraction (Leith et al, 1975; Wallen et al, 1980), and radiation survival curves of 9L multicellular spheroids that vary in size from small cell clusters to large spheroids, with diameters greater than 900 μm, show no tail (Deen et al, 1980). It may be that the hypoxic tail on the radiation survival curve found for other spheroid systems is, by itself, an unreliable index of the state of spheroid cell oxygenation (Durand, 1980). More sensitive probes might be the cytotoxicity of nitroimidazoles against hypoxic cells or a dose enhancement produced by nitroimidazole radiosensitization of a hypoxic cell population. It is now generally accepted that electron-affinic radiation sensitizers can act alone as cytotoxic agents and can preferentially kill hypoxic cells in monolayer or spheroid cultures (Sridhar et al, 1976; Stratford & Gray, 1978; Sutherland et al, 1980).