Profiles of Oxygen Partial Pressure and Oxygen Consumption Inside Multicellular Spheroids

Abstract

The distribution of oxygen inside multicellular spheroids serving as a tumor model (Sutherland et al. 1971; Sutherland and Durand 1976; Yuhas et al. 1977; Haji-Karim and Carlsson 1978) is of considerable interest, since the questions as to whether lack of oxygen induces the development of necrotic zones and whether it enhances the radioresistance of the cells are still open (Thomlinson and Gray 1955; Gray 1961; Tannock 1968, Boag 1969). Assuming a cylindrical geometry and a homogeneous oxygen consumption, the investigators just cited calculated the corresponding PO₂ profiles to estimate the size of an oxygen-depleted zone. Other groups cultured multicellular spheroids and measured central PO₂ profiles within the spheroids using PO₂ microneedle electrodes to obtain more direct information about the distribution of oxygen in multicellular spheroids (Carlsson et al. 1979; Kaufmann et al. 1981; Muller-Klieser and Sutherland 1982a, b). The question of the size of an oxygen-depleted zone within a biological tissue is closely linked with the question of the balance between oxygen supply and oxygen consumption. As mentioned above, in the past oxygen consumption was usually assumed to be homogeneous throughout the viable rim of the spheroid, but this assumption seems not reasonable, since J. Carlsson (personal communication) has measured an increase of the percentage of extracellular space from the surface to the center, i.e., the density of cells decreases. Even if the turnover of cells remains constant, the mean oxygen consumption as used in theoretical models will decrease.