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RESEARCH PRODUCT

Changes in O2 Consumption of Multicellular Spheroids During Development of Necrosis

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description

Multicellular spheroids are spherical aggregates of cells that are supplied by diffusion of oxygen and substrates from the surrounding growth medium (Sutherland and Durand, 1976). Metabolic waste products are removed from the cells in these aggregates by diffusion into the growth medium. Cells within multicellular spheroids may be exposed to environmental conditions similar to those in tissue located between nutritive microvessels. Thus, tumor spheroids make it possible to study the impact of the tumor-specific micromilieu on cellular metabolism, cell cycle state, cellular viability or response to treatment. Factors in the microenvironment of tumor cells which may be relevant in this regard, are the oxygen tension (PO2), as well as the concentration of hydrogen ions (pH), of glucose and other nutrients, and of metabolic waste products such as lactate. The distribution of PO2-values in spheroids has been assessed by several investigators using O2-sensitive microelec-trodes (Carlsson et al., 1979; Kaufman et al., 1981; Mueller-Klieser and Sutherland, 1982a,b, 1983; Mueller-Klieser et al., 1983;Hetzel and Kaufman, 1983; Mueller-Klieser, 1984a,b).