Flow Cytometric Measurement of Intracellular pH: A Dosimetric Approach to Metabolic Heterogeneity

Abstract

Cell heterogeneity may be expressed in many ways such as variability in morphology, genetics, growth rate, cell cycle distribution, membrane antigen expression, clonogeni-city, metabolic and biochemical activity, and therapeutic sensitivity. Virtually all forms of functional heterogeneity must ultimately be expressed as some difference in biochemical, metabolic or physiological patterns of activity. Not surprisingly, this may be clinically significant since growth rate, for example, can influence drug sensitivity [1]. However, quantifying metaboUc heterogeneity in tumour cells, and assessing its significance in a dosimetric sense, requires the capability either to measure the relevant biochemical pathways in each cell or to find a suitable measurement from which differences may be inferred. Since the precise pattern of metabolic activity that determines sensitivity or resistance to cytotoxic therapy is largely unknown, and since biochemical techniques preclude measurements on individual cells, a flow cytometric approach is indicated.