Cell Kinetic Characteristics In Different Parts of Multicellular Spheroids of Human Origin

Abstract

The growth fraction, the cell cycle time and the duration of the individual cell cycle phases were determined as a function of distance from the surface of multicellular spheroids of the human [uterine cervical carcinoma] cell line NHIK 3025. The techniques employed were percentage of labeled mitoses and labeling index measurements after autoradiography and flow cytometric measurements of DNA histograms. To separate cell populations from the different parts of the spheroid, fractionated trypsinization was employed. The results were compared with corresponding values in NHIK 3025 cell populations grown as monolayer cultures. While practically all cells in exponentially growing monolayer populations were proliferating, the growth fraction was between 0.6 and 0.7 in the outer parts of the spheroid. The inner region was mainly occupied by a necrotic mass. The proliferating fraction of the recognizable cells in the inner region was slightly below 0.5. The mean cell cycle time of NHIK 3025 cells in monolayer culture is 18 h. The mean cell cycle time of proliferating cells in the periphery of the spheroid was 30 h, compared to 41 h in the inner region (150 .mu.m from the spheroid surface). All phases of the cell cycle were prolonged compared to populations of exponentially growing monolayer cells. Within each part of the spheroid the distribution of cell cycle times was considerably broadened compared with monolayer populations.