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Chaotic Oscillations in Cultured Cells: Rat Prostate Cancer¹

Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287

Normal prostate epithelial cells exhibit uniformity of structure, function, and DNA content. This uniformity is dramatically perturbed in cancer with the development of variance associated with tumor cell heterogeneity. The development of this kind of diversity is paralleled in models of chaotic oscillators that produce multiple pseudosteady states. We have tested prostatic cancer cells in culture for the presence of chaos by comparing the micromotion of two related rat prostate cancer cell lines that exhibited large differences in motility and metastatic potential. In these extremes of cancer cell types, our data suggest that the three criteria which characterize a chaotic oscillation are fulfilled by their cellular micromotions: (a) absence of defined regularity in the time series as evidenced using Fourier analysis and visual inspection; (b) determinism as evidenced by attractor reconstruction; and (c) sensitive dependence on initial conditions as evidenced by a positive Lyapunov exponent. Cellular motion was studied by using an electronic cell impedance sensor which records, in real time, the fluctuations in the resistive and capacitive properties of cells cultured on recording electrodes. Our data and a preliminary screen of other cell types support a model of established cell lines in culture as chaotic oscillators.

¹ This work was supported by Health and Human Services Grant NCI CA15416.

² To whom requests for reprints should be addressed, at Department of Urology, Johns Hopkins Hospital, Marburg 121, 600 North Wolfe Street, Baltimore, MD 21287.

Received 2/19/96. Accepted 6/18/96.