Evidence for deterministic chaos in aperiodic oscillations of proliferative activity in long-term cultured Fao hepatoma cells

The proliferative activity of long-term cultured mammalian cells exhibits t raits of a complex dynamic system, with a succession of spontaneous rises a nd falls in proliferation rate. We analyzed three successive series of prol iferation data for the Fao hepatoma cell line in longterm cultures. In the three series the proliferation rate displayed apparently disordered oscilla tions, which each lasted about 3-5 passages, with variable amplitude and we re therefore unpredictable. Such non-linear kinetics raises the major issue of whether these fluctuations are random, or determined and coordinated. W e used a graphical method of analysis of the data, which demonstrated that all troughs of proliferation were mathematically related to a common value in each series. This common value was itself related to the maximum level o f proliferation of the cell line. Non-linear analysis thus confirmed that t he fluctuations in proliferation rate of tumoral Fao cells are, at least in part, determined. This pattern evokes chaotic dynamics and is evidence for the flexible coordination of the complex system linking positive and negat ive growth regulators in long-term cultured cells.