Circadian and infradian aspects of the cell cycle: from past to future

A review of some aspects of circadian and infradian rhythms of the cell cycle is given. The background is that the research of the last decade has given entirely new insights into the cell cycle as a dynamic process which occurs in waves. After some short historical notes on the development of methodology for study of cell kinetics, it is reviewed how the strong variability of this function was recognized from the 1960's. This again led to an increasing understanding of the rhythmic pattern of cell renewal in various tissues of the body. Conventional methods for studying cell population kinetics gave general insights into both circadian and infradian rhythms, but were hampered by several shortcomings. The techniques were time consuming, and usually one and only one parameter could be studied at a time. However, this general knowledge both had a strong impact on the understanding of cell kinetics and provided a basis for designing cancer chemotherapy. Today we are facing a new area in the study of cell population kinetics. New, rapid and automated methods for multiparameter studies of both cell kinetics and other biological properties of cell populations have given entirely new possibilities for cell kinetic research. Methods, mainly connected to analytical cytology, can discriminate subpopulations with varying kinetic properties, and also enable monitoring of cell proliferation in normal and malignant tissues of patients. Chronobiology has had a strong impact on the understanding of cell population kinetics in the body. In the light of the new developments in the fields of growth factors and their regulatory influences on the cell cycle, important and fundamental aspects of biological rhythms are now being elucidated.