Circadian rhythm of cell division.

The existence of circadian oscillations in the level of hormones, in numerous physiological parameters, in toxicity and in behavior is now fully recognized in all living organisms. In contrast, the synchronisation and regulation of cell proliferation by circadian rhythms in vivo is only starting to be appreciated. This article reviews the experimental evidence for circadian synchronisation of cell division in different mammalian tissues (mainly the gastro-intestinal tract and hemapoietic system), including tumoral tissues. The possible causes of this coupling of the cell cycle phases to the circadian rhythm are discussed. Testing of novel antitumour agents using murine models should take into consideration the temporal difference between murine and human circadian control of proliferation (the peak of DNA synthesis occurs during the activity period, i.e. during daytime in man, and at night-time in mice and rats). Experimental and clinical data clearly support the important implications of the circadian control of the cell cycle in the optimisation of cancer chemotherapy, both for reducing toxicity and increasing the antitumour effects.