Chronobiology of Cell Proliferation

Abstract

Traditionally, cell proliferation within mammalian tissues has been assumed to be asynchronous or random. Numerous investigators who have studied this phenomenon have ignored the potential importance of temporal, particularly circadian, variation. Within the last 20 years, however, rhythmic change in cell proliferation has been incontrovertibly demonstrated in a variety of tissues and organs. In fetal and neonatal tissues, such variation appears to be primarily ultradian (Goodrum et al. 1974), whereas in adult tissues it also has a strong circadian component for both the S and the M phases of the cell cycle (Scheving and Pauly 1967). Furthermore, the proliferative response of cells to chemical, environmental, and hormonal stimuli also has been shown to be rhythmic, and this has important clinical implications. In spite of this evidence, some investigators continue to underestimate the importance of rhythmicity (Scheving 1981; Scheving and Pauly 1974). Circadian variation in cell proliferation in a number of tissues has been reviewed earlier (Scheving and Pauly 1973). The objective of this chapter is to consider more recent work and to demonstrate how an appreciation of such rhythms is advantageous in basic research on growth and treatment of growth-related disorders, including cancer chemotherapy.