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(American Journal of Pathology. 1999;154:613-622.)
© 1999 American Society for Investigative Pathology


Regular Articles

Circadian Variation in the Expression of Cell-Cycle Proteins in Human Oral Epithelium

Georg A. Bjarnason*{dagger} , Richard C. K. Jordan*{ddagger}§ and Robert B. Sothern¶

From the Toronto-Sunnybrook Regional Cancer Centre,* the Department of Medicine,{dagger} University of Toronto, the Department of Oral Pathology,{ddagger} Faculty of Dentistry, University of Toronto, the Departments of Laboratory Medicine & Dentistry,§ Sunnybrook Health Science Centre, Toronto, Canada, and the College of Biological Sciences,¶ University of Minnesota, St. Paul, Minnesota

At the tissue level, there is experimental and clinical data to suggest a cytokinetic coordination of the cell cycle with a greater proportion of cycling cells entering S-phase and mitosis at specific times of the day. The association of certain cell-cycle proteins with defined events in the cell cycle is well established and may be used to study the timing of cell-cycle phases over 24 hours. In this study oral mucosal biopsies were obtained from six normal human volunteers at 4-hour intervals, six times over 24 hours. Using immunohistochemistry, the number of positive cells expressing the proteins p53, cyclin-E, cyclin-A, cyclin-B1, and Ki-67 was determined for each biopsy and expressed as the number of positive cells per mm of basement membrane. We found a statistically significant circadian variation in the nuclear expression of all of these proteins with the high point of expression for p53 at 10:56 hours, cyclin-E at 14:59 hours, cyclin-A at 16:09 hours, cyclin-B1 at 21:13 hours, and Ki-67 at 02:50 hours. The circadian variation in the nuclear expression of cyclins-E (G1/S phase), -A (G2-phase), and -B1 (M-phase) with a normal physiological progression over time suggests a statistically significant circadian variation in oral epithelial cell proliferation. The finding of a circadian variation in the nuclear expression of p53 protein corresponding to late G1 is novel. This information has clinical implications regarding the timing of chemotherapy and radiotherapy.





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