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From the Toronto-Sunnybrook Regional Cancer Centre,*
Toronto, Ontario, Canada; the Department of
Medicine
and the Faculty of
Dentistry,
University of Toronto, Toronto,
Ontario, Canada; the Departments of
Pathology
and Medical Biophysics and
Division of Cancer Biology Research,||
Sunnybrook and
Women’s College Health Sciences Centre, Toronto, Ontario, Canada; the
WJB Dorn VA Medical Center,¶
Columbia, South
Carolina; the Research Service,**
Stratton
Veterans Affairs Medical Center, Albany, New York; and the College of
Biological Sciences,
University
of Minnesota, St. Paul, Minnesota
We studied the relative RNA expression of clock genes throughout one 24-hour period in biopsies obtained from the oral mucosa and skin from eight healthy diurnally active male study participants. We found that the human clock genes hClock, hTim, hPer1, hCry1, and hBmal1 are expressed in oral mucosa and skin, with a circadian profile consistent with that found in the suprachiasmatic nuclei and the peripheral tissues of rodents. hPer1, hCry1, and hBmal1 have a rhythmic expression, peaking early in the morning, in late afternoon, and at night, respectively, whereas hClock and hTim are not rhythmic. This is the first human study to show a circadian profile of expression for all five clock genes as documented in rodents, suggesting their functional importance in man. In concurrent oral mucosa biopsies, thymidylate synthase enzyme activity, a marker for DNA synthesis, had a circadian variation with peak activity in early afternoon, coinciding with the timing of S phase in our previous study on cell-cycle timing in human oral mucosa. The major peak in hPer1 expression occurs at the same time of day as the peak in G1 phase in oral mucosa, suggesting a possible link between the circadian clock and the mammalian cell cycle.
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