Circadian variation in cell division of the mouse alimentary tract, bone marrow and corneal epithelium

Scheving, Lawrence E.; Burns, E. Robert; Pauly, John E.; Tsai, T H

doi:10.1002/ar.1091910407

Cited by 141 publications

(58 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data suggest that it may be possible for the cell-cycle rhythm to be entrained to 24-h fluctuations in temperature in a rhythmic host environment. Discussion DNA synthesis, mitosis, and the expression of cell-cycle proteins in mammalian tissues (e.g., skin, bone marrow, gut, tongue, and oral mucosa) occur with a 24-h cycle in vivo (3)(4)(5)(49)(50)(51)(52)(53)(54)(55) and circadian periodicity of cell mitosis persists in rodents in constant darkness (2,5). Daily rhythms of cell-cycle protein expression (Cyclins E, A, and B1) were also observed in human oral epithelium sampled by biopsy at 4-h intervals for 24 h from healthy human subjects (3).…”

Section: Resultsmentioning

confidence: 99%

Circadian-independent cell mitosis in immortalized fibroblasts

Yeom

Pendergast

Ohmiya

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Two prominent timekeeping systems, the cell cycle, which controls cell division, and the circadian system, which controls 24-h rhythms of physiology and behavior, are found in nearly all living organisms. A distinct feature of circadian rhythms is that they are temperaturecompensated such that the period of the rhythm remains constant (∼24 h) at different ambient temperatures. Even though the speed of cell division, or growth rate, is highly temperature-dependent, the cell-mitosis rhythm is temperature-compensated. Twenty-fourhour fluctuations in cell division have also been observed in numerous species, suggesting that the circadian system is regulating the timing of cell division. We tested whether the cell-cycle rhythm was coupled to the circadian system in immortalized rat-1 fibroblasts by monitoring cell-cycle gene promoter-driven luciferase activity. We found that there was no consistent phase relationship between the circadian and cell cycles, and that the cell-cycle rhythm was not temperature-compensated in rat-1 fibroblasts. These data suggest that the circadian system does not regulate the cell-mitosis rhythm in rat-1 fibroblasts. These findings are inconsistent with numerous studies that suggest that cell mitosis is regulated by the circadian system in mammalian tissues in vivo. To account for this discrepancy, we propose two possibilities: (i) There is no direct coupling between the circadian rhythm and cell cycle but the timing of cell mitosis is synchronized with the rhythmic host environment, or (ii) coupling between the circadian rhythm and cell cycle exists in normal cells but it is disconnected in immortalized cells.O rganization of physiology and behavior into specific time domains is a fundamental property of nearly all living organisms. Anticipation of periodic changes in the environment presumably increased survival and reinforced the development of endogenous circadian oscillators (1). Because cell division is critical to the survival of unicellular organisms and the integrity of DNA is susceptible to UV irradiation, the progression of the cell cycle was probably also strongly affected by daily changes in the environment. Indeed, multiple studies have measured diurnal fluctuations in cell division such that mitosis occurs at a specific time of day in numerous species ranging from unicellular organisms (2) to humans (3-5). These data suggest that the circadian and cell cycles may be coupled in vivo.Circadian rhythms are self-sustained oscillations in physiology and behavior with endogenous periods of ≈24 h that can be synchronized, or entrained, to environmental cues such as the light/dark cycle or temperature (6). In mammals, the master circadian clock is located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. Genes that are important for circadian timekeeping are expressed not only in the SCN but also in many peripheral tissues, including fibroblasts (7-11). Immortalized embryonic fibroblasts exhibit circadian rhythms of gene expression (12) and, using singlecell imaging...

show abstract

Section: Resultsmentioning

confidence: 99%

Circadian-independent cell mitosis in immortalized fibroblasts

Yeom

Pendergast

Ohmiya

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Cellular proliferation is organized within proliferating tissues throughout each day (1)(2)(3)(4). In the usually quiescent liver, regeneration following partial hepatectomy results in tight circadian gating of cell division at specific times of day (5).…”

Section: Introductionmentioning

confidence: 99%

Circadian clock coordinates cancer cell cycle progression, thymidylate synthase, and 5-fluorouracil therapeutic index

Wood

Du-Quiton

You

et al. 2006

Molecular Cancer Therapeutics

100

101

View full text Add to dashboard Cite

Dysregulated cellular proliferation is a characteristic property of cancer. We show that, despite this fact, cancers maintain high amplitude, circadian rhythms in their growth, DNA synthesis, and mitosis. These patterns are accompanied by the daily traverse of BMAL-1 protein between the cytoplasm, where it is produced, and nucleus, where it influences timing of cancer cell proliferation. This core clock gene product gates cancer cell proliferation by coordinating clock-controlled proteins, thymidylate synthase [thymidylate synthase activity (TSA) cell DNA replication], WEE-1 (cell mitosis), and vascular endothelial growth factor (growth). 5-Fluorouracil (5-FU) -induced host bone marrow and gut toxicity and tumor shrinkage following administration at six equispaced times of day allowed determination of circadian relationships among tumor growth, relevant clock, and clock-controlled proteins and dependence of 5-FU target availability (TSA) in normal and cancer tissues and resultant 5-FU toxic-therapeutic index. The time of day (hours after lights on) of low TSA in each tissue and tumor is respectively associated with greatest toxicity to that tissue and greatest tumor shrinkage. 5-FU treatment near daily awakening results in least damage to bone marrow and gut, greatest antitumor effect, and best survival. This time of day is associated with maximum tumor nuclear BMAL-1 and total cell WEE-1 protein. The described chain of events, for the first time, links cancer cell clock proteins, cancer cell DNA synthesis, proliferation, TSA, and 5-FU toxic-therapeutic index, explaining the dependence of cancer outcome on circadian timing of 5-FU.

show abstract

“…These studies suggested an S-phase acrophase in early afternoon. Scheving et al (30) showed, in rodent gut, significant circadian variation in [3H] TdR incorporation in mucosal epithelia throughout the entire gastrointestinal tract. Although the phasing of the rhythms in different regions of the gastrointestinal tract was fairly similar, the acrophase for tongue epithelium preceded that of colonic epithelium by about 3 hours.…”

Section: Discussionmentioning

confidence: 99%

Circadian Variation of Topoisomerase II-α in Human Rectal Crypt Epithelium: Implications for Reduction of Toxicity of Chemotherapy

et al. 2002

View full text Add to dashboard Cite

Topoisomerase II-alpha is a target of common chemotherapeutic agents such as doxorubicin and etoposide, which induce DNA damage by altering the activity of this enzyme. We took rectal biopsies at 4-hour intervals over a 24-hour period (seven total) from each of 10 healthy volunteers and examined immunoperoxidase-stained coded antitopoisomerase II-alpha-stained sections. A significant circadian periodicity was seen in the number of rectal crypt epithelial cell nuclei that were stained (P ‫؍‬ .01). Mean peak staining was at 7:23 a.m. ؎ 45 minutes, and the mean rate of change (difference between peak and trough expression) was 40%. Topoisomerase II-alpha expression in rectal epithelium has a significant circadian variation similar to that of tritiated thymidine incorporation. Although direct confirmation is needed, giving topoisomerase II-targeted chemotherapeutic agents at the proper time of day might reduce their mucositis side effects.

show abstract

Circadian variation in cell division of the mouse alimentary tract, bone marrow and corneal epithelium

Cited by 141 publications

References 11 publications

Circadian-independent cell mitosis in immortalized fibroblasts

Circadian-independent cell mitosis in immortalized fibroblasts

Circadian clock coordinates cancer cell cycle progression, thymidylate synthase, and 5-fluorouracil therapeutic index

Circadian Variation of Topoisomerase II-α in Human Rectal Crypt Epithelium: Implications for Reduction of Toxicity of Chemotherapy

Contact Info

Product

Resources

About