Diurnal Fluctuations in the Numbers of DNA Synthesizing Nuclei in Various Mouse Tissues

Pilgrim, Ch.; Erb, Walter; Maurer, W.

doi:10.1038/199863a0

Cited by 173 publications

(33 citation statements)

References 4 publications

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“…Both of these mechanisms involve an intrapulmonary pool of dividing cells that would be sensitive to the effects of radiation. Diurnal fluctuations in the synthesis ofDNA have been demonstrated in various tissues of the mouse and other species (43,44 One criticism of the present study is that although AM have been demonstrated to undergo DNA synthesis, an observation that has been confirmed by flow cytometry (8), this does not provide direct evidence of AM division. Adamson et al (6) suggested that there was no evidence of an increase in DNA synthesis by AM following phagocytosis; moreover, the presence of mitotic figures in the AM population implies that AM are capable of progression through the cell cycle.…”

Section: Discussioncontrasting

confidence: 40%

Alveolar Macrophage Kinetics after Inhalation of 239 PuO 2 by CBA/Ca Mice: Changes in Synthesis of DNA

Kellington¹,

Gibson²,

Buckle³

et al. 1992

Environmental Health Perspectives

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For wrkersin the nuclear in try, the prinry route for the entry of radioactive materials into the body is by inhalation, and the rate ofclearance of particles from the pulmonary region ofthe lung is an important factor in determining radiation dose. It is the function ofalveolar macrophages (AM) to maintain the steriity ofthe lung and to remove insoluble particles from the respiratory surfaces and airways. The AM population is not static, and under normal conditions the loss of macrophages from the alveoli via the conducting airways is balanced by renewal. Studies of the effects of external irradiation on the kinetics ofAM are numerous, but to date little is known about the effects ofinhaled radioactive particles.In this tisgation the effects ofinhaled PubO2 (plutnium diode) parti on the syntbesisof DNA by AM were studied at times up to 77 days after exposure. VW also measured the number ofcells recovered by bronchoalveolar lavage and the incidence of AM with nuclear aberrations. The latter provides a sensitive indicator of the effects of radiation.One ofthe earliest effects observed after exposure to 39PU02 isa reduction in the number of AM recovered by lavage.This reduction is associated with a 3-fold reduction in the proportion ofAM undergoing DNA synthesis at early times after exposure. The overall mean pulse labeling index of AM recovered from sham-exposed mice is 1.68%, and no trend is observed with time. At later timesafter exposure there is a concurrent increase both in the number ofAM recovered by lavage and the proportion ofAM in the S-phase ofthe celi cycle. This repopulation ofthe AM pool is associated with an increase in the incidence of AM with nuclear aberrations. The results of this study are consistent with the theory of an intrapuhmonary pool of proliferating macrophages The depletion ofthe AM pool and the latency in the induction of nuclear aberrations after exposure to 23 Pu02 can be attributed to a radiation-induced inhibition ofceil division in addition to interphase death of AM.

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Section: Discussioncontrasting

confidence: 40%

Alveolar Macrophage Kinetics after Inhalation of 239 PuO 2 by CBA/Ca Mice: Changes in Synthesis of DNA

Kellington¹,

Gibson²,

Buckle³

et al. 1992

Environmental Health Perspectives

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“…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.

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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...

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“…Each body-weight group forms a homogeneous population, with little internal variation (Table I). Presumably this reflects the constant 4 hour labelling interval we have used, as well as the uniform time of killing the animals (2 p.m.), so excluding variations due to circadian rhythms which are known to affect the nuclear cycle of other tissues (Pilgrim, Erb and Maurer, 1963 (Young and Crane, 1964) and in the kidney undergoing compensatory growth (Bury, Crane and Dutta, 1965). An exception to this depressant effect is provided by the pancreatic islet-cells for increased numbers of DNA-synthesizing nuclei are found in the hyperplastic islets of rats with steroid diabetes resulting from cortisone overdosage (Crane and Dutta, 1964).…”

Section: Discussionmentioning

confidence: 99%

Effect of age, sex, and hormonal state on tritiated thymidine uptake by rat pituitary.

Crane¹,

Loomes²

1967

Br J Cancer

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PITUITARY tumours may arise spontaneously as certain strains of female rat become old, or they may be induced in rodents by a variety of experimental methods, chiefly involving hormonal imbalance. Less is known, however, of the factors which control the magnitude of cell division and growth in the pituitary, for mitotic figures are rare and conventionally the normal gland is regarded as a stable population of cells. A more accurate assessment of normal pituitary cell growth dynamics is obtained if tritiated (3H) thymidine is used to localize by autoradiography nuclei in the DNA synthetic (S) phase of the nuclear cycle. A previous study with this technique showed that age and sex were important variables influencing 3H-thymidine labelling of the rat anterior pituitary, but these results were complicated by the fact that they were obtained from animals with various forms of experimental hypertension (Crane, Dutta and Ingle, 1965). Accordingly the experiments reported here were designed to study the influence of age, sex, the ovary and oestrus cycle, and the adrenal on the numbers of DNAsynthesizing nuclei in the rat pituitary, and to define more precisely the relationship of these factors to pituitary tumour induction. MATERIALS AND METHODSGroups of male and female albino rats of an inbred strain were used. They were fed a commercial pellet diet ad libitum and given tap water, apart from adrenalectomized rats which drank 1% saline.Bilateral adrenalectomy or oophorectomy was performed in 4 groups using a standard clean surgical technique. The rats were given a single injection of 5000 units of penicillin and 5 mg. of streptomycin after surgery and postoperative infection did not occur. ACTH (corticotrophin gel, Crookes) 10 units and hydrocortisone (hydrocortisone sodium succinate, Organon) 5 mg. were injected intramuscularly each day for 3 weeks in 2 further groups of male rats. In a further group of 30 female rats vaginal smears were examined daily for 3 weeks before killing the animals at various stages of the oestrus cycle.Tritiated thymidine (thymidine-6-T nominal, Radiochemical Centre, Amersham) was injected intraperitoneally (0.7 ,tCi/g. final body weight) at the end of each experiment. A constant 4 hour labelling time (10 a.m.-2 p.m.) was used throughout. At autopsy the relevant organs were fixed in 4% neutral formaldehyde after weighing. Autoradiographs were prepared from 5 ,u paraffin sections with stripping film from Kodak AR10 plates (Crane and Dutta, 1963). The exposure time was 6 weeks at 4°C. in dry air. The image was developed with Kodak D 19b and sections were stained through the film with 1% aqueous neutral red.

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Diurnal Fluctuations in the Numbers of DNA Synthesizing Nuclei in Various Mouse Tissues

Cited by 173 publications

References 4 publications

Alveolar Macrophage Kinetics after Inhalation of 239 PuO 2 by CBA/Ca Mice: Changes in Synthesis of DNA

Alveolar Macrophage Kinetics after Inhalation of 239 PuO 2 by CBA/Ca Mice: Changes in Synthesis of DNA

Circadian-independent cell mitosis in immortalized fibroblasts

Effect of age, sex, and hormonal state on tritiated thymidine uptake by rat pituitary.

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