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Results for “Resting Phase, Cell Cycle”

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At least 19 recordsLinked to original sources
PubMed2025

Macromolecular and cytological changes in fission yeast G0 nuclei.

When starved of nitrogen, cells of the fission yeast Schizosaccharomyces pombe enter a quiescent 'G0' state with smaller nuclei and transcriptional repression. The genomics of S. pombe G0 cells has been well studied, but much of its nuclear cell biology remains unknown. Here, we use confocal microscopy, immunoblots and electron cryotomography to investigate the cytological, biochemical and ultrastructural differences between S. pombe proliferating, G1-arrested and G0 cell nuclei, with an emphasis on the histone acetylation, RNA polymerase II fates and macromolecular complex packing. Compared to proliferating cells, G0 cells have lower levels of histone acetylation, nuclear RNA polymerase II and active transcription. The G0 nucleus has similar macromolecular crowding yet fewer chromatin-associated multi-megadalton globular complexes. Induced histone hyperacetylation during nitrogen starvation results in cells that have larger nuclei and therefore chromatin that is less compact. However, these histone-hyperacetylated cells remain transcriptionally repressed with similar nuclear crowding. Canonical nucleosomes - those that resemble the crystal structure - are rare in proliferating, G1-arrested and G0 cells. Our study therefore shows that extreme changes in nucleus physiology are possible without extreme reorganization at the macromolecular level.

Schizosaccharomyces↗
PubMed2025

Modulation of Cell Cycle Kinases by Kaposi's Sarcoma-Associated Herpesvirus.

The cell cycle is governed by kinase activity that coordinates progression through a series of regulatory checkpoints, preventing the division of damaged cells. The Kaposi's sarcoma-associated herpesvirus (KSHV) encodes multiple genes that modulate or co-opt the activity of these kinases, shaping the cellular environment to promote viral persistence. By advancing the cell cycle, KSHV facilitates latent replication and subsequent transmission of viral genomes to daughter cells, while also contributing to the establishment of multiple cancer types. Conversely, during viral lytic replication, KSHV extends the resting phase of the cell cycle to prevent cellular DNA synthesis that would otherwise compete for essential replication precursors. This review will examine the mechanisms KSHV has evolved to control the kinase activity regulating host cell cycle progression.

Herpesvirus 8, Human↗
PubMed1977

Fine-structure study of the parathyroid in the gerbil, Meriones unguiculatus.

A fine-structure study of the parathyroid proper and adjacent tissues has been performed in the gerbils. The chief cells were observed in three phases of the secretory cycle. The resting chief cells contained prominent lipid droplets, mitochondria and an atrophied Golgi apparatus in a finely granular cytoplasm. The intermediate-phase chief cells were also rich in lipid but showed an organelle assembly which is much less developed than in the actively secreting cells. The active chief cells possessed a noncisternal rough endoplasmic reticulum, located often in close proximity of the mitochondria. A prominent Golgi apparatus, numerous pro-secretory granules and lysosomes are characteristic of the active cells. The significance of these morphological variations is discussed. Large mitochondria-rich cells, akin to oxyphil cells were observed in the tissue adjacent to the parathyroid proper.

Animals↗
PubMed1979

[Recovery and cycle progression in multicell spheroids after fractionated gamma-irradiation and combined hyperthermic treatment (author's transl)].

Spheroids of V79 cells were subjected to fractionated irradiation with two doses of gamma-radiation. In addition, a two hours hyperthermic treatment at 42 degrees C immediately following the first dose was applied. Cycling and resting cells of this in-vitro tumour model were then assayed for survival as function of the fractionation interval. In parallel, changes in cycle progression between the doses were measured by means of cytofluorometry. As main proliferative effects induced by this combined radiation and heat treatment transient S-phase blocking of cycling and recruitment of resting cells were observed. The split-dose survival curve displayed considerable synergistic action of heat and radiation and a six hours delay of Elkind-recovery in both cycling and resting cells.

Animals↗
PubMed1977

[Critical reflections to the problem of timing in the synchronization therapy of human malignant tumors. Mitotic-index determination, cytophotometric and radioautographic studies (author's transl)].

Formerly (1969) we have been able to demonstrate that during a lengthy inhibition of the DNA synthesis with 5-fluoro-uracil (FU), cells assemble just before, at the outset of, and within the S-phase. By taking off the inhibition, these cells start off together for the rest of the life cycle and pass the S, G2 and M phase like a wave. By the experimental condition given, the time required for passing the S phase was rather constant for all tissues. It generally took about 8 h. The sensitivity of cells to radiation depends on the current phase of their life cycle. Normally they are highly radiosensitive during the transition from G1 to S phase and within the G2 phase. Therefore we tried to improve the effectiveness of radiotherapy by radiating the synchronized cell population in the G2 phase. In clinical treatment we give an infusion with 1 g FU in 1000 ml 5.4% Glucose for 12 h. 8--9 h after the end of the infusion radiation will be applied (Betatron, individual doses: 500 rad). This treatment will be repeated until a total dose of 5000--6000 rad. Until now nearly 300 cases of patients treated in this way have been published. The 5 year-results show only in about 60% of the patients a fast reduction of the tumor. The long term results are unsatisfactory. Beside many other points the most important reason for these clinical results might be the individual length of the S phase of the tumors which prevents that radiation can be given exactly in G2 phase in each case. With mitotic-index determination, with cytophotometric investigations and the double labelling technique (3H- and 14C-Thymidine) we therefore tried to find an answer to the following questions: 1. How long is the DNA synthesis time in the individual case of human ENT tumors? 2. Does the application of FU influence the length of the S phase? 3. Will the synchronization-degree become higher by using other methods of cell cycle inhibition? With the above mentioned experimental methods we found that the length of the S phase in human tumor spreads from about 8--16 h in the individual case. The application of FU has no influence on DNA synthesis time. By using FU the degree of synchronization is about 2.5 in according to former experimental work and that of other authors. These results will be discussed in detail as well as the conclusion we draw from our experiments: to give radiation not in G2 but in G1/S of the cell cycle. Long-term observation of the patients and further animal experiments shall demonstrate whether this technique of synchronization therapy will improve the clinical results.

Autoradiography↗
PubMed1979

Inhibition of cellular transition from G1-resting to G1-prereplicative phase by aminonucleoside of puromycin.

Human embryonic lung fibroblasts (IMR-90 and WI-38) were arrested in the G1 phase of the cell cycle by serum deprivation and high population density. Within 1 hr after the addition of medium containing fresh serum, these cells showed an increase in rRNA synthesis. The inclusion of 100 micrograms per ml aminonucleoside of puromycin (AMS) in the fresh medium eliminated the serum stimulation of rRNA synthesis and prevented the cells from making the G1-resting phase to G1-prereplicative phase transition. AMS also prevented the synthesis of HnRNA normally found within 10 hr after serum stimulation. Serum-stimulated RNA synthesis in starved, SV-40 transformed fibroblasts (WI-38-VA-13 cells) was inhibited, but not completely prevented, by AMS indicating that transformed cells may produce specific RNA's that are not AMS-sensitive and that may be responsible for the failure of transformed cells to be arrested in G1.

Animals↗
PubMed1978

Poly(A) polymerase activity during cell cycle and erythropoietic differentiation in erythroleukemic mouse spleen cells.

Poly(A) polymerase activity was studied in lysates of cultured murine erythroleukemic cells (Friend cells). Incorporation of ATP into acid-precipitable products is dependendent on the presence of Mn2+ or Mg2+ and of an RNA primer. The reaction is specific for ATP as the substrate (KM=290 290 micron, it is not inhibited by actinomycin D and only slightly interferred with by ethidium bromide. Cordycepin 5'-triphosphate and sodium pyrophosphate inhibit the enzyme activity. The chain length of the products of the reaction is dependent on the primer concentration and reaches up to 30 nucleotides. Poly(A) polymerase activity is low in resting (G1 phase) cells 75 nmol ATP incorporated/h per 10(6) cells) and increases to a level about twice as high in early S phase of the cell cycle. A possible model for regulation of enzyme activity is discussed. Polymerase activity in the early phase of erythropoietic differentiation of the cells induced by butyric acid does not show any difference in comparison to untreated controls. A decrease in enzyme activity to levels characteristic for cells in G1 phase accompanies shutdown of cell growth in the course of the ongoing differentiation. Analysis of the DNA content of the cells revealed that erythropoietic differentiation of Friend cells induced by butyric acid is characterized by arrest of the cells in G1 phase of the cell cycle. Poly(A) polymerase activity in erythroleukemic cells is thus controlled only by the phase of the cell cycle; it is not affected by changes in gene expression during erythroid differentiation.

Adenosine Triphosphate↗
PubMed1976

Kinetics of haemopoietic recovery in endotoxin-treated mice.

Kinetics of mouse spleen colony forming units were studied after intra-peritoneal injection of 1 mug/blody weight bacterial endotoxin S. typhosa. When these mice were used as unirradiated and sublethally irradiated donors, it was possible to study the effect of the endotoxin injection upon the cells. Use of the treated mice as irradiated recipients of normal cells gave information about the host effect. In treated unirradiated mice, the total nucleated cell and the CFU counts were disturbed, and 2 days later a large fraction of the CFU were found in the DNA synthesis (S) phase. This meant that injection of endotoxin generated factors affecting the kinetics of the CFU and triggering the resting CFU into the proliferative cycle. If then the mice were given supralethal irradiation and used as recipients of normal bone marrow cells, more CFU seeded to the spleen as compared to normal recipients; but the dip and the growth rate of the CFU were not changed. Hence the endotoxin-generated factors had been eliminated in 2 days. A total body sublethal irradiation by 400 rad X-ray 2 days after endotoxin injection reduced the post-irradiation dip in the recovery curve of the CFU, indicating that though the factors affecting the cell kinetics had been eliminated, the cycling CFU behaved like a growing population. During the first week, the growth rate of the CFU remained the same as in control irradiated mice. The growth rate of the spleen CFU of the endotoxin-treated mice slowed down during the second week, and their self-replicating ability was low. Fluctuations in the DNA synthesizing fraction of the spleen CFU suggested a variability in the ratio of the length of the S phase and the cell generation time.

Animals↗
PubMed1978

Stimulated DNA synthesis in frog nuclei by cytoplasmic extracts of temperature-sensitive mammalian cells.

Cytoplasmic extracts of proliferating cells stimulate DNA synthesis in isolated nuclei of Xenopus laevis liver. When tested by the same assay, cytoplasmic extracts of resting cells are completely inactive. When cytoplasmic extracts are prepared from cell cycle-specific temperature-sensitive mutants arrestd in the G1 phase of the cell cycle by the nonpermissive temperature, they also fail to stimulate DNA synthesis in frog nuclei. The results indicate that, to stimulate DNA synthesis in isolated frog nuclei, essentially all information of G1 cells must be present.

Animals↗
PubMed1977

Pulse cytophotometric investigations concerning ploidy and proliferation pattern of invasive squamous cell carcinomas of the cervix uteri.

Tumor cell suspensions from 100 biopsies of squamous cell carcinomas of the cervix uteri were investigated by impulse cytophotometry (ICP) after staining with pepsin-ethidium bromide. We estimated the ploidy pattern by comparing the ICP curves with normal diploid material. The originally linearly classified curves were transformed in a logarithmical manner. We found 48 diploid populations and 42 polyploid populations, among them 19 tetraploid tumors. In these the 4c-peak was the highest. In 10 cases there were aneuploid stem lines, mainly lying between 2c and 4c; 2 curves had a hypertetraploid pattern. Helpful for interpretation of the whole curve is the introduction of an index: the "relative mean DNA-content" (DNA). In 15 diploid tumors we found a low proliferating rate, characterized by low 4c-peaks. For interpretation of polyploid cell cycles a completed nomenclature of cell cycle phases was introduced. Comparing our material with chromosome analyses in laterature we found more polyploid, e.g. tetraploid tumors. It can be assumed that the estimation of ploidy pattern solely by DNA measurements has another meaning than by chromosome analyses. The higher ploid peaks in DNA distribution curves (e.g. ICP-karyograms) represent not only true polyploid nuclei but also nuclei which are in a blocked premitotic resting phase (G2 for 4c; G'2 for 8c and so on). The ICP is a valuable method for estimating biological pecularities of tumor cell suspensions.

Biopsy↗
PubMed1975

Employment of synchronized cells and flow microfluorometry in investigations on the JB-1 ascites tumour chalones.

In most experimental ascites tumours the growth rate decreases with increasing age and cell number. This decrease is caused by a prolongation of the cell cycle and an increasing accumulation of non-cycling cells in resting (or quiescent) G1 and G2 compartments. In cell-free ascitic fluid from the JB-1 ascites tumour in the plateau phase of growth lowmolecular-weight substances have been found which reversibly and specifically arrest JB-1 cells in G1 and G2. The present paper describes an in-vitro model for testing the effect of the humoral growth inhibitors contained in the ascitic fluid. The test system is based on synchronized JB-1 cells analysed by flow-through cytofluorometry. Addition to the synchronous cells of a ultrafiltrate (less than 50000 Daltons) of the JB-1 ascitic fluid was found to induce a complete, but temporary arrest of the cells at the G1-S border.

Animals↗
PubMed1978

Lack of a correlation between polyamine synthesis and DNA synthesis by cultured rat liver cells and fibroblasts.

Growth stimulation of either fetal rat liver cells or rat embryo fibroblasts in culture results in considerable increases in intracellular polyamine levels as cells proceed through the cell cycle. Treatment of such cell cultures with appropriate levels of two inhibitors of polyamine synthesis, namely alpha-hydrazino ornithine and methylglyoxal bis (guanylhydrazone), can essentially completely block these increases in cellular polyamine content. Under such conditions, where the elevation in intracellular polyamine content is prevented, cell cultures are nevertheless able to initiate DNA synthesis and subsequently synthesize DNA at rates comparable to untreated control cultures that have been growth-stimulated. These two cell types therefore contain sufficient polyamines when in a resting state (G1) to enable them to enter from G1 into S phase and traverse S phase at normal rates in the absense of further polyamine synthesis. The recruitment of cells into the first cell cycle, through serum stimulation of growth, therefore appears not to be mediated or regulated by the increases in intracellular levels of polyamines that occurs under these conditions. Conversely, the arrest of growth of these cell types resulting from serum deprivation is not mediated by a limitation of intracellular polyamine content.

Blood↗
PubMed1976

Characterization of a G1 inhibitor from old JB-1 ascites tumor fluid. Interaction with polyions and ion exchangers.

In most experimental ascites tumors the growth rate decreases with increasing age and cell number. This decrease is caused by a prolongation of the cell cycle and an increasing accumulation of noncycling cells in resting (or quiescent) G1 and G2 compartments. In cell-free ascitic fluid from the JB-1 ascites tumor in the plateau phase of growth, low molecular weight substances have been found which reversibly and specifically arrest JB-1 cells in G1 and G2. In order to characterize the JB-1 G1 inhibitor we have investigated the effect of ion exchangers and polyions on the activity of this inhibitor assayed in vitro by means of a partially synchronized JB-1 cell population analyzed by flow microfluorometry. The results indicate that polyanions and cation exchangers (immobilized polyanions) bind and abolish the G1-inhibitory activity. From this it is suggested that the G1 inhibitor is of a basic or polycationic nature. Since anion exchangers (immobilized polycations) are without effect on this activity it was surprising to find that polycations also neutralize the activity. The results indicate that this occurs by blocking an anionic G2-inhibitor receptor on the cell, thus preventing the polycationic G1 inhibitor from being bound to this receptor.

Animals↗
PubMed1979

Modulation of cell surface iron transferrin receptors by cellular density and state of activation.

This report describes investigations of plasma membrane transferring receptors on a variety of lymphoid cell lines and normal peripheral blood lymphocytes during activation and cell growth cycles. Transformed lymphoid cell lines have as many as 1,000 times the number of receptors found on normal resting lymphocytes. The number of iron transferrin receptors on continuous cell lines as well as normal human fibroblasts is down-regulated during the transition from log-phase growth to stationary plateau growth. When normal lymphocytes are transformed by mixed lymphocyte culture or mitogens, they rapidly express a 50-fold increase in the number of transferrin binding sites. This appearance of iron transferrin receptors anticipates nuclear changes during cell activation and subsequent mitosis of normal cells.

Cell Cycle↗
PubMed1978

A comparison of cell cycle-related changes in postmitotic and quiescent AF8 cells as measured by cytofluorometry after acridine orange staining.

AF8 cells were collected by mitotic detachment or made quiescent by serum restriction. Replated mitotic cells or serum-stimulated quiescent cells were then compared by flow cytofluorometry, when the use of acridine orange staining. Red fluorescence intensity (F greater than 600) was the same in quiescent cells and in cells immediately after mitosis. However, F greater than 600 increased very rapidly in postmitotic cells, while there was a delay in serum-stimulated quiescent cells. F greater than 600 reached a peak at 4 hr in postmitotic cells and between 16 and 19 hr in serum-stimulated quiescent cells. A similar delay in the time of entry into S phase occurred after serum stimulation of resting cell populations. The results are compatible with the hypothesis that cells after mitosis may enter a state that is different from the state of cells made quiescent by serum restriction.

Acridines↗
PubMed1979

Kinetic studies of cells in childhood leukemias.

A review of cell kinetic studies in acute childhood leukemia with a comparison of leukemic transformation of non-Hodgkin's lymphoma is presented in this paper. Leukemic cell populations have a longer cell cycle than their normal cell counterparts. The cell populations are comprised of proliferating and resting fractions and are capable of self-maintaining growth. Growth regulation is determined primarily by the size of the proliferating cell population or growth fraction. The growth fraction can vary as to site of disease, the clinical phase, following chemotherapeutic perturbation, and most importantly is related to the specific tumor cell type. Within a specific type of leukemia there is considerable variability of proliferative activity at time of diagnosis, but this variability bears no relationship to the subsequent clinical course. Those leukemias, such as the E rosette-positive form of lymphocytic leukemia characterized by rapid tumor growth and large tumor bulk, are also associated with tumor cell populations having larger growth fractions than standard lymphocytic leukemia. There is evidence for growth regulation of leukemic cell populations on systemic, regional, and, perhaps most importantly of all, intrinsic cell levels. It is this area of growth regulation for these tumor cell populations which currently needs the greatest research attention.

Acute Disease↗
PubMed1978

Macrophages, a normal component in seasonally involuting testes of the swan, Cygnus olor.

In the swan, Cygnus olor, spermatogenesis shows a pronounced seasonal cycle. During the long involution phase a transient invasion of macrophages into the seminiferous tubules regularly takes place at the height of regression prior to total rest. These macrophages are involved in the additional disposal of supernumerary and degenerating premature germ cells, at a time when the Sertoli cells are already filled with phagolysosomes.

Animals↗