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At least 739 records · Page 41Linked to original sources
PubMed1985

Formation of proliferative tetraploid cells after treatment of diploid cells with sodium butyrate in rat 3Y1 fibroblasts.

When randomly proliferating rat 3Y1 fibroblasts were treated with sodium butyrate, more than 90% of their cells were arrested reversibly with a 2C DNA content at least 12 h before the G1/S boundary. When cells synchronized in the early S phase were treated with butyrate, approximately 70% of all cells were arrested with a 4C DNA content. The arrests in both G1 and G2 phases by the single inhibitor suggest that the two phases share a common mechanism. The ability of cells to undergo mitosis on time was quickly lost with time of arrest in the G2 phase. Upon removal of the inhibitor, the cells arrested with a 4C DNA content entered a new S phase without intervening mitosis. The tetraploid cells thus produced kept proliferating as fast as diploid cells. These results suggest that the inhibition of the normal G2 traverse is somehow responsible for the formation of the proliferative polyploid cells.

Animals↗
PubMed1986

Differential expression of T cell differentiation antigens and major histocompatibility antigens on activated T cells during the cell cycle.

In this report we have analyzed cell cycle-related fluctuations of both quantity and density of the T cell differentiation antigens, CD3 (T3), CD4 (T4) and CD8 (T8), as well as the major histocompatibility complex (MHC) antigens on the cell surface of activated T cells. Phytohemagglutinin-activated T cells cultured for 3 days with or without conditioned medium or for 10 days with conditioned medium and mixed lymphocyte culture-derived T cell clones were used for the analysis. Correlated measurements of the surface antigen quantity (immunofluorescence), DNA content (dye Hoechst 33342), and cell size (light scatter), not influenced by synchrony induction methods and cell fixation, were performed by dual-beam flow cytometry. Our results demonstrate that the T cell differentiation antigens, CD3, CD4 and CD8, and class I MHC antigens are increased in density in the G1 phase for all activated T cells tested. In contrast, class II MHC antigens are increased in density in the G2 phase of activated T cells maintained with conditioned medium. Since it is known that the T cell differentiation antigens and class I MHC antigens on activated T cells are necessary for proliferation of T cells, our study suggests that this effect is more significant in the G1 phase. The cell cycle changes in expression of class I and class II MHC antigens, but not of the T cell differentiation antigens, appear to be mediated by soluble factors, probably including interferon-gamma, which could produce a differential increase of class I and class II MHC antigens on G2 phase cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1984

Population dynamics of arterial cells. XIV. Evidence for no significant G2 arrest of intimal and medial cells in young nonatherosclerotic swine.

In an earlier study of swine results from analysis of tritiated thymidine data by an "ancestor table" method suggested a substantial arrest of arterial cells in the G2 phase of the cell cycle. A later study with a cytofluorometric method gave contradictory results with no evidence for significant G2 arrest. On reexamination of the earlier data with the ancestor table method in the light of current knowledge, it was found that the fact that nuclei in the S and G2 phases prior to division are larger than those in G1 after division had not been taken into account. The main purpose of the current study was to find out whether the evidence for G2 arrest would entirely disappear if adjustments were made for differences in nuclear sizes before and after division. A baseline group sacrificed 2 hr after tritiated thymidine injection and two experimental groups (one fed hyperlipidemic diet and the other given cholesterol-free mash) sacrificed 47 hr after injection were studied. Using the ancestor table method it was found that virtually all labeled arterial cells divided in both groups; thus there is no evidence for G2 arrest. The data was also analyzed with a form of the "mean grain count halving" method and this also showed all labeled cells dividing.

Animals↗
PubMed1993

Cytochalasin D-induced actin gene expression in murine erythroleukemia cells.

There is a dynamic equilibrium between monomeric G-actin and polymeric F-actin microfilaments (MFs) in eucaryotic cells. We have previously shown that disruption of MFs with cytochalasin D (CD) induced beta-actin gene transcription, resulting in elevated levels of beta-actin mRNA and protein synthesis. CD also inhibited cell growth by arresting progression through the S phase of the cell cycle. These CD-induced responses were reversible since recovering cells progressed through the G2 phase and resumed normal growth while beta-actin mRNA and protein synthesis rapidly returned to control levels. In the present study, we show that the response of beta- and gamma-actin genes is due to the synthesis of a protein(s) acting at a 5' regulatory element that may be independent of or require sequences in addition to the serum response element (SRE). CD induces beta- and gamma-actin mRNA in a dose-dependent manner, reaching a maximum of 20-fold over control mRNA levels at 30 microM. beta- and gamma-Actin gene expression was also induced 5-fold by serum stimulation of quiescent murine erythroleukemia (MEL) cells, while combined treatment with serum and CD had an additive effect. Two protein synthesis inhibitors, cycloheximide and puromycin, blocked the CD-induced increase in beta-actin mRNA, in contrast to the serum-induced increase which is insensitive to inhibitors of protein synthesis. The rapid return of beta-actin mRNA to basal levels following CD removal did not require protein synthesis nor did it require progression through the G2 phase of the cell cycle. A vector containing the 5' end of the beta-actin gene linked to a CAT reporter responded to CD when transfected into MEL cells, localizing the responsive element to the 5' portion of the beta-actin gene. By contrast, a minimal 99-bp actin promoter-CAT construct containing a functional SRE did not respond to CD.

Actins↗
PubMed1996

Early and late G2 arrest of cells undergoing radiation-induced apoptosis or micronucleation.

Conventional flow cytometric DNA measurements combined with the microscopic detection of cells in the late G2 phase of the cell cycle (characterized by the occurrence of paired kinetochores) enabled us to differentiate and to quantify early and late G2 cells 0-40 h after irradiation using a radioresistant (L929) and a radiosensitive (HL-60) cell line. This approach provided us with (1) a new kind of G2 arrest characteristic revealing changes in the G2 phase which can not be detected by flow cytometric DNA measurements, (2) cell line dependent differences in the radiation-induced transition through G2, accompanied by the occurrence of micronucleation and apoptosis, and (3) the characterization of apoptotic cells occurring probably during early G2 and bearing a rapidly reduced number of kinetochores in contrast to mitotic cells, suggesting processes different from those that operate in mitosis.

Animals↗
PubMed2000

[Effects of cytochalasin B upon mitosis of Physarum polycephalum].

Cytochalasin B, known as a functional inhibitor of actin, was microinjected into naturally synchronous plasmodia of Physarum polycephalum, and the mitotic behaviours of both CB-treated specimens and the control were examined with light and electron microscopy. Mitosis in the CB-treated specimens began about 20 to 60 minutes later than that of the control. It was delayed 35 minutes in the specimens treated with CB in the S phase of the cell cycle, and the delayed time was 20 minutes and 45 minutes, respectively. In the specimens treated with CB in early and middle G2 phase, the longest delay was 60 minutes found in the specimens treated in late G2 phase, indicating that mitosis was affected in Physarum polycephalum when the function of actin was inhibited by CB treatment. The CB-treated specimens and the control showed similarities in the process of mitosis and dynamic changes of nuclear structures, suggesting that the main effect of CB treatment upon mitosis may be to delay the triggering of the mitosis.

Animals↗
PubMed1989

Temozolomide induced differentiation of K562 leukemia cells is not mediated by gene hypomethylation.

Temozolomide (8-carbamoyl-3-methylimidazo[5,1d]-1,2,3,5-tetrazin-4-(3H)-one), an experimental antitumor agent which spontaneously decomposes to 5-(3,3-methyl-1-triazeno) imidazole-4-carboxamide, the active metabolite of the antineoplastic drug DTIC, causes erythroid differentiation of K562 leukemia cells. The increase in epsilon and gamma globin gene expression after temozolomide treatment does not appear to be due to drug-induced hypomethylation of the genes. In other genes containing many methylated sequences such as the proto-oncogenes c-myc and C-Ha-ras, temozolomide caused no detectable change in methylation. In contrast, in the same genes 5-aza-2'-deoxycytidine induced hypomethylation. Temozolomide caused DNA alkali-labile sites and an arrest of the cell cycle in G2 phase. Ethazolastone (its 3-ethylimidazo analogue) which does not cause differentiation of K562 produced no significant DNA damage and G2 phase blockade. DNA damage rather than hypomethylation may be responsible for induction of differentiation.

Blotting, Northern↗
PubMed1984

Modification of the radiation sensitivity of human tumour cells by a bis-benzimidazole derivative.

A comparison was made of the ability of either X-radiation or a DNA-specific ligand (the vital bis-benzimidazole dye; Hoechst 33342) to induce: cell killing, inhibition of de novo DNA synthesis, DNA strand breakage and the delay of cell division in human colon adenocarcinoma cells in vitro. Unlike radiation-induced cell killing, ligand-induced cytotoxicity appeared to be positively correlated with the extent of inhibition of de novo DNA synthesis--a feature consistent with the persistent binding of ligand molecules to nuclear DNA. Ligand-induced DNA strand-breaks disappeared slowly although ligand-treated cells retained apparently normal capacities to repair discrete radiogenic DNA strand-breaks. Pre-treatment of cells with Hoechst 33342 resulted in a dose-modifying enhancement of radiation resistance not associated with altered dosimetry for strand-break induction. However, radioresistance was accompanied by the protracted retention of cells in the G2 phase of the cell cycle. We suggest that the results provide direct evidence that the retention of cells in G2 phase is a sparing phenomenon and is triggered by the responses of chromatin domains to the presence of DNA damage. Our results have implications for the use of DNA-interactive agents in combined modalities for tumour therapy, and indicate a possible basis for the sparing of some tumour cells in dividing populations.

Adenocarcinoma↗
PubMed1977

Growth kinetics of plasma cell myeloma.

The plasma cell labeling index(ex) (LI) of 128 patients with multiple myeloma at various stages of disease was compared as a function of tumor mass load and length of treatment. No significant differences in LI were noted for patients with various degrees of tumor reduction. Patients observed during the first 3 months of treatment had significantly higher LI than did untreated patients and those studied after longer intervals. In vivo cell-cycle analysis of myeloma cells by the halving time of the grain-count method failed to establish the length of the cell cycle but defined the length of S+G2 phases as being longer than 60 hours. Similar studies conducted in vitro defined a shorter combined length of S+G2 phase. In 2 patients in whom continuous infusion with [3H] thymidine was performed, the generation time was established as 8 days. Both patients had similar initial LI (5.7 and 6.6) but different growth fractions (19 and 47%). The measured tumor mass doubling time was much longer than the calculated one, suggesting the presence of considerable intrinsic cell loss (83 and 47%). These observations were summarized by a hypothetical two-compartment model for the growth kinetics of multiple myeloma.

Bone Marrow↗
PubMed1987

Energy status in HeLa cells after treatment with an arresting anticancer drug.

The energy status of HeLa cells arrested in the G2 phase of the cell cycle by the antineoplastic agent cis-acid was compared with that of normal G2-phase-synchronized cells. The results showed that treatment with the drug has significantly decreased the adenylate pool, adenylate energy charge and phosphorylation potential.

Adenine Nucleotides↗
PubMed1976

Banding technique used for the detection of chromosomal aberrations induced by radiation and alkylating agents TEPA and epichlorohydrin.

Blood samples from two healthy donors were exposed, (1) to 200 R of X-rays in G0 and G1S phases of the cell cycle, and (2) to epichlorohydrin 10(-6) M and TEPA 10(-4) M in G0 and/or in G1S and G2 phases. Part of the cells was processed for chromosome studies conventionally and the other part by the trypsinization banding technique. Detailed chromosomal analysis showed that, after irradiation, 38.2% of aberrations in G0 and 18.7% in G1S phases escaped cytogenetic detection when the conventional technique was used. After exposures to TEPA and ECHH, 10.9% of aberrations were undectable in G0 and 3.3% in G1S and G2 phases. The distribution of chromosome breaks was non-random both after irradiation and after exposure to alkylating agents. However, it differed according to the mutagen used. Some chromosomal segments were broken significantly more frequently than the others (e.g. 9q12), some were resistant to breakage (e.g. the whole Y chromsome). The segments represented by G-negative bands were more fragile than the G-positive and G-variable segments.

Chromosome Aberrations↗
PubMed1988

Disturbance of cell proliferation by two model compounds of lipid peroxidation contradicts causative role in proliferative senescence.

Cumene hydroperoxide (Chp), a lipophilic peroxide, and hydroxy-nonenal (HNE), a breakdown product of lipid peroxides, were used as model compounds to assess the effects of lipid peroxidation upon cell proliferation. Amniotic fluid fibroblastlike (AFFL) cells and human diploid skin-derived (HDFL) cells were cultured with the two model compounds and cell proliferation was assayed via bromodeoxyuridine-Hoechst flow cytometry. At low doses Chp elicited an accumulation of cells in the S and G2 phase, while at higher doses the fraction of nonproliferating cells increased as well. Low doses of HNE caused an accumulation of cells in the G1 and G2 phase, whereas an additional increase of cells in S phase and in the nonproliferating fraction was found at an elevated concentration. A delay of onset of proliferation was obtained with both Chp and HNE. Permanent arrests in the S, G2, and G1 compartment are provoked by Chp only when Chp was applied together with serum. HNE, to the contrary, elicited a permanent arrest in the G2 and the G1 compartment even if added to quiescent cell cultures. Additionally, HNE caused a combination of a prolongation of the G1 phase of the cell cycle and an arrest in this compartment, which is reminiscent of cell differentiation. HDFL cells were much more sensitive toward Chp than were AFFL cells, but both cell types showed similar sensitivities toward HNE. We conclude that lipophilic peroxides exert toxic effects upon cell proliferation distinct from the pattern elicited by aldehydic breakdown products of lipid peroxides. The pattern of cell cycle arrest induced by Chp and HNE makes it unlikely that Chp and HNE, or related products of lipid peroxidation, are responsible for the limitation of the proliferative life span of human fibroblasts in culture.

Aldehydes↗
PubMed1986

Transcription of alpha-tubulin and histone H4 genes begins at the same point in the Physarum cell cycle.

In naturally synchronous plasmodia of Physarum polycephalum, both tubulin and histone gene transcription define periodic cell cycle-regulated events. Using a slot-blot hybridization assay and Northern blot analysis, we have demonstrated that a major peak of accumulation of both alpha-tubulin and histone H4 transcripts occurs in late G2 phase. Nuclear transcription assays indicate that both genes are transcriptionally activated at the same point in the cell cycle: mid G2 phase. While the rate of tubulin gene transcription drops sharply at the M/S-phase boundary, the rate of histone gene transcription remains high through most of S phase. We conclude that the cell cycle regulation of tubulin expression occurs primarily at the level of transcription, while histone regulation involves both transcriptional and posttranscriptional controls. It is possible that the periodic expression of both histone and tubulin genes is triggered by a common cell cycle regulatory mechanism.

Actins↗
PubMed2004

Crosstalk between elicitor-induced cell death and cell cycle regulation in tobacco BY-2 cells.

The molecular links between cell cycle control and the regulation of programmed cell death are largely unknown in plants. Here we studied the relationship between the cell cycle and elicitor-induced cell death using synchronized tobacco BY-2 cells. Flow cytometry and fluorescence microscopy of nuclear DNA, and RNA gel-blot analyses of cell cycle-related genes revealed that the proteinaceous elicitor cryptogein induced cell cycle arrest at the G1 or G2 phase before the induction of cell death. Furthermore, the patterns of cell death induction and defence-related genes were different in different phases of the cell cycle. Constitutive treatment with cryptogein induced cell cycle arrest and cell death at the G1 or G2 phase. With transient treatment for 2 h, cell cycle arrest and cell death were only induced by treatment with the elicitor during the S or G1 phase. By contrast, the elicitor-induced production of reactive oxygen species was observed during all phases of the cell cycle. These results indicate that although recognition of the elicitor signal is cell cycle-independent, the induction of cell cycle arrest and cell death depends on the phase of the cell cycle.

Aphidicolin↗
PubMed1997

Cell coupling and uncoupling in the ventricular zone of developing neocortex.

Cells within the ventricular zone (VZ) of developing neocortex are coupled together into clusters by gap junction channels. The specific role of clustering in cortical neurogenesis is unknown; however, clustering provides a means for spatially restricted local interactions between subsets of precursors and other cells within the VZ. In the present study, we have used a combination of 5-bromo-2'-deoxyuridine (BrDU) pulse labeling, intracellular biocytin labeling, and immunocytochemistry to determine when in the cell cycle VZ cells couple and uncouple from clusters and to determine what cell types within the VZ are coupled to clusters. Our results indicate that clusters contain radial glia and neural precursors but do not contain differentiating or migrating neurons. In early neurogenesis, all precursors in S and G2 phases of the cell cycle are coupled, and approximately half of the cells in G1 are coupled. In late neurogenesis, however, over half of the cells in both G1 and S phases are not coupled to VZ clusters, whereas all cells in G2 are coupled to clusters. Increased uncoupling in S phase during late neurogenesis may contribute to the greater percentage of VZ cells exiting the cell cycle at this time. Consistent with this hypothesis, we found that pharmacologically uncoupling VZ cells with octanol decreases the percentage of VZ cells that enter S phase. These results demonstrate that cell clustering in the VZ is restricted to neural precursors and radial glia, is dynamic through the cell cycle, and may play a role in regulating neurogenesis.

Animals↗
PubMed1992

The involvement of active DNA synthesis in camptothecin-induced G2 arrest: altered regulation of p34cdc2/cyclin B.

Cell cycle arrest in G2 phase is a common response to a variety of DNA-damaging agents. The coupling between DNA damage and G2 arrest was studied in synchronized HeLa cells using camptothecin, a highly specific inhibitor of topoisomerase I that damages DNA through the formation of reversible topoisomerase I-DNA cleavable complexes. Brief camptothecin treatment of early S-phase HeLa cells caused arrest at G2 phase and abolished the activation of p34cdc2 protein kinase. Both tyrosine dephosphorylation of p34cdc2 and cyclin B accumulation were altered. These cell cycle-dependent changes were not observed when DNA replication was inhibited by aphidicolin during the brief camptothecin treatment. Our results suggest that to produce G2 arrest, active DNA synthesis is required at the time of camptothecin treatment, as was previously shown for camptothecin-induced cytotoxicity. Furthermore, our results suggest that the interaction of the replication fork with DNA damage may ultimately trigger altered regulation of p34cdc2/cyclin B, leading to cell cycle arrest at the G2 phase.

Aphidicolin↗
PubMed1994

Cell cycle phase-dependent cytotoxicity of actinomycin D in HeLa cells.

The effects of brief actinomycin D treatment (0.1 microgram/ml, 0.5 h) on inhibition of cell growth and colony formation were studied in synchronized HeLa cells. Cells in late S and G2 phases were found to be maximally sensitive to inhibition of cell growth and colony formation after short exposure to actinomycin D. Cells in G1 and early S phases were less responsive to brief actinomycin D treatment, although there was a slowdown of cell growth between 24 and 48 h after removal of actinomycin D, recovery of cell growth was observed late (> 48 h) after drug removal. Cells in mitosis were maximally resistant to brief actinomycin D treatment, and continued to grow as did the control cells without drug. The effects of actinomycin D on inhibition of cell growth and colony formation were abolished by novobiocin but not by aphidicolin present during a brief actinomycin D treatment of cells at various cell cycle stages. Our results suggest that the effect of actinomycin D is cell cycle phase-dependent and may be involved in the action of topoisomerase II. Furthermore, actinomycin D at a low dose (0.1 microgram/ml, 0.5 h) induced a slight G1 block while a brief exposure to high dose actinomycin D (1.0 microgram/ml, 0.5 h) caused a slowdown in the rate of cell progression through S and G2/M phases. Similar S and G2/M phase block was seen in cells that had been briefly treated with actinomycin D (0.1 microgram/ml; 0.5 h) during late S and G2 phases.

Aphidicolin↗
PubMed2000

Induction of multinucleated cells caused by UVA exposure in different stages of the cell cycle.

Fibroblasts of the line 3T3 from swiss albino mice were exposed to ultraviolet A (UVA) irradiation. The cells were synchronized by treatment with nocodazole and mitotic shake-off, and then exposed to UVA irradiation in different stages of the cell cycle. Their photosensitivity varied through the cell cycle, being greatest in the G2 phase. UVA irradiation was found to induce the formation of multinucleated cells. Cells in the G1 phase were found to be most prone to multinucleation 15 min after UVA irradiation, while cells exposed to UVA irradiation in S and G2 phases contained the largest fractions of multinucleated cells 24 h after treatment. The present results indicate that multinucleated cells are formed by fusion of two or more cells shortly after UVA irradiation of early G1 cells, while impairment of cytokinesis is a possible explanation for the delayed formation of multinucleated cells after irradiation in S and G2.

3T3 Cells↗