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PubMed1983

Coordinate regulation of multiple histone mRNAs during the cell cycle in HeLa cells.

Core histone gene expression in HeLa S3 cells has been examined as a function of the cell cycle using cloned human histone gene probes. Total cellular histone mRNAs were analyzed by Northern blot analysis, and their relative abundance shown to be temporally coupled to DNA synthesis rates in S phase. The in vivo incorporation of 3H-uridine into at least fifteen heterologous histone mRNAs (in one hour pulse intervals at various times in the cell cycle), was monitored by hybrid selection. Hybridized RNAs were eluted and resolved electrophoretically to give both a quantitative and qualitative assay for multiple mRNA species. Maximal incorporation of 3H-uridine into histone mRNAs precedes their maximal accumulation, indicating that transcriptional regulation is predominant in early S phase. The turnover of histone mRNAs in late S occurs in the presence of a reduced apparent transcription rate, indicating that post-transcriptional regulation is predominant in late S. All the detected multiple histone mRNAs are coordinately regulated during the HeLa cell cycle.

Cell Cycle↗

PubMed2004

Acanthamoeba induces cell-cycle arrest in host cells.

Acanthamoeba can cause fatal granulomatous amoebic encephalitis (GAE) and eye keratitis. However, the pathogenesis and pathophysiology of these emerging diseases remain unclear. In this study, the effects of Acanthamoeba on the host cell cycle using human brain microvascular endothelial cells (HBMEC) and human corneal epithelial cells (HCEC) were determined. Two isolates of Acanthamoeba belonging to the T1 genotype (GAE isolate) and T4 genotype (keratitis isolate) were used, which showed severe cytotoxicity on HBMEC and HCEC, respectively. No tissue specificity was observed in their ability to exhibit binding to the host cells. To determine the effects of Acanthamoeba on the host cell cycle, a cell-cycle-specific gene array was used. This screened for 96 genes specific for host cell-cycle regulation. It was observed that Acanthamoeba inhibited expression of genes encoding cyclins F and G1 and cyclin-dependent kinase 6, which are proteins important for cell-cycle progression. Moreover, upregulation was observed of the expression of genes such as GADD45A and p130 Rb, associated with cell-cycle arrest, indicating cell-cycle inhibition. Next, the effect of Acanthamoeba on retinoblastoma protein (pRb) phosphorylation was determined. pRb is a potent inhibitor of G1-to-S cell-cycle progression; however, its function is inhibited upon phosphorylation, allowing progression into S phase. Western blotting revealed that Acanthamoeba abolished pRb phosphorylation leading to cell-cycle arrest at the G1-to-S transition. Taken together, these studies demonstrated for the first time that Acanthamoeba inhibits the host cell cycle at the transcriptional level, as well as by modulating pRb phosphorylation using host cell-signalling mechanisms. A complete understanding of Acanthamoeba-host cell interactions may help in developing novel strategies to treat Acanthamoeba infections.

Acanthamoeba↗

PubMed1998

Alterations in the growth factor signal transduction pathways and modulators of the cell cycle in endocervical cells from macaques exposed to TCDD.

After more than a year had elapsed since a single oral exposure to 2 and 4 microgram 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg, there was an apparent dose-related increased incidence of significant endocervical squamous metaplasia in a group of cynomolgus macaques (Scott et al., 1998). In the present experiments we investigated the mechanisms by which chemicals like TCDD could induce epithelial cell transdifferentiation in the primate endocervix. One focus of investigation was epidermal growth factor receptor (EGFR) and the key cytosolic signaling kinases, c-Src and protein tyrosine kinase (PTK), whose responses to TCDD are well characterized. A second focus was the distal kinase Erk2 that transduces the cytosolic signal into a nuclear signal, and which in combination with nuclear casein kinase II (CKII), can lead to activation of p53. Finally, we studied three key target proteins of activated p53 (wafl/p21, Cdc2 p34, and Cdk4), whose modulation could produce cell cycle effects. The studies were carried out using primary cell cultures prepared from endocervical epithelium recovered at necropsy from TCDD-treated (2 and 4 microgram TCDD/kg) and untreated macaques. There was a significant decrease in EGFR binding activity in cells from TCDD-treated animals as compared to controls. A marked increase in the protein amount of H-Ras and a significant increase in the activity of c-Src kinase, PTK, and Erk2 were found in cells from TCDD-treated animals. A significant decrease in the activity of CKII and in the protein amount of p53, wafl/p21, and Cdc2 p34 was found. On the other hand, a substantial increase in the protein amount of Cdk4 and DNA binding activity of AP-1 was found in cells from TCDD-treated animals. In vitro experiments using primary cultures of endocervical cells from untreated macaques revealed that these cells have AhR, and that c-Src protein is functionally attached to the AhR and is specifically activated upon ligand binding as judged by the following criteria. (1) A structure-activity relationship study with TCDD and three dioxin congeners revealed a rank order for their potency in activation of AhR-associated c-Src kinase from cervical cells which was identical to that of previously determined toxicity indices. (2) TCDD-induced, AhR-associated c-Src kinase activity was abolished when an AhR immunoprecipitate from cervical cells was preincubated with alpha-naphthoflavone (AhR blocker) or geldanamycin (Src kinase inhibitor) prior to the addition of TCDD. (3) The analysis of the AhR complex showed three proteins of molecular weights of 100 (AhR), 90, and 60 kDa. (4) The same protein with molecular weight 60 kDa was found when the immunoprecipitate with anti AhR-antibody was analyzed by SDS-PAGE, then transferred into nitrocellulose membrane followed by immunobloting the membrane with anti c-Src-antibody. Our data suggest that TCDD induced pathology in endocervical cells through changes in growth factor receptor signaling, other cytosolic signaling proteins, tumor suppressor proteins, and cell cycle proteins.

Animals↗

PubMed2004

Apoptosis susceptibility and cell-cycle distribution in cells from myelodysplastic syndrome patients: modulatory in-vitro effects of G-CSF and interferon-alpha.

Susceptibility to apoptosis varies in different forms of myelodysplastic syndromes (MDS). Our in vitro study aimed at better defining the cell kinetic profile by investigating whether G-CSF and interferon-alpha (IFNalpha) were capable of controling apoptotic/proliferative mechanisms in RAEB as well as in RAEB-t forms. Apoptosis and cell-cycle distribution were measured in mononuclear and in CD34+ cells from bone marrow samples of 27 MDS patients with RAEB (n = 15) and RAEB-t (n = 12). In selected samples, the in vitro influence of G-CSF and lymphoblastoid (Ly)-IFNalpha on the apoptotic susceptibility and on the cell kinetics of the above MDS populations was evaluated. RAEB samples showed a significantly greater apoptosis than RAEB-t ones, both in mononuclear cells (14.76%+/-8.73 vs. 5.95%+/-3.88, P= 0.0058) and in CD34+ cells (24.66%+/-16.08 vs. 3.96%+/-2.57, P = 0.0007). Short-term cell culture in the presence of G-CSF reduced apoptosis in CD34+ cells in all 4 RAEB samples tested (39.1%+/-40.7 vs. 21.0%+/-23.5, P = n.s.); the percentage of cells in S-phase significantly increased in 3/4 samples (19.90%+/-4.40 vs. 32.40%+/-7.85, P = 0.03). Ly-IFNalpha protected CD34+ cells from apoptosis in 3/4 RAEB samples (25.7%+/-8.06 vs. 10.9%+/-8.8, P = n.s.), but did not modulate cell-cycle distribution. G-CSF and Ly-IFNalpha failed to affect apoptosis and proliferation in RAEB-t. These observations indicate that in RAEB forms increased apoptosis can be efficiently counteracted in most of the samples by both G-CSF and Ly-IFNalpha, suggesting that only in these forms a retained regulatory mechanism on the apoptotic/ proliferative balance may allow therapeutic intervention with apoptotic regulators.

Adult↗

PubMed2000

Human immunodeficiency virus type 1 Vpr-mediated G(2) cell cycle arrest: Vpr interferes with cell cycle signaling cascades by interacting with the B subunit of serine/threonine protein phosphatase 2A.

The Vpr protein of primate lentiviruses arrests cell cycling at the G(2)/M phase through an inactivation of cyclin B-p34(cdc2) and its upstream regulator cdc25. We provide here biochemical and functional evidence demonstrating that human immunodeficiency virus type 1 (HIV-1) Vpr mediates G(2) arrest by forming a complex with protein phosphatase 2A (PP2A), an upstream regulator of cdc25. Vpr associates with PP2A through a specific interaction with the B55 regulatory subunit. This interaction is necessary but not sufficient for G(2) arrest. Interestingly, we found that Vpr association with B55-containing PP2A targets the enzymatic complex to the nucleus and, importantly, enhances the recruitment and dephosphorylation of the cdc25 substrate. Our data suggest that Vpr mediates G(2) arrest by enhancing the nuclear import of PP2A and by positively modulating its catalytic activity towards active phosphorylated nuclear cdc25.

Amino Acid Sequence↗

PubMed2000

Moderate and severe endometriosis is associated with alterations in the cell cycle of granulosa cells in patients undergoing in vitro fertilization and embryo transfer.

OBJECTIVE: To determine whether folliculogenesis is impaired in patients with endometriosis. DESIGN: Prospective study. SETTING: Yamagata University School of Medicine, Yamagata, Japan. PATIENT(S): Thirty women participating in an IVF program. INTERVENTION(S): The patients were divided into four groups according to the cause of their infertility: tubal factor (T), n = 7; male factor (M), n = 7; idiopathic (I), n = 7; and endometriosis (E), n = 9. Granulosa cells were obtained from the follicular fluid of each patient and analyzed by flow cytometry. MAIN OUTCOME MEASURE(S): The percentage of granulosa cells in each cell-cycle stage. RESULT(S): The mean (+/- SD) rate of apoptosis in the granulosa cells obtained from the patients with endometriosis was the highest among the four groups (T = 11.7% +/- 3.3%; M = 5.6% +/- 3.8%; I = 9.6% +/- 5.1%; and E = 18.6% +/- 9.6%). The percentage of S-phase granulosa cells was significantly higher in the patients with endometriosis than in all the other patients combined (E = 12.5% +/- 6%; T + M + I = 9.3% +/- 2.9%). The percentage of G2/M-phase granulosa cells was significantly lower in the endometriosis group than in the other three groups combined (E = 2.3% +/- 2.5%; T + M + I = 4.6% +/- 2.1%). CONCLUSION(S): Endometriosis impairs the cell cycle in granulosa cells. This phenomenon may have a detrimental effect on folliculogenesis.

Adult↗

PubMed1982

Calmodulin and the cell cycle: involvement in regulation of cell-cycle progression.

Calmodulin levels are elevated twofold at late G1 and/or early S phases during the growth cycle of CHO-K1 cells. These levels are maintained throughout the remainder of the cell cycle unit cytokinesis. The G1 daughter cells then contain half the intracellular calmodulin level found prior to cell division. Elevation of calmodulin at the G1-S boundary is independent of the length of G1, and the increase in calmodulin appears to be related to progression into S phase. The importance of calmodulin for G1-S progression is suggested by the ability of the anticalmodulin drug W13 to elicit specific and reversible progression delays into and through S phase.

Animals↗

PubMed1996

Normal G1/S transition and prolonged S phase within one cell cycle after seeding cells in the presence of an ornithine decarboxylase inhibitor.

We have previously found that DNA replication was affected within one cell cycle after seeding Chinese hamster ovary (CHO) cells in the presence of the polyamine biosynthesis inhibitor 2-difluoromethylornithine (DFMO). We could, however, not rule out if this was due to an effect on the G1/S transition and/or on DNA synthesis elongation. In the present paper, we use a bromodeoxyuridine- flow cytometric method to more specifically study the G1/S transition, the S phase length, and the progression of cells from S phase through G2+M and into G1, after seeding plateau phase CHO cells at low density in the absence or presence of 5 mM DFMO. We report here that DFMO-induced polyamine depletion increased the length of the S phase within one cell cycle after seeding of CHO cells in the presence of the inhibitor. No effect on the G1/S transition was observed until 2 days after seeding, suggesting that a DFMO-induced lengthening of the G1 phase occurred later than the effect on S phase progression. These results imply that the G2+M phase was not prolonged until 2 days after seeding CHO cells in the presence of DFMO.

Animals↗

PubMed1998

Cell cycle dysregulation by human cytomegalovirus: influence of the cell cycle phase at the time of infection and effects on cyclin transcription.

Human cytomegalovirus (HCMV) infection inhibits cell cycle progression and alters the expression of cyclins E, A, and B (F. M. Jault, J.-M. Jault, F. Ruchti, E. A. Fortunato, C. Clark, J. Corbeil, D. D. Richman, and D. H. Spector, J. Virol. 69:6697-6704, 1995). In this study, we examined cell cycle progression, cyclin gene expression, and early viral events when the infection was initiated at different points in the cell cycle (G0, G1, and S). In all cases, infection led to cell cycle arrest. Cells infected in G0 or G1 phase also showed a complete or partial absence, respectively, of cellular DNA synthesis at a time when DNA synthesis occurred in the corresponding mock-infected cells. In contrast, when cells were infected near or during S phase, many cells were able to pass through S phase and undergo mitosis prior to cell cycle arrest. S-phase infection also produced a delay in the appearance of the viral cytopathic effect and in the synthesis of immediate-early and early proteins. Labeling of cells with bromodeoxyuridine immediately prior to HCMV infection in S phase revealed that viral protein expression occurred primarily in cells which were not engaged in DNA synthesis at the time of infection. The viral-mediated induction of cyclin E, maintenance of cyclin-B protein levels, and inhibitory effects on the accumulation of cyclin A were not significantly affected when infection occurred during different phases of the cell cycle (G0, G1, and S). However, there was a delay in the observed inhibition of cyclin A in cells infected during S phase. This finding was in accord with the pattern of cell cycle progression and delay in viral gene expression associated with S-phase infection. Analysis of the mRNA revealed that the effects of the virus on cyclin E and cyclin A, but not on cyclin B, were primarily at the transcriptional level.

Animals↗

PubMed1985

Antigenic heterogeneity of breast cell lines detected by monoclonal antibodies and its relationship with the cell cycle.

Established cell lines were stained by immunofluorescence with four monoclonal antibodies to study the phenomenon of antigenic heterogeneity and its possible relation to the cell cycle. Five cell lines thought to be of breast origin, MCF-7, ZR-75-1, T47D, MDA-MB-231 and HBL-100, were stained with three monoclonal antibodies (LICR-LON-M8, LICR-LON-M18, LICR-LON-M24) that each stain a distinct subset of normal breast epithelial cells, i.e. demonstrate antigenic heterogeneity in normal breast epithelial cells. Contrasting monoclonal antibodies LICR-LON-FIB75 and LICR-LON-FIB86 to homogeneously expressed antigens were also used. For the antibodies demonstrating heterogeneity distinct positive and negative fractions were not seen by flow cytometry; the intensity of fluorescence varied continuously from background to a hundred times stronger than background. Fluorescent DNA staining showed no obvious relation between antigen expression and the cell cycle. The essentially constant proportion of cells of a given antigenic phenotype in the various phases suggests that these antibodies do not distinguish a phenotype associated with a distinct proliferating population of cells.

Antibodies, Monoclonal↗

PubMed1999

Molecular markers and cell cycle inhibitors show the importance of cell cycle progression in nematode-induced galls and syncytia.

Root knot and cyst nematodes induce large multinucleated cells, designated giant cells and syncytia, respectively, in plant roots. We have used molecular markers to study cell cycle progression in these specialized feeding cells. In situ hybridization with two cyclin-dependent kinases and two cyclins showed that these genes were induced very early in galls and syncytia and that the feeding cells progressed through the G2 phase. By using cell cycle blockers, DNA synthesis and progression through the G2 phase, or mitosis, were shown to be essential for gall and syncytium establishment. When mitosis was blocked, further gall development was arrested. This result demonstrates that cycles of endoreduplication or other methods of DNA amplification are insufficient to drive giant cell expansion. On the other hand, syncytium development was much less affected by a mitotic block; however, syncytium expansion was inhibited.

Animals↗

PubMed1997

Induction of cell cycle arrest and B cell terminal differentiation by CDK inhibitor p18(INK4c) and IL-6.

Cell cycle arrest and cell death are tightly coupled to terminal differentiation of B cells to plasma cells in vivo. This process was recapitulated in vitro by stimulation of IgG-bearing human B lymphoblastoid cells with interleukin-6 (IL-6), which led to orderly cell cycle arrest, differentiation, and apoptosis. In terminally differentiated plasmacytoid cells, phosphorylation of pRb was suppressed, correlating with the activation of the D-type cyclin-dependent kinase (CDK) inhibitors p18(INK4c) and p21(WAF1/CIP1). The expression of CDK6, however, remained unchanged. Activation of p18 by IL-6 was rapid, concomitant with marked enhancement of its association with CDK6 and cell cycle arrest. Overexpression of p18 in IgM-bearing lymphoblastoid cells, which differentiated in response to IL-6 but did not exit the cell cycle, reconstituted coupled differentiation and cell cycle arrest. Thus, CDK inhibitors, in particular p18, are likely to play a pivotal role in controlling cell cycle arrest and cell death in terminal differentiation of late-stage B cells to plasma cells via inhibition of pRb phosphorylation by CDK6.

Apoptosis↗

PubMed1995

A voltage-gated chloride channel in ascidian embryos modulated by both the cell cycle clock and cell volume.

1. Eggs of the ascidian Boltenia villosa have an inwardly rectifying Cl- current whose amplitude varies by more than 10-fold during each cell cycle, the largest amplitude being at exit from M-phase. We examined whether this current was also sensitive to changes in cell volume. 2. Cell swelling, produced by direct inflation through a whole-cell recording pipette, greatly increased the amplitude of the Cl- current at all stages of the cell cycle in activated eggs. Swelling was much less effective in unfertilized eggs. 3. The increase in Cl- current amplitude continued for 10-20 min after an increase in diameter that was complete in 10 s, suggesting the involvement of a second messenger system in the response. 4. Treatment of unfertilized eggs with 6-dimethylaminopurine (DMAP), an inhibitor of cell cycle-dependent protein kinases, increased the amplitude of the Cl- current and its sensitivity to swelling to levels characteristic of fertilized eggs. 5. Osmotically produced swelling also increased Cl- current amplitude in unfertilized eggs. 6. We propose that dephosphorylation renders the Cl- channel functional, and that swelling or activation of the egg increases the sensitivity of the channel to dephosphorylation, perhaps by disrupting its links to the cytoskeleton.

Adenine↗

PubMed1999

Function of trehalose and glycogen in cell cycle progression and cell viability in Saccharomyces cerevisiae.

Trehalose and glycogen accumulate in Saccharomyces cerevisiae when growth conditions deteriorate. It has been suggested that aside from functioning as storage factors and stress protectants, these carbohydrates may be required for cell cycle progression at low growth rates under carbon limitation. By using a mutant unable to synthesize trehalose and glycogen, we have investigated this requirement of trehalose and glycogen under carbon-limited conditions in continuous cultures. Trehalose and glycogen levels increased with decreasing growth rates in the wild-type strain, whereas no trehalose or glycogen was detected in the mutant. However, the mutant was still able to grow and divide at low growth rates with doubling times similar to those for the wild-type strain, indicating that trehalose and glycogen are not essential for cell cycle progression. Nevertheless, upon a slight increase of extracellular carbohydrates, the wild-type strain degraded its reserve carbohydrates and was able to enter a cell division cycle faster than the mutant. In addition, wild-type cells survived much longer than the mutant cells when extracellular carbon was exhausted. Thus, trehalose and glycogen have a dual role under these conditions, serving as storage factors during carbon starvation and providing quickly a higher carbon and ATP flux when conditions improve. Interestingly, the CO2 production rate and hence the ATP flux were higher in the mutant than in the wild-type strain at low growth rates. The possibility that the mutant strain requires this steady higher glycolytic flux at low growth rates for passage through Start is discussed.

Biomass↗

PubMed2006

Therapeutic opportunities to control tumor cell cycles.

Tumor cell proliferation is frequently associated to genetic or epigenetic alterations in key cell cycle regulators. Most human tumors deregulate this pathway to sustain proliferation with independence of external mitogenic factors. In addition, the alteration of cell cycle proteins may confer genomic instability that results in additional mutations in these tumor cells. The frequent alteration of the cell cycle in tumor cells has launched the identification for critical cell cycle regulators as anticancer targets. The inhibition of some cell cycle kinases such as cyclin-dependent kinases (CDKs) or the Aurora and Polo mitotic kinases is currently under study in several preclinical and clinical trials. Similarly, the clinical success of microtubule poisons such as taxol has promoted new applied research in mitosis regulation. Recent investigations have suggested new targets of interest including additional kinases, phosphatases and other mitotic regulators such as microtubule motor proteins (kinesins). Current research in this area will undoubtedly result in new and improved targeted therapies for cancer treatment.

Animals↗

PubMed1980

[3H]ouabain binding during the monolayer organization and cell cycle in MDCK cells.

The specific binding of [3H]ouabain in an epithelial cell line derived from a dog kidney (MDCK) was determined during epithelial reorganization and also during the cell cycle. In suspended cells, the specific binding of [3H]ouabain is reduced 67% compared with the binding obtained in a complete monolayer. After plating back these cells on a permeable support, both transepithelial electrical resistance and [3H]ouabain binding increase with time of incubation. [3H]ouabain binding decreases during S and G2 phases of the cell cycle to reach a minimum during mitosis and increases again during GI. The transepithelial electrical resistance, determined simultaneously, shows the same behavior. The reduction in the number of [3H]ouabain binding sites in two different circumstances in which the epithelial membrane organization is disrupted and the increase in [3H]ouabain binding sites when the epithelial membrane is reorganized are consistent with the hypothesis that the number of pumping sites responsible for the active step in the transepithelial active transport is additional to the number required to maintain the intracellular ionic composition.

Animals↗

PubMed1993

Core proteins of soluble chondroitin sulfate proteoglycans purified from the rat brain block the cell cycle of PC12D cells.

The effects of soluble chondroitin sulfate proteoglycans (CSPGs) purified from the rat brain on proliferation of and neurite outgrowth from PC12D cells (Katoh-Semba et al., J Neurosci Res 17:36, 1987) were investigated. When PC12D cells are cultured under standard conditions, they proliferate with a doubling time of about 2 days, irrespective of the presence or absence of NGF. However, the addition of a mixture of several types of purified soluble brain CSPG (50 nmol uronic acid/ml) to the culture medium prevented the increase in the number of PC12D cells as well as the nerve growth factor (NGF)-induced neurite extension. The dose for 50% inhibition (ID50) was 1.6 nmol/ml for cell proliferation and 2.7 nmol/ml for neurite elongation. The increase in cell number seemed to stop around 6 h after exposure to culture medium supplemented with brain-derived CSPGs, and even substratum-attached CSPGs were able to exert such inhibitory effects. Only brain-type CSPGs, not a cartilage-derived CSPG (PGH) or a hyaluronate-binding PGH, had such inhibitory effects. Furthermore, these inhibitory activities were associated only with the core proteins of brain-derived CSPGs, and not with polysaccharide chains from brain-derived CSPGs. Incorporation of [3H]thymidine into DNA did not decrease for at least the first 12 h. Consequently, the amount of DNA per cell after 48 h of culture was about twofold higher in cells treated with brain CSPGs than in nontreated cells after exposure to the medium with CSPGs. Microspectrophotometry revealed that the population of cells with a high DNA content was greater in the culture treated with brain-derived CSPGs than in the control culture. These findings indicate that purified soluble brain CSPGs block the cell cycle of PC12D cells at the G2 phase with resultant cessation of cell proliferation and the inhibition of neurite outgrowth.

Aggrecans↗

PubMed1992

Deuterium oxide (heavy water) arrests the cell cycle of PtK2 cells during interphase.

Deuterium oxide (D2O, heavy water) exerts an antiproliferative effect on a variety of cells in vitro and on some organisms. This effect is mainly ascribed to a tubulin-mediated antimitotic action. We evaluated the morphology, the mitotic activity, and the dynamics of the cell cycle of PtK2 cells grown in vitro in the presence of 75% D2O for up to eight weeks by microspectrophotometric DNA measurements as well as flow cytometric analysis and a determination of mitotic indices. Substitution of heavy water for water in the culture medium initially increased the mitotic index by a (pro-) metaphase block but after 2 to 3 days of incubation no mitotic figures were seen. Analysis of cells grown for 6 days in medium containing 75% D2O revealed accumulation of cells in S/G2-phase. Extended treatment stabilized the high level of cells in this specific phase, when compared to normal growing cells. Cells grown for 1 to 6 weeks in the presence of D2O remained non-proliferating, nevertheless, they were able to divide again after recovery in non-deuterated medium. The time needed for resumption of the mitotic activity was proportional to the duration of deuterium oxide exposure. Cells incubated for 8 weeks in 75% D2O did not recommence mitotic activity. Light and electron microscopic examination revealed characteristic morphological changes of size and ciliation in PtK2 cells subjected to prolonged deuteration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗