Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Endoreduplication”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources
PubMed1999

Cell death in paclitaxel-dependent chinese hamster ovary cells is initiated by the loss of telomeric DNA repeats.

We have reported earlier that cell death in a metastatic murine melanoma cell line induced by paclitaxel and its water-soluble conjugates is mediated through the extensive erosion of telomeric repeats. The purpose of this study was to investigate if loss of telomeric repeats was also involved in cell death of Tax-18 and Tax-2-4, two paclitaxel-requiring mutant Chinese hamster ovary (CHO) cell lines. Tax-18 and Tax-2-4 cells were grown in paclitaxel-free culture medium for 24, 48, 72, and 96 h at 37 degrees C and then harvested for cytological preparations. Control cultures of both cell lines were grown in paclitaxel-supplemented medium and harvested simultaneously. We found that: 1) the frequency of telomeric associations in metaphase preparations was increased with the duration of paclitaxel-depleted culture; 2) Tax-18 cells showed a higher incidence (33.0%) of endoreduplicated metaphases at 24 h of paclitaxel-depleted culture than did Tax-2-4 cells, in which endoreduplicated metaphases were rare; 3) the frequency of polyploid cells was increased after 48, 72, and 96 h of paclitaxel-depleted culture for Tax-18 relative to that for Tax-2-4 cells; 4) both cell lines showed reductions in telomeric signals at chromosomal termini, but not in the interphase nuclei; and 5) both cell lines had shorter terminal telomeric restriction fragments after culture in paclitaxel-depleted medium. These results support our earlier observations and indicate that reduction of telomeric repeats is involved in G2/M cell arrest (endoreduplication) followed by severe DNA fragmentation, and then cell death of two CHO mutant cell lines that require paclitaxel for cell division.

Animals↗
PubMed2004

Genome multiplication of extravillous trophoblast cells in human placenta in the course of differentiation and invasion into endometrium and myometrium. II. Mechanisms of polyploidization.

Peculiarities of the structure of interphase nuclei, mitotic activity, and Ki-67 protein intranuclear immunolocalization were studied to elucidate mechanisms of genome multiplication in proliferative and differentiating invasive extravillous trophoblast cells in the human placenta. The presence of numerous chromocenters was shown to be a characteristic feature of proliferative cell nuclei of both villous and extravillous trophoblast. At the beginning of extravillous trophoblast cell differentiation, i.e. in the proximal part of cell columns, some amount of cells with large nuclei containing enlarged chromocenters were found. DNA content was measured simultaneously with counting the number of chromocenters in similarly looking nuclei of squash preparations of placental villi. The increase in the ploidy level up to 4c-8c, accompanied by a slight increase in the number of chromocenters being not proportional to the ploidy level and not exceeding the diploid number of chromosomes of the human genome, was demonstrated. This suggests that genome multiplication of extravillous trophoblast cells may be accomplished by endoreduplication. In addition, pictures of endomitosis were seen at early steps of differentiation of EVT cells. The lack of polyploid mitotic figures or any obvious polyploidizing or restitutional mitoses suggests that these are not of considerable importance in genome multiplication of human EVT cells. However, the prevalence of metaphases at the boundary of the distal part of cell columns suggests that restitutional mitoses may be involved, even partly, in human trophoblast cell polyploidization. At later steps of differentiation, i.e. in the distal part of cell columns, the nuclear structure obviously changes, with a uniform "network" chromatin arrangement prevailing, whereas numerous chromocenters and features of endomitosis are no longer seen. The pattern of Ki-67 protein immunolocalization is also changing along the invasive pathway. In the proliferating stem cells and trophoblast cells of the proximal part of cell columns, Ki-67 was localized in the karyoplasm, chromocenters and numerous small nucleoli, whereas in the distal part of cell columns this protein was detected predominantly in 1-2 large nucleoli. The comparative analysis of the literature data on Ki-67 localization at different stages of cell cycle provided another evidence that EVT cells in the course of invasion may switch to the endoreduplication cycle. In agreement with the relevant report on rodent placentation, our present data suggest that acquirement of an invasive phenotype of EVT cells is accompanied by switching from mitotic division to endoreduplication cycle.

Cell Differentiation↗
PubMed1998

Effects of germanium oxide and other chemical compounds on phenylmercury acetate-induced genotoxicity in cultured human lymphocytes.

Phenylmercury acetate (PMA), which not only causes an elevation of sister chromatid exchanges (SCEs) but also induces high frequency of endoreduplication in human lymphocytes, may be genotoxic to humans. The major aim of our study was to investigate the effects of germanium oxide (GeO2), D-penicillamine (D-PA), dimercaprol (BAL), and diltiazem (DTM) on PMA-induced genotoxicity as quantified by SCEs. All concentrations of the four chemical compounds tested alone did not induce genotoxicity in cultured human lymphocytes. However, GeO2 significantly inhibited PMA-induced genotoxicity in a concentration-dependent manner. Similarly, D-PA at concentrations of 3 microM and 10 microM, and BAL at a concentration of 30 microM produced the antigenotoxic effects. In addition, GeO2 (1.5 microM) significantly reversed an increase of endoreduplication frequency caused by PMA. In a cell cycle kinetic study, GeO2 (0.5-5.0 microM) reversed the inhibition of PMA on the proliferating rate index (PRI) of lymphocytes. On the contrary, both D-PA and DTM at concentrations of 30-300 microM markedly potentiated PMA-induced inhibition of PRI. These findings show that GeO2, D-PA and BAL could antagonize PMA-induced genotoxicity, and GeO2 appears to be the most effective.

Adult↗
PubMed2001

PAL31 expression in rat trophoblast giant cells.

PAL31 is a proliferation-related acidic nuclear protein that belongs to the leucine-rich protein family and is expressed cell-cycle-dependently. Trophoblasts differentiate into the trophoblast giant cells (TGCs) through the unusual type of cell cycle, namely endoreduplication. In the present study, we investigated the spatiotemporal pattern of PAL31 expression in rat placenta and Rcho-1 cell line. The PAL31 mRNA concentration varied in different areas of the placenta, and was barely detectable in the TGC layer. In Rcho-1 cells, although the level of PAL31 mRNA decreased dramatically during differentiation, PAL31 was detected even after differentiation. The site of intranuclear localization of PAL31 mostly overlapped with that of PCNA in the undifferentiated Rcho-1 cells, while they were not overlapped in differentiated cells. Thus, the subcellular localization of PAL31 in Rcho-1 cells significantly changed, and loss of cell cycle dependency after differentiation was noted. PAL31 is suggested to play a role in the endoreduplication distinct from the usual DNA duplication.

Animals↗
PubMed1994

Naphthoquinone cytotoxicity to bluegill sunfish BF-2 cells.

Bluegill sunfish BF-2 fibroblasts were used to evaluate the in vitro cytotoxicities of 1,4-naphthoquinone (NQ), 5,8-dihydroxy-1,4-NQ, and 2,3-dichloro-1, 4-NQ (dichlone); comparisons were made with previously obtained data on the response of human hepatoma HepG2 cells. For both cell types, the sequence of potency was 5,8-dihydroxy-1,4-NQ > 1,4-NQ > dichlone. Dichlone, and, although to a lesser extent, 1,4-NQ and 5,8-dihydroxy-1-4-NQ, induced endoreduplication in the BF-2 cells; for the HepG2 cells, endoreduplication was induced only with dichlone. Exposures to the three NQs reduced intracellular glutathione levels in both cell types. For the BF-2 and HepG2 cells, pretreatments with buthionine sulfoximine (BSO), a glutathione-depleting agent, potentiated the cytotoxicity of 5,8-hydroxy-1,4-NQ and dichlone; pretreatment with dicoumarol, an inhibitor of DT-diaphorase, had no effect on toxicity of these two NQs. Apparently, for these two quinones the predominant metabolic pathway in both the BF-2 and HepG2 cells involved redox cycling via a one-electron reduction reaction, generating reactive oxygen intermediates that consumed intracellular glutathione. Pretreatment of the BF-2 cells with BSO, but not with dicoumarol, potentiated the toxicity of 1,4-NQ, again indicating that metabolism occurred via one electron reduction. However, for the HepG2 cells, pretreatment with dicoumarol, but not with BSO, potentiated the cytotoxicity of 1,4-NQ. Apparently, in the HepG2, as compared to the BF-2, cells, 1,4-NQ was metabolized by DT-diaphorase in a reaction involving a two electron reduction.

Animals↗
PubMed1988

Cytological evidence of defective template in the fragile X chromosome.

In cells of fragile X patients, the changed X segment may appear as a poorly staining region or a gap, or as a deletion, involving one or both chromatids. To find out whether the fragile site represents an incompletely replicated DNA sequence, as has been suggested recently, we analyzed the four chromatids of methotrexate-induced endoreduplicated fragile X chromosomes. Our main observations were: (1) a deleted chromatid was never internal to a poorly staining one; (2) an endoreduplicated X chromosome with a fragile site never included a normal chromatid. These results can be explained by assuming that DNA at the fragile site, when replicated in the presence of methotrexate, may undergo defective replication and give rise to improperly packaged chromatin, appearing as a chromatid with a poorly staining region or a gap in the following metaphase. The same DNA may fail to function as a template in the following S-phase and give rise to a chromatid with a single-stranded segment, appearing as a deleted chromatid in the following metaphase.

Cell Cycle↗
PubMed1992

Genetic evolution of breast cancer: II. Relationship with estrogen and progesterone receptor expression.

The expression of estrogen (ER) and progesterone (PR) receptors was assayed by steroid binding in a series of 95 malignant breast tumors, for which the analysis of chromosome aberrations was performed and allowed the reconstruction of their chromosomal evolution. It was shown that breast tumors undergo a progressive loss of chromosomes, with occasionally one and rarely two endoreduplications. Chromosome losses were often the consequence of rearrangements, and the rate of rearranged chromosomes, which increases progressively, appeared as a possible indicator of tumor progression. The distribution of ER and PR values in the sample of 95 tumors was compared to that of a larger control series of consecutive cases: 598 for ER and 460 for PR. The similarities of the distributions indicated that the sample of 95 tumors was representative of the general population of breast cancers. The levels of ER and PR expression were very strongly and negatively correlated to the rate of rearranged chromosomes, but not to the modal number of chromosomes. However, when tumors having either undergone endoreduplication or not (greater than 50 or less than 51 chromosomes, respectively) were considered separately, a significant correlation between ER and PR expression and chromosome number was found within each group. Finally, breast cancers were subdivided into 4 stages of cytogenetic evolution, from the least to the most evolved: stage 1: less than or equal to 50 chromosomes, less than 25% rearranged chromosomes; stage 2: greater than 50 chromosomes, less than 25% rearranged chromosomes; stage 3: less than or equal to 50 chromosomes, greater than 25% rearranged chromosomes; stage 4: greater than 50 chromosomes, greater than 25% rearranged chromosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
PubMed2006

Light-dependent polyploidy control by a CUE protein variant in Arabidopsis.

Endoreduplication is a special cell cycle that increases ploidy without cell and nuclear division. In plants endoreduplication is essential for development. We isolated a dominant Arabidopsis mutant from activation tagging lines that had increased polyploidy in darkness. This mutant, ipd1-1D (increased polyploidy level in darkness 1-1D), shows longer hypocotyls and increased ploidy levels only in dark-grown seedlings. The corresponding gene encodes a protein that contains a CUE domain variant. IPD1 is specifically expressed in mitotically dividing cells. Furthermore we show that blue and far-red light can suppress the ploidy increase in ipd1-1D and also suppress the reporter expression in IPD1-promoter beta-glucuronidase transgenic plants. These results suggest that IPD1 regulates the endocycle leading to hypocotyl elongation and this function is controlled by blue and far-red light.

Amino Acid Sequence↗
PubMed1981

Spontaneous sister-chromatid exchanges in Chinese hamster cells in vivo and in vitro.

The incidence of sister-chromatid exchanges (SCEs) was studied in Chinese hamster cells. The cells used were an established cell line (Don), an aneuploid secondary culture still exhibiting contact inhibition of growth, a primary culture, bone-marrow cells in vivo, a Don-derived clone having ring chromosomes, and endoreduplicated Don cells. The frequency of SCEs in the presence of bromodeoxyuridine (BUdR) increased in the following order: bone-marrow cells less than Don less than secondary culture cells less than primary culture cells. Marked increases in BUdR concentration induced only slight increases of SCEs. Some ring chromosomes showed Moebius strip and concatenated ring structures, indicating spontaneous occurrence of SCEs in the absence of BUdR. The incidence of spontaneous SCEs observed in ring chromosomes approximates that of SCEs observed in ordinary rod chromosomes in the presence of low dose levels of BUdR. SCEs occurring in the first and second cell cycles were separately counted in endoreduplicated cells. The ratio of single SCEs, which occurred in the second cell cycle, to twin SCEs, which occurred in the first cell cycle, was about 2, when the count of single SCEs was corrected for the induction effect. This implies that uninemy chromatids retain the polarity of DNA when SCEs occur, that bifilarly and trifilarly BUdR-substituted DNA strands give equal numbers of SCEs and that incidence of SCEs is independent of the length of S in the Don cells used here.

Animals↗
PubMed1994

Induction of chromosome aberrations in Syrian hamster renal cortical cells by various estrogens.

Estrogens, both natural and synthetic, have been implicated in carcinogenesis at different organ sites in a variety of animals, including man, for more than six decades. However, the molecular mechanism(s) involved in the carcinogenic action of estrogens still remains both controversial and elusive. Cytogenetic damage in the hamster kidney has been studied after in vivo treatment with either potent or weak estrogens for varying periods. Compared to age-matched untreated control, diethylstilbestrol (DES) treatment resulted in significant increases in the number of chromatid gaps and breaks, chromosome breaks, and endoreduplicated cells in hamster renal cortical cells. These chromosomal aberrations (CA) were cumulative with continued hormone exposure from 1.0 to 5.0 months. However, chromosome exchanges as a result of the breaks were not elevated. After 5.0 months of hormone treatment, potent estrogens such as 17 beta-estradiol and Moxestrol exhibited similar frequencies of CA in the hamster kidney to that found for DES, whereas weak estrogens such as 17 alpha-estradiol and beta-dienestrol exhibited CA frequencies that were not significantly different from untreated levels. Ethinylestradiol treatment for a similar period resulted in significant increases in chromatid gaps, although these did not evolve into increases in either chromatid or chromosome breaks, and in a rise in endoreduplicated cells. These results raise the possibility that the CA generated after estrogen treatment may be involved in renal tumorigenic processes.

Analysis of Variance↗
PubMed1994

Cytogenetics and origins of pediatric germ cell tumors.

We present cytogenetic and DNA fingerprint analysis on 13 new cases of pediatric germ cell tumors; we analyze further four cases we have reported previously. The patients ranged in age from 23 weeks gestation to 16 years. The tumors were located in the ovary, sacrococcygeum, testis, mediastinum, and the craniofacial region, and represented benign, immature, and malignant cases. All of the new cases had a normal diploid karyotype. We have previously reported on multiple genetic mechanisms of origin for ovarian germ cell tumors, namely meiosis I nondisjunction, meiosis II nondisjunction, endoreduplication of a haploid ovum, mitotic division of premeiotic germ cell, and fusion of two ova. To determine the origin of extragonadal and testicular GCTs, Q-band centromeric heteromorphisms and DNA markers were analyzed in the host and the cognate tumor. Our data suggest that extragonadal and testicular GCTs do not arise by a meiosis I or II error, or by endoreduplication; rather, they arise mitotically from either a somatic or a germ cell.

Adolescent↗
PubMed1996

Effect of trivalent and pentavalent arsenic in causing chromosome alterations in cultured Chinese hamster ovary (CHO) cells.

Sodium salts of trivalent and pentavalent arsenic were tested for their effect in inducing chromosome aberrations and sister-chromatid exchange (SCE) in cultured Chinese hamster ovary (CHO) cells. It was discovered that arsenite (As 3) produced excessive endoreduplication of the chromosomes at higher levels. No endoreduplication was observed with arsenate (As 5) treatment. These agents also elevated the frequencies of SCE, but less so compared to aberrations. The results obtained indicate that arsenic may be carcinogenic in animal system.

Animals↗
PubMed2005

The cytoplasmic expression of E-cadherin and beta-catenin in bovine trophoblasts during binucleate cell differentiation.

Binucleate cells are endocrine cells generated by the acytokinesis and endoreduplication of the trophectoderm in the ruminant placenta. These cells are migratory and secrete hormones into the maternal circulation after fusing with uterine epithelial cells. In this study, we performed immunohistochemistry for E-cadherin and beta-catenin in bovine placenta and a bovine trophoblast cell line (BT-1). We found that E-cadherin and beta-catenin were distributed not only at the cell to cell boundary but throughout the cytoplasm in binucleate cells, although they were concentrated at the cell to cell boundary in epithelial cells in bovine placenta. Moreover, beta-catenin was detected in the nuclei of binucleate cells. Binucleate cells after fusion with uterine epithelial cells (feto-maternal hybrid cells) in the maternal side showed no intracellular expression of E-cadherin and beta-catenin. The transformation into binucleate cells in the BT-1 cell line was also accompanied by the cytoplasmic accumulation of E-cadherin and beta-catenin. We further demonstrated that levels of cytoplasmic beta-catenin were well correlated with the DNA content of binucleate cells in BT-1. The dynamic changes in the distribution of E-cadherin and beta-catenin suggest an important role in binucleate cells, including the rearrangement of cadherin-mediated cell adhesions during cell migration and the onset of endoreduplication probably via the nuclear transfer of beta-catenin.

Actins↗
PubMed1997

Characterization and cytogenetic analysis of Japanese Black calves produced by nuclear transfer.

To confirm the normality of the Japanese Black calves produced by nuclear transfer, we examined the properties of such calves at parturition and analyzed their karyotypes. Thirty Japanese Black calves were produced by nuclear transfer; 3 of these calves (10.0%) required assisted delivery while 1 calf (3.3%) died soon after birth. Average birth weight was 31.0 +/- 1.8 kg and gestation period was 286.4 +/- 1.0 d (mean +/- SEM). None of the nuclear transfer calves showed external malformations. Within sets of cloned nuclear transfer calves, which were genetically identical, birth weights varied by up to 20.5 kg. Among singleton Japanese Black calves, the mean birth weight of nuclear transfer calves was significantly greater (P < 0.05) than that of calves produced by in vivo-derived embryo transfer. Cytogenetic analysis of 23 Japanese Black nuclear transfer calves revealed the presence of 2N 4N mosaicism in 21 of the nuclear transfer calves. The frequency of occurrence of tetraploidy was unrelated to birth weight. Endoreduplication was observed in 1 Japanese Black nuclear transfer calf, and the frequency of occurrence of the endoreduplication in this calf was 0.5% (1/209). We conclude that there was no external malformation or chromosomal aneuploidy in Japanese Black nuclear transfer calves, but the mean birth weight of nuclear transfer calves was heavier than that of in vivo-derived embryo transfer calves in both sexes, and a variation of birth weight within sets of nuclear transfer calves cloned from the same embryo was recognized.

Journal Article↗
PubMed1996

Cell senescence and a mechanism of clonal evolution leading to continuous cell proliferation, loss of heterozygosity, and tumor heterogeneity: studies on two immortal colon cancer cell lines.

Extensive karyotypic analysis was performed on early and late passages of two continuous human cell lines, SW480 and SW620, that were derived from the same colon cancer patient. We cultivated these two cell lines in vitro for a period of 24 months and periodically examined their chromosome constitution. SW480 cells, from passage 138, were injected subcutaneously into 20 nude mice. The tumors that grew in nude mice were then cultivated in vitro for several passages to compare histopathologic findings and tumor growth patterns with clonal chromosomal profiles. Despite some karyotypic diversity, the two cell lines exhibited common marker chromosomes and followed similar patterns of evolution. During subsequent passages, acquisition of new chromosomal abnormalities gave rise to sidelines with a near-diploid genome that frequently underwent endoreduplication. Genomic instability seemed to play an important role in the emergence, growth, and subsequent elimination of the heterogenous sidelines by selection, clonal expansion, and cell death by senescence. Despite continuous growth, both the cell lines occasionally showed telomeric associations and random dicentric and multicentric formations. These lesions were considered evidence of cell senescence and were related to the disappearance of particular sidelines through evolution. Successful evolutionary steps were characterized by elimination of pre-existing marker chromosomes that were subsequently replaced in the karyotype by their cytologically intact homologous chromosomes possibly after selective endoreduplication. Frequent loss of heterozygosity for the chromosomes taking part in this process is postulated. We suggest that one of the mechanisms by which cancer cells bypass senescence may be related to their potential for continuous clonal diversification.

Animals↗
PubMed1994

Proliferating cell nuclear antigen (PCNA) expression of megakaryocytopoiesis in normal human bone marrow and reactive lesions with special emphasis on HIV-myelopathy.

A morphometric analysis was performed on bone marrow trephine biopsies using sequential double-immunostaining, to evaluate endoreduplicative activity of megakaryocytopoiesis. A total of 104 marrow specimens were studied with employment of monoclonal antibodies PC10 (anti-proliferating cell nuclear antigen-PCNA) and Y2/51-CD61 (anti-platelet glycoprotein IIIa). In addition to the control group patients included non-specific inflammatory changes, HIV-myelopathy with normal or decreased platelet counts, idiopathic thrombocytopenic purpura (ITP), and finally reactive thrombocytosis (TH). To exclude an undue overexpression of PCNA, in a comparative pilot study we also applied MIB1 (Ki-67 antigen) on normal bone marrow specimens. In accordance with the various modalities of cell-cycle marker expression, no significantly different findings were disclosed. PCNA-labelling index was relatively low, ranging from 0.8 to 1.7% of the total megakaryocytopoiesis (promegakaryoblasts to mature platelet-shedding megakaryocytes). A significant relationship between megakaryocyte size and PCNA-expression was determinable. This implies that some of the cases with a prevalence of small megakaryocytes, like ITP, have the tendency to show a higher proportion of positively-stained cells. Moreover, this feature confirms a hypothesis postulating a decrease in the time for DNA-synthesis (S-phase) and a relative prolongation of the G1/G2-phases of the cell-cycle at higher ploidy levels (large-sized megakaryocytes). On the other hand, it may be speculated that some of the hyperpolyploid giant megakaryocytes may have reached their endstage of endoreduplication and enter into G0-phase. In comparison with the control group and the other entities under study, a significant reduction of PCNA-reactivity was recognizable in HIV-myelopathy accompanied by thrombocytopenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2001

CPR5 is involved in cell proliferation and cell death control and encodes a novel transmembrane protein.

Plants often respond to pathogens by sacrificing cells at the infection site. This type of programmed cell death is mimicked by the constitutive pathogene response5 (cpr5) mutant in Arabidopsis in the absence of pathogens, suggesting a role for CPR5 in programmed cell death control. The analysis of the cellular phenotypes of two T-DNA-tagged cpr5 alleles revealed an additional role for CPR5 in the regulation of endoreduplication and cell division. In cpr5 mutant trichomes, endoreduplication cycles stop after two rounds instead of four, and trichome cells have fewer branches than normal. Eventually, cpr5 trichomes die, the nucleus disintegrates, and the cell collapses. Similarly, leaf growth stops earlier than in wild-type, and, frequently, regions displaying spontaneous cell death are observed. The cloning of the CPR5 gene revealed a novel putative transmembrane protein with a cytosolic domain containing a nuclear-targeting sequence. The dual role of CPR5 in cell proliferation and cell death control suggests a regulatory link between these two processes.

Apoptosis↗
PubMed2003

Active localization of the retinoblastoma protein in chromatin and its response to S phase DNA damage.

The Rb protein suppresses development of an abnormal state of endoreduplication arising after S phase DNA damage. In diploid, S phase cells, the activity of protein phosphatase 2A (PP2A) licenses the stable association of un(der)phosphorylated Rb with chromatin. After damage, chromatin-associated pRb is attracted to certain chromosomal replication initiation sites in the order in which they normally fire. Like S phase DNA damage in Rb(-/-) cells, specific interruption of PP2A function in irradiated, S phase wt cells also elicited a state of endoreduplication. Thus, PP2A normally licenses the recruitment of Rb to chromatin sites in S phase from which, after DNA damage, it relocalizes to selected replication control sites and suppresses abnormal, postdamage rereplicative activity.

Cell Nucleus↗