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Results for “Polyploidy”

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PubMed1987

Premature chromosome condensation in human cervical carcinoma.

Premature chromosome condensation was observed in 22 of 150 cases (15%) of cervical cancers studied with G-banding. The percentage of premature chromosome condensation in the tumors ranged from 1.5% to 8.9%. Premature chromosome condensation was present in greater frequency (16 of 22 cases) in tumors showing hyperdiploidy, suggesting that this could be a major mechanism of induction of polyploidy in addition to other operative mechanisms, such as endomitosis and endoreduplication. No relationship, either with the disease stage or prognosis, was evident.

Adult↗

PubMed1988

Nonrandom chromosomal abnormalities in malignant pleural mesothelioma.

Cytogenetic studies were performed on tumor cells from specimens of 30 consecutive patients with malignant pleural mesothelioma. Metaphases for chromosomal G-banding analyses were obtained from 27 of these patients. Clonal abnormalities were detected in 19 patients. Karyotype findings were complex and heterogeneous: aneuploidy, polyploidy, structural abnormalities, and several subclones were seen. The most frequent chromosomal abnormalities were polysomy or partial polysomy 7, monosomy or partial monosomy 22, and rearrangements involving breakpoints at 1p11-22.

Adult↗

PubMed1988

Tubulovillous adenoma of the colon with hyperdiploidy, double-minute chromosomes, and inversion of chromosome 1.

A sessile adenoma of the left flexure of the colon was studied after surgical colectomy. Specimens were obtained for complete histologic evaluation. The tumor consisted of glandular tubes with decreased mucin production and a papillary structure on the luminal aspect. The muscularis mucosa was not involved; there was no carcinomatous focus. Cytogenetic study was carried out on 56 cells; none was normal, 77% were hyperdiploid (52-87 chromosomes), 16% were hypodiploid (18-39 chromosomes), and 7% were paradiploid. The supernumerary chromosomes were chromosomes #3, #6, #13, #19, and #20; chromosome #18 was missing in 80% of the cells. A marker for chromosome #1 resulting from a q21.1-q21.2 break with inversion of the centromere-bearing segment (pter-q21) was observed in 58% of the cells. Twenty-five percent of the cells had double minute chromosomes. Despite the histologically benign nature of the tumor, all the cells showed significant cytogenetic aberrations, some of which are considered to be markers of neoplastic transformation (polyploidy, double minutes, chromosome #1 marker).

Adenoma↗

PubMed1984

Measurement of levels of aneuploidy in mammalian cells using a modified hypotonic treatment.

The use of a short hypotonic treatment can prevent scattering of chromosomes by retaining them within the cell membrane. This technique allows chromosomes to be counted accurately so that hypodiploidy can be assessed as well as hyperdiploidy. Levels of aneuploidy were measured following treatment of a low passage number Chinese hamster fibroblast cell line derived from liver (CH1-L) with colcemid, resulting in a dose-related increase in both aneuploidy and polyploidy. The system may be a valuable assay to extend the biological profile of environmental agents, particularly those that are carcinogenic but do not induce chromosome breakage.

Aneuploidy↗

PubMed1991

Effects of diethylstilbestrol and its methyl ethers on aneuploidy induction and microtubule distribution in Chinese hamster V79 cells.

We previously reported that diethylstibestrol (DES) and its derivatives inhibit the in vitro polymerization of microtubule proteins isolated from porcine brain (Sato et al., 1987). We found that the presence of the free hydroxy group of DES was indispensable for the inhibition of microtubule assembly. In the present investigation, this structure-activity relationship was confirmed by the effects of DES and its methyl ethers on chromosome number and the cellular microtubule architecture of Chinese hamster V79 cells, revealed by fluorescent anti-tubulin antibody. DES induced tetra- and octa-ploidy and DES monomethyl ether induced only tetraploidy at a much slower rate, whereas DES dimethyl ether was found to be completely inactive. Furthermore, DES was more active than its monomethyl ether in disturbing microtubule formation within cells. These results support the initial assumption that polyploidy is largely a consequence of the disturbed assembly of microtubules.

Aneuploidy↗

PubMed1994

Genotoxicity of dithiocarbamates and their metabolites.

Dithiocarbamate fungicides are widely used in agriculture for protection of vegetable crops and seeds. The mutagenicity spectra of ziram, thiram, zineb S-65 and ETU were determined by employing a battery of test systems included the bacterium Salmonella typhimurium (strains TA98, TA100, TA102, TA104, TA1535, TA1538), the yeast Saccharomyces cerevisiae (strain D61.M) and the shallot Allium ascalonicum somatic cells. Plate incorporation assay with S. typhimurium demonstrated direct mutagenicity of ziram in TA100 and thiram in TA100 and TA98 whereas zineb S-65 and ETU were ineffective. Tests for mitotic chromosome malsegregation in S. cerevisiae D61.M gave positive results with thiram, zineb S-69 and ETU. In shallot somatic root-tip cells ziram, thiram and ETU induced different genetic damages e.g. mitotic disturbance, polyploidy and micronuclei.

Allium↗

PubMed1989

Carbaryl-A selective genotoxicant.

Mutagenic effects of carbaryl, a contact insecticide with slight systemic properties, have been investigated employing histidine reversion assay in Salmonella typhimurium strains and in vivo chromosomal aberrations in root meristems of Allium cepa. A detailed investigation revealed that carbaryl did not enhance significantly the frequency of histidine revertants in any of the strains of Salmonella i.e. frameshift mutagen tester (TA98), base pair substitution tester strain (TA1535) and ochre mutant strain (TA102). The supplementation with S9 mix did not have any appreciable effect. S14 prepared from wheat seedlings also did not enhance the reversion frequency significantly. However, carbaryl induced both clastogenic and physiological types of chromosomal aberration. The spectrum of chromosomal aberrations included c-mitosis, stickiness, vagrant chromosomes, polyploidy multi-polarity, delayed anaphases, end to end joining of chromosomes, chromosome breaks, ring chromosomes and anaphase bridges. The frequency of chromosomal aberrations was reduced by transferring the carbaryl treated bulbs to distilled water for 24 and 48 h. Similarly, recovery in the mitotic index was noticed by such transfer. The differences between the two assays may be attributed to differences in the metabolism of the test organisms.

Journal Article↗

PubMed1991

Prolonged G2 phase of breast cancer cells and chromosome damage.

5-bromodeoxyuridine incorporation was studied in metaphase chromosomes from 24 breast tumour specimens, including 23 adenocarcinomas. In these 23 cases, a slow cell cycle was observed, with a long (8 h) G2 phase. This slowing of the cell cycle, which was poorly related to the degree of polyploidy, was significantly related to the number of chromosome anomalies: the cell cycle was particularly slow when many rearranged chromosome were observed. These in vitro findings during the first cell cycle cannot easily be transposed to the in vivo situation. By analogy with Fanconi anaemia, in which both chromosome lesions and a long G2 phase are detected, a DNA repair defect and/or high DNA mutagenesis might exist in breast cancer cells.

Adenocarcinoma↗

PubMed1978

Enolase isozymes in Coho salmon.

1. Analysis of the enolase isozymic distribution has been performed in tissues of the Coho salmon, using electrophoretic separation on cellulose acetate strips followed by localization of enzymatic activity. 2. A total of six electrophoretically distinct forms are seen in Coho salmon in patterns that differ both qualitatively and quantitatively from one tissue to another. 3. The isozymes in skeletal muscle and liver are sufficiently similar to one another that a purification procedure previously developed for trout muscle enolase by Cory & Wold (1966) can be used to partially purify enolase from either of the above-mentioned Coho tissues. The main form of enolase in Coho muscle has an isoelectric point of 7.57. 4. Both liver and skeletal muscle enolases can be reversibly denatured in guanidine HCl and subsequently renatured. Liver enolase appeared to renature somewhat faster than muscle enolase under the same conditions. 5. While polyploidy among salmonids may contribute to the complexity of enolase patterns in fish, the differences in isozymic patterns seen from one tissue to another indicate the presence of distinct, nonallelic genes, probably arising through gene duplication.

Animals↗

PubMed1979

Genome analysis of Amphioxus and speculation as to the origin of contrasting vertebrate genome organization patterns.

1. The genome of Amphioxus was investigated by DNA reassociation techniques for the amount of repetitive and non-repetitive sequences and its pattern of organization. 2. A comparison of the amount of non-repetitive DNA between Amphioxus and the tunicate Ciona intestinalis does not support the hypothesis that the Cephalochordates have arisen from the Tunicates by polyploidy. 3. In the Amphioxus genome repetitive and non-repetitive elements are predominantly arranged in a short period interspersion pattern. Conclusions are presented as to the evolution of contrasting genome organization patterns among vertebrates.

Animals↗

PubMed1983

Molecular and biochemical pharmacology of mitoxantrone.

Evidence has been presented which indicates that Nv: intercalates DNA and additionally causes inter- and intra-strand crosslinking possibly associated with its charged side arms; there is an apparent preference for G-C base pairs; induces single strand and double strand breaks in DNA; strongly inhibits DNA and RNA synthesis; causes nuclear aberrations and chromosomal scattering; induces a block in the G2 phase of the cell cycle with an increase in cellular RNA and polyploidy; is not cell cycle phase-specific with respect to cell kill; does not induce free-radical formation; does not induce lipid peroxidation or superoxide formation; rather it may inhibit ADR-stimulated lipid peroxidation and microsomal superoxide production; does not appear to have a strong potential for cardiotoxicity on the basis of currently postulated mechanisms of action; is capable of inducing cellular resistance in vitro; resistance is associated with an apparent alteration in the cell membrane impairing drug transport into the cell. Although the precise mechanism(s) of tumor cell killing has not been fully defined it is most likely associated with an interaction by Nv with chromosomes resulting in DNA damage, which if not efficiently repaired, will lead to inhibition of nucleic acid synthesis and eventual cell death.

Animals↗

PubMed1982

Cholera toxin: mitogen for Harderian glands of golden hamsters.

1. Within 2 days, a single injection of 10 micrograms cholera toxin induces a 6-20-fold increase in mitotic activity in the Harderian glands of male and female golden hamsters. 2. Neither hypophysectomy nor ovariectomy had any influence on this response. 3. The cellular proliferation does not appear to involve cAMP nor is it the result of stress, nor a release from an early mitotic block. 4. Nuclear polyploidy increases within a few hours after treatment. 5. DNA density per unit area increases within 24 hr and is maintained for at least 3 days.

Adrenocorticotropic Hormone↗

PubMed1984

Mercury-induced segregational errors of chromosomes in human lymphocytes and in Indian muntjac cells.

Segregational errors of chromosomes were studied in human lymphocytes and in Indian muntjac fibroblasts exposed to methylmercury chloride (CH3HgCl) or mercury chloride (HgCl2). The cells were exposed to the mercury compounds only during a limited period of the pre-DNA synthetic stage of the cell cycle or from that stage up to mitosis. In the lymphocytes we observed a clear increase of C-mitotic figures for both mercury compounds and for both exposure times. Segregational errors were, however, much more important after the shorter exposure period. Muntjac fibroblasts appear to be more sensitive to the mercury than are the lymphocytes so that their suitability for the study of C-mitosis may be questionable. The muntjac cells may be an important tool for the study of polyploidy induction.

Aneuploidy↗

PubMed1995

In vitro toxicity assays for dye ligands used in affinity chromatography.

Some reactive textile dyes have been used for years as biomimetic ligands in protein purification. There has been reluctance, however, to use these dyes on a large scale for therapeutically applicable proteins for fear of possible dye leakage and consequent contamination. Therefore, toxicological data are necessary to quantify the level of this hazard. This study deals with a series of in vitro toxicity investigations with eukaryotic cells (growth, polyploidy, etc.) and with prokaryotic cells (Escherichia coli) for genotoxic studies. Both approaches demonstrated a lack of or slight toxicity for Reactive Blue 2 and Reactive Red 120 and their derivatives over the range 10-62.5 micrograms/ml in several assays.

Chromatography, Affinity↗

PubMed1992

Flow cytometric studies in spontaneous abortions. Applications in the medico-legal practice.

In the medico-legal practice differential diagnosis between spontaneous and non-spontaneous abortion is important because causes of pregnancy wastage are often obscure and, moreover, spontaneous abortion is more common than accidental or voluntary. In all the cases in which the cause of abortion is not otherwise detectable and especially in cases of discovery of fetal adnexa, it is necessary to investigate genetic causes. Recently, DNA flow cytometric analysis has been applied in determining the genetic causes of spontaneous abortions. Among karyotypic abnormalities, flow cytometric analysis on paraffin embedded material can detect only polyploidies (triploidy and tetraploidy). Trisomies, monosomies and structural anomalies cannot be detected. In our study we tried to establish whether flow cytometry could be useful in determining the genetic cause of spontaneous abortions, in the lack of any other detectable cause. Histologic examination and flow cytometric analysis were performed on a series of 395 consecutive spontaneous abortions. Histologic examination allowed the detection of a molar pattern in about 9% of cases. DNA flow cytometric analysis showed diploidy in 346 (87.59%) cases, triploidy in 37 (9.36%) cases and tetraploidy in 12 (3.03%) cases. Combined microscopic and flow cytometric analysis revealed abnormalities in 17.5% of cases. A non-diploid pattern is more frequent in molar cases (P less than 0.001). Flow cytometry seems to be interesting in forensic pathology, as it allows the detection of some frequent genetic abnormalities in dead tissues and cells, when other techniques are no longer practicable.

Abortion, Illegal↗

PubMed1993

Reactive astroglia-neuron relationships in the human cerebellar cortex: a quantitative, morphological and immunocytochemical study in Creutzfeldt-Jakob disease.

In order to investigate the role of neuron-glia interactions in the response of astroglial to a non-invasive cerebellar cortex injury, we have used two cases of the ataxic form of Creutzfeldt-Jakob disease (CJD) with distinct neuronal loss and diffuse astrogliosis. The quantitative study showed no changes in cell density of either Purkinje or Bergmann glial cells in CJ-1, whereas in the more affected CJ-2 a loss of Purkinje cells and an increase of Bergmann glial cells was found. The granular layer in both CJD cases showed a similar loss of granule cells (about 60%) in parallel with the significant increase in GFAP+ reactive astrocytes. GFAP immunostaining revealed greater reactivity of Bergmann glia in CJ-2 than in CJ-1, as indicated by the thicker glial processes and the higher optical density. Granular layer reactive astrocytes were regularly spaced. In both CJD cases there was strict preservation of the spatial arrangement of all astroglial subtypes--Fañanas cells, Bergmann glia and granular layer astrocytes. Reactive Fañanas and Bergmann glial cells and microglia/macrophages expressed vimentin, while only a few vimentin+ reactive astrocytes were detected in the granular layer. Karyometric analysis showed that the increase in nuclear volume in reactive astroglia was directly related with the level of glial hypertrophy. The number of nucleoli per nuclear section was constant in astroglial cells of human controls and CJD, suggesting an absence of polyploidy in reactive astroglia. Ultrastructural analysis revealed junctional complexes formed by the association of macula adherens and gap junctions. In the molecular layer numerous vacant dendritic spines were ensheathed by lamellar processes of reactive Bergmann glia. Our results suggest that quantitative (neuron/astroglia ratio) and qualitative changes in the interaction of neurons with their region-specific astroglial partners play a central role in the astroglial response pattern to the pathogenic agent of CJD.

Astrocytes↗

PubMed2005

A method for determining zygosity of transgenic zebrafish by TaqMan real-time PCR.

When producing a genetically modified organism, intended genes are often integrated into a target genome by random insertions. Subsequently, it is often desirable to know the gene copy number of the transgenic organism and the zygosity of its offspring. Because of the random insertions, the estimation can be made only by quantitative measurement of the genes. Even though TaqMan real-time PCR has been used in gene expression analysis, it is routinely used to quantify differences larger than twofold or more than one PCR cycle. In this study, we employed TaqMan quantitative PCR to determine zygosity of transgenic fluorescent zebrafish in which a homozygote and a hemizygote differ by only twofold. We measured relative quantities of the transgene by taking the threshold cycle (Ct) of both the transgene and an internal control zebrafish genomic DNA. Using scatterplots and statistical inference, we demonstrated that homozygotes and hemizygotes could be differentiated unambiguously when multiple measurements were taken. We discuss the relationship between the repetitive measurements and TaqMan precision with a statistical model. The result illustrates that the method can be extended to some areas that require even higher precision such as determining the polyploidy of an organism.

Animals↗

PubMedDate not supplied

Genotoxicity potential of 8-Cl-cyclic adenosine monophosphate assessed with cytogenetic tests in vivo.

BACKGROUND: Growth-modulating noncytotoxic activity of 8-chloro-adenosine 3',5'-cyclic monophosphate (8-Cl-cAMP) showed inhibitory effect on growth of a wide variety of cancer cell lines in vitro and in vivo. To assess possible genotoxic effects of 8-Cl-cAMP, we conducted a study in vivo using male BALB/c mice. METHODS: Clastogenic effects were estimated by bone marrow micronucleus assay and cytogenetic test in adult mice BALB/c strain. 8-Cl-cAMP was administered intraperitoneally (i.p.) to three dose groups including 10 mg/kg body weight (b.w.), 90 mg/kg b.w., and 160 mg/kg b.w., with saline solution as negative control and cyclophosphamide, a known mutagen, and clastogen as positive control during a 7-day period in 24-h intervals. RESULTS: Micronucleus test in vivo results showed consistently increasing dose-dependent pattern increase of dose regime (10 mg/kg body weight [b.w.], 90 mg/kg b.w., and 160 mg/kg b.w.), and increase in frequency of micronuclei in polychromatic erythrocytes (4.88 +/- 0.35, 8.32 +/- 0.57, and 11.74 +/- 0.37) compared to negative control (2.04 +/- 0.28). Quantitative effects are paralleled by structural changes in chromosome morphology. 8-Cl-cAMP induced structural (breaks, gaps, centric rings, acentrics, and Robertsonian translocations) and numerical-type chromosomal aberrations (aneuploidy and polyploidy). CONCLUSIONS: Results of this study demonstrate that 8-Cl-cAMP has genotoxic potential in vivo.

8-Bromo Cyclic Adenosine Monophosphate↗