Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “polyploidy”

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 955 records · Page 53Linked to original sources
PubMed1990

Hepatocyte fine structure during maturation and senescence.

Aging is accompanied by a myriad of changes in cell structure, function, and composition. The fact that much of the information concerning age-related alterations in cellular morphology is qualitative precludes meaningful correlations with biochemical changes in order to enhance data interpretation. The mammalian liver has been subjected to both qualitative and quantitative evaluations of hepatocyte structure as a function of aging, i.e., development, maturation, and senescence. Although these data are characterized by considerable variability and, in some instances, blatant contradictions, there exists sufficient agreement in several parameters to permit a consensus in the inbred rat model. Certainly the volume of individual hepatocytes increases with age, and many of the organelle compartments reflect this change. While old rats exhibit a high incidence of polyploidy, there is no definitive evidence to demonstrate a concomitant increase in the binuclear hepatocyte index. Several specific hepatocellular organelles undergo changes in their relative volume or surface area that appear to correlate with functional alterations. The volume density of the lysosomal compartment enlarges significantly during senescence and is accompanied by increased activities of several constituent hydrolases. The hepatic concentration of smooth-surfaced endoplasmic reticulum declines markedly with aging, as does the yield of liver microsomes and the activities of several microsomal enzymes, e.g., mono-oxygenases and glucose-6-phosphatase. However, the responses of the majority of hepatocyte organelles to aging is varied and inconsistent based on the limited data currently available.

Aging↗
PubMed2002

Myocyte ploidy in heart chambers of birds with different locomotor activity.

The ploidy levels of atrio- and ventriculocytes were determined by means of cytofluorimetry in 31 species of birds. The obtained data were collated with postnatal growth rate, heart mass index, and relative masses of heart chambers. The difference between mean ploidy of cardiomyocytes in the left and right atrium is small (7.9+/-0.6%) and comparable to the difference in the masses of these chambers (10.5+/-0.8%). The difference between mean ploidy of atrio- and ventriculocytes is most pronounced for the left and right parts of heart (23.9+/-1.4% and 24.0+/-1.3%, respectively) and corresponds to considerable differences in the average masses of atria and ventricles (4.5-fold and 2.1-fold, respectively). The mean cardiomyocyte ploidy levels in the left and right ventricles differ only slightly, as in the case of atria (by 8.1+/-0.5%), whereas the average mass of the left ventricle is greater by 237+/-16%. This discord can be explained by peculiarities of the growth, which is nonproportionally faster in the left ventricle during the last stage of proliferative heart growth as compared to other chambers. The cardiomyocyte ploidy is higher in birds with a relatively small heart and lower ability to flight. Birds with a high locomotor activity in the adult state have an athletic heart (mass index >1%); they are fast growing, altricial species with a low heart workload in the early postnatal ontogenesis. Birds with a low locomotor activity at the adult state are precocial; they grow slowly and have a high locomotor activity from the first minutes of life. Thus, notwithstanding the fact that a greater elevation of cardiomyocyte ploidy level is acquired under a higher functional load (ventricles vs. atria, left vs. right part of the heart), it is associated with a lower functional potential of the organ at the adult state. The level of somatic polyploidy can be considered an indicator of developmental tensions arising due to a high workload during the growth of a given organ and deficiency of resources invested into this growth. J. Exp. Zool. 293:427-441, 2002.

Animals↗
PubMed2006

A BAC library for the goldfish Carassius auratus auratus (Cyprinidae, Cypriniformes).

A goldfish (Carassius auratus auratus) bacterial artificial chromosome genomic library (BAC library) was constructed from one aquarium-bred male specimen (tetraploid, 4n=100, genome size=3.52 pg/cell). The library consists of 128,352 positive clones with an average insert size of 150.4 kb, covering the genome 11-fold. All clones were spotted onto nylon filters and thus are available for screening of genomic regions of interest, such as candidate genes, gene families, or large-sized syntenic DNA regions of cyprinid species. Preliminary screens with two genes were conducted with hybridizing probes to the genes RAG1 and lgi1. RAG1 is a single-copy gene in zebrafish and is duplicated in C. a. auratus. We found a very close correlation between the number of positive BAC clones and the expected library coverage. Two copies of lgi1 were found in zebrafish. We have detected four different copies in C. a. auratus, not in the expected abundance, which indicates some variation in the coverage of the BAC library. The preliminary screens indicate that many duplicated genes that resulted from the ancient fish-specific genome duplication persist in the tetraploid goldfish genome. Hence, the BAC library will provide a useful resource for the future work on comparative genomics, polyploidy, diploidization, and evolutionary genomics in fishes.

Animals↗
PubMed2006

Phenotypic changes associated with DYNACTIN-2 (DCTN2) over expression characterise SJSA-1 osteosarcoma cells.

DYNACTIN-2 (DCTN2) localises to chromosome 12q13-q15, a region prone to stable amplification in several cancers. Transient DCTN2 overexpression has a significant impact on cellular phenotype primarily due to disruption of the DYNEIN-dynactin motor. Changes reported include alterations of microtubule-directed movement of molecular (e.g. TP53) and organelle (e.g. Golgi) cargoes towards the nucleus, centrosome biology, cellular movement and mitosis with a potential predisposition to mitotic block and polyploidy. These changes would be expected to be of relevance to carcinogenesis. To investigate this, we report the first study of DCTN2 genomic amplification and sustained DCTN2 overexpression in cancer cells. QFMPCR was employed to characterise the extent of chromosome 12q13-q15 amplicons in SJSA-1, SJRH30, U373MG and CCF-STTG1 cancer cells. DCTN2 amplification was present in SJSA-1, U373MG and SJRH30 cells, yet was incomplete at the 5'-end in SJRH30 cells. Only SJSA-1 cells were characterised by DCTN2 overexpression on Western blot analyses. Microscopy studies distinguished SJSA-1 cells by greater DCTN2 immunofluorescence and diminished centrosome and 58K protein Golgi-marker focus compared to SJRH30 cells. Indirect evidence derived from the published work of others indicated that TP53 transport into the nucleus was unimpaired. Furthermore, we observed that SJSA-1 cells were easy to propagate. In conclusion, persistent DCTN2 overexpression can be tolerated in SJSA-1 cancer cells despite phenotypic abnormalities predicted from transient overexpression studies. This preliminary study does not support a major role for DCTN2 overexpression in carcinogenesis, although further studies would be necessary to confirm this.

Adenocarcinoma↗
PubMed1989

Effect of the degree of maturation of mouse oocytes at fertilization: a source of chromosome imbalance.

It has been suggested that the abnormal maturation of the human oocyte during fertilization in vitro may result in chromosome imbalance and induce embryonic loss. Using a mouse model, we have studied the influence of the degree of oocyte maturation (either immaturity or overmaturity) on the chromosome characteristics of embryos at the first-cleavage division. Immature oocytes were obtained 2-3 h or 3-4 h before the expected ovulation time (b.o.). Overmaturation was induced by aging the newly ovulated oocytes in vitro for 3, 6, and 12 h. Our results show a significant decrease in the fertilization rate in the immature groups (65.53% at 2-3 h b.o. and 16.59% at 3-4 h b.o. vs. 78.22% at control) and after 12 h of in vitro aging (69.39%), while a significant increase of this parameter was found at 3 h of aging (82.59%) as compared to the other groups. No significant differences were found in the occurrence of aneuploidy or hyperhaploidy in embryos obtained from immature, newly ovulated, and overmature oocytes. Finally, an increased incidence of polyploidy was detected in immature, 2-3 h b.o. (31.20%), and overmature, 3 h (23.04%) and 6 h (31.61%), groups as compared to the control group (14.59%).

Animals↗
PubMed2005

Development of cloned pig embryos by nuclear transfer following different activation treatments.

This study compared the effects of activation treatments on the development and ploidy of nuclear transferred (NT) pig embryos. After in vitro maturation of oocytes collected from the slaughterhouse, oocytes were enucleated and reconstructed by transfer of donor cells and fusion with three DC pulses (1.4 kV/cm, 20 musec). Oocytes were pulsed thrice electrically with 1.4 kV/cm for 20 musec and NT eggs were divided into three treatment groups: Group 1 (no further treatment), Group 2 (10 mug/mL cycloheximide [CHX], 3 hr), and Group 3 (1.9 mM 6-dimethylaminopurine [DMAP], 3 hr). All the eggs were cultured in sets of 30 in 60 muL drops of NCSU-23 supplemented with 4 mg/mL fatty acid free BSA, and compared for the rates of development and ploidy. The rates of cleavage, development, and total cell number of parthenotes in Group 3 were significantly (P < 0.05) higher than those in Groups 1 and 2. Cleavage rates of NT embryos in Group 1 were significantly (P < 0.05) lower than those in Groups 2 and 3 (73% vs. 81% and 82%, respectively). Development into blastocyst stage and total cell number of NT embryos in Group 3 were significantly (P < 0.05) higher than those in Groups 1 and 2. Although the embryos in Group 3 had higher development, approximately 58% of NT embryos evaluated were abnormal ploidy (6% haploidy, 9% polyploidy, and 42% mixoploid). The results suggested that although DMAP enhanced development and higher cell number, due attention should be paid to abnormal ploidy in pig NT embryos.

Analysis of Variance↗
PubMed2005

Numerical chromosomal abnormalities in equine embryos produced in vivo and in vitro.

Chromosomal aberrations are often listed as a significant cause of early embryonic death in the mare, despite the absence of any concrete evidence for their involvement. The current study aimed to validate fluorescent in situ hybridization (FISH) probes to label specific equine chromosomes (ECA2 and ECA4) in interphase nuclei and thereby determine whether numerical chromosome abnormalities occur in horse embryos produced either in vivo (n = 22) or in vitro (IVP: n = 20). Overall, 75% of 36,720 and 88% of 2,978 nuclei in the in vivo developed and IVP embryos were analyzable. Using a scoring system in which extra FISH signals were taken to indicate increases in ploidy and "missing" signals were assumed to be "false negatives," 98% of the cells were scored as diploid and the majority of embryos (30/42: 71%) were classified as exclusively diploid. However, one IVP embryo was recorded as entirely triploid and a further seven IVP and four in vivo embryos were classified as mosaics containing diploid and polyploid cells, such that the incidence of apparently mixoploid embryos tended to be higher for IVP than in vivo embryos (P = 0.118). When the number of FISH signals per nucleus was examined in more detail for 11 of the embryos, the classification as diploid or polyploid was largely supported because 2,174 of 2,274 nuclei (95.6%) contained equal numbers of signals for the two chromosomes. However, the remaining 100 cells (4.4%) had an uneven number of chromosomes and, while it is probable that many were artefacts of the FISH procedure, it is also likely that a proportion were the result of other types of aneuploidy (e.g., trisomy, monosomy, or nullisomy). These results demonstrate that chromosomally abnormal cells are present in morphologically normal equine conceptuses and suggest that IVP may increase their likelihood. Definitive distinction between polyploidy, aneuploidy and FISH artefacts would require the use of more than one probe per chromosome and/or probes for more than two chromosomes.

Animals↗
PubMed2006

Developmental competence of porcine parthenogenetic embryos relative to embryonic chromosomal abnormalities.

Parthenogenetically activated (PA) embryos exhibit delayed development, a lower blastocyst rate, and less successful development in vitro compared to in vitro fertilized (IVF) embryos. To investigate the possible mechanisms for unsuccessful parthenogenetic development, this study analyzed the chromosome abnormalities and developmental potential of porcine PA embryos. Mature oocytes were electrically activated and cultured in Porcine Zygote Medium-3 (PZM3) supplemented with 3 mg/ml BSA for 6, 7, or 8 days. The percentage of PA blastocysts was lower than that of IVF embryos on days 6 and 7 (16.4 +/- 7.4 vs. 28.7 +/- 3.7; 10.9 +/- 2.8 vs. 21.5 +/- 4.7, P < 0.05; respectively), and the PA blastocysts had significantly fewer nuclei than IVF blastocysts (23.2 +/- 1.8 vs. 29.7 +/- 0.8; 29.7 +/- 3.3 vs. 32.0 +/- 2.4, P < 0.05). The percentage of abnormal PA embryos (including embryos with condensed nuclei, arrested embryos and fragmented embryos) was higher than that of IVF embryos (PA: 52.9 +/- 12.8 vs. 16.4 +/- 7.4 on day 6), and increased with culture time (71.9 +/- 12.1 vs. 10.9 +/- 2.8. on day 7,and 75.0 +/- 22.6 vs. 12.1 +/- 2.3 on day 8, P < 0.05). The Day-6 PA blastocysts (n = 147) were divided into three classes according to the total number of nuclei (<20, 20-39, >40) and into three groups according to the morphological diameter (<150, 150-180, >180 microm). Of the haploid blastocysts, 56.1% had less than 20 nuclei, and 71.5% were less than 150 microm in diameter. Of all (114) blastocysts suitable for analysis, 55.5% displayed chromosomal abnormalities. Among chromosomal abnormalities in PA blastocysts, haploid blastocysts were most prevalent (43.6%), while polyploidy (4.4%) and mixoploidy (7.7%) embryos were less prevalent. Chromosomal abnormalities of porcine PA embryos might contribute to a higher rate of abnormal embryonic development. We suggest that a careful consideration should be given when using the blastocysts with smaller size, and establishing the optimum culture condition for PA embryos development in vitro.

Animals↗
PubMed2005

D-Hillarin, a novel W180-domain protein, affects cytokinesis through interaction with the septin family member Pnut.

By database searches of the Drosophila genome project we have identified D-hil as the fly member of a novel family of W180-domain containing proteins. Immunocytochemistry demonstrated that D-hil is localized to the neuropil of the embryonic CNS, to the cellular cortex of dividing neuroblasts from larval brains, and that it is up-regulated in the cleavage furrow of S2 cells. We show that D-hil distribution overlaps extensively with that of the septin family member Pnut. Cross-immunoprecipitation experiments further indicated that the two proteins may be members of the same protein complex. Analysis of a severe hypomorphic P-element mutation in the D-hil locus suggested that D-hil is a nonessential protein. However, by creating double mutant flies we show that the D-hil locus acts as a modulator of Pnut function by increasing the level of polyploidy of neuroblasts in Pnut(KG00478)/Pnut(KG00478) larval brains. Based on these results we propose that D-hil may function as a regulator of septin function during cytokinesis in the developing nervous system.

Amino Acid Sequence↗
PubMed1992

Assessment of rejection in orthotopic human heart transplantation using proliferating cell nuclear antigen (PCNA) as an index of cell proliferation.

Myocardial biopsies taken during the management of cardiac transplantation were stained for proliferating cell nuclear antigen (PCNA). Counts of PCNA-positive interstitial cells were compared, in retrospect, with the reported histological grade of rejection. Biopsies without rejection had negligible numbers of PCNA-positive cells. Ascending grades of rejection were paralleled by an increase in the number of PCNA-positive cells [grade 1, 13 +/- 35 (mean +/- SD); grade 2a, 38 +/- 40; grade 2b, 91 +/- 75; grade 3, 170 +/- 78]. While highly significant, in statistical terms, the overlap in the counts between different grades means that prediction of rejection from the PCNA count alone is not feasible. Biopsies graded as 0 or 1 and which immediately preceded more severe rejection episodes showed no increase in PCNA-positive cells. The majority of PCNA-positive cells are fibroblasts, although in grade 2b and 3 rejection a small population of PCNA-positive T lymphocytes occurs. PCNA staining is also seen in cardiac myocytes immediately after transplantation, during rejection episodes, and late after transplantation in the absence of rejection. The positive PCNA staining of cardiac myocytes probably reflects DNA synthesis that occurs with the shift toward polyploidy in hypertrophy.

Autoantigens↗
PubMed2001

DNA image cytometry and human papillomavirus (HPV) detection help to select smears at high risk of high-grade cervical lesions.

Three samples were submitted from women undergoing routine screening (n=910): two smears (one for routine cytology and one for DNA image cytometry) and a scrape for human papillomavirus (HPV) testing. DNA histograms were classified as suspect in cases of aneuploidy, polyploidy, and/or diploidy with a high proliferation rate. Follow-up was available in 239 cases. The primary end-point was the presence of a high-grade squamous intraepithelial lesion (HGSIL) at biopsy. Seventy women (7.7%) had a high-risk (HR) HPV infection and a suspect DNA profile. In 77 women with cytological abnormalities, 28 HGSILs were detected: four with a prior diagnosis of ASCUS (all HR-HPV infected including three with a suspect DNA profile), three with smears evocative of LGSIL (all with HR-HPV infection and a suspect DNA profile), and 21 with smears evocative of HGSIL (all with HR-HPV infection and 20 with a suspect DNA profile). During the follow-up period, out of 239 women with a cytologically normal smear at first entry, five developed a HGSIL; all were HR-HPV-positive and four had a suspect DNA profile at the first smear. HR-HPV detection alone gives a sensitivity of 100% for the detection of HGSIL, with a specificity of 84.3%, whereas DNA measurement associated with HPV testing significantly enhances the specificity to 95.4%. Thus, the combination of HPV testing and DNA measurement provides a highly sensitive and specific evaluation of the risk of HGSIL on cervical smears.

Cervix Uteri↗
PubMed2006

Detecting sex chromosome anomalies and common triploidies in products of conception by array-based comparative genomic hybridization.

OBJECTIVES: In recent years, array-based comparative genomic hybridization (array CGH) has moved to the forefront of molecular cytogenetics with its ability to rapidly characterize chromosome abnormalities at resolutions much higher than routine chromosome banding. However, array CGH, like all CGH procedures, has heretofore been deemed unable to detect ploidy, a major cause of fetal demise and spontaneous miscarriage. METHOD: We recently developed a CGH microarray that is designed for detecting aneuploidy and unbalanced chromosome rearrangements. Here, we introduce the use of a Klinefelter male cell line (47,XXY) as a control for array CGH analyses on products of conception (POCs). RESULTS: This approach facilitates the detection of common trisomies and monosomies of the sex chromosomes by reducing the analysis to the identification of single copy gains or losses. Furthermore, in a blinded study, careful interpretation of the microarray results with particular attention to the sex chromosome ratios between the patient sample and the control allowed for the detection of some common triploidies. CONCLUSION: These results suggest that using a chromosomally abnormal cell line in array CGH analysis can be applied to other CGH platforms and that array CGH, when properly performed and analyzed, is a powerful tool that can detect most chromosomal abnormalities observed in a clinical setting including some polyploidies.

Aneuploidy↗
PubMed1983

Treatment of prostatic cancer with LH-RH analogues.

Twenty-one of 32 patients with locally advanced prostatic cancer (stage C) were treated with the LH-RH analogue Buserelin for 7-19 months. After an initial sequence of subcutaneous injections, treatment was continued with intranasal spray application (three daily doses of 400 micrograms each) which ensured maintenance of serum testosterone within the range seen in castrated men. To evaluate the response of the primary tumor to Buserelin, cytological regression was established for all patients by fine-needle aspiration biopsy every 3 months. The cytological results corresponded with those of DNA analyses of single-cell cytophotometry showing a statistically significant drop of the grade of aneuploidy or polyploidy when the prostatic carcinoma responded positively to Buserelin therapy. Seventeen of 21 patients treated with the potent LH-RH analogue showed good therapy response. Four patients with no cytological signs of tumor regression received secondary treatment with estramustine phosphate because of hormone resistence. One patient had to be crossed over to cyclophosphamide, the third drug, for clinical progression after 15 months. Essential side effects have not been observed. Continuous treatment of locally advanced prostatic cancer with Buserelin, combined with close control of the patient, offers not only a real alternative to surgical castration--as the patient is spared the psychical stress of orchiectomy--but also to estrogen therapy with its risk of cardiovascular side effects.

Aged↗
PubMed1986

Androgen and estrogen effect on guinea pig seminal vesicle muscle: a combined stereological and biochemical study.

A combined electron microscopic stereological and biochemical study of the smooth muscle cells of guinea pig seminal vesicles was performed in intact, castrated, castrated and dihydrotestosterone- or estradiol-treated adult animals. Castration led to cell atrophy as determined stereologically by a decreased single cell volume and biochemically by no change in DNA content coupled with an increase in the DNA concentration. Treatment of castrates with dihydrotestosterone restored both the stereological and biochemical parameters of the cell size to slightly supranormal levels. The estrogen-induced increase in muscle weight and DNA content appeared to be due only to hyperplasia of muscle cells and not to a proliferation of fibroblasts or to infiltration by inflammatory cells. In all treatment groups, including the estrogen-treated castrates, more than 95% of the cells in the tissue were smooth muscle cells, and there was no evidence that polyploidy contributed to changes in DNA levels. In addition, in the estrogen-treated muscles, DNA concentration remained high, and the stereologically determined cell size remained low. Therefore, both morphological and biochemical evidence indicate that androgen induces hypertrophy, whereas estrogen induces hyperplasia of muscle cells. The correction of stereological and biochemical data validates the application of stereological cell size determination for smooth muscle cells in organs that hardly can be separated into stromal and epithelial components; eg, the prostate.

Animals↗
PubMed1988

Alteration of cell cycle progression in human leukemia cell line (KOPM-28) induced by 12-o-tetradecanoylphorbol-13-acetate.

Terminal cell differentiation usually results in an irreversible arrest in the G1 phase of the cell cycle and loss of cell renewal ability. Human promyelocytic leukemia HL-60 cells induced with 12-o-tetradecanoylphorbol-13-acetate (TPA) differentiate into monocytes/macrophages and accumulate in G1. We determined the effect of TPA on the growth kinetics of a human leukemia cell line (KOPM-28), which developed several of the characteristics of megakaryocytes in response to TPA, such as the surface antigen complex IIb/IIIa, platelet peroxidase and polyploidy. Cell growth was immediately and completely inhibited by TPA. Flow cytometric analysis of cellular DNA content revealed a gradual decrease in cells in G1 and an accumulation of cells in G2. These data suggest that TPA prolonged G1 and rapidly arrested the cells in G2. Synchronized cells were utilized to further analyze the rapid G2 arrest. Cells arrested with aphidicolin at the G1/S interphase were released, and the effects of TPA (added at different intervals) on cell cycle progression were examined 14 h after release. The results showed that TPA added at the end of the S phase, as well as at the G1/S interphase incompletely but distinctly arrested cells in G2. Moreover, G2 arrest was observed when TPA was added to cells released from a colcemid-induced G2/M block, suggesting that cells already in G2 were inhibited by TPA from moving through M to G1. Since some cells became multi-nucleated in the course of incubation with TPA, this G2 accumulation may have resulted at least in part from a prolongation of the phase or a transient G2 block. These changes in cell cycle progression induced by TPA may be characteristic of and/or related to megakaryocytic differentiation of hemopoietic precursor cells.

Cell Cycle↗
PubMed1990

The control of megakaryocyte ploidy and platelet production: biology and pathology.

Following experimental platelet destruction in animals, large platelets, which are more hemostatically active, are produced before any change in bone marrow megakaryocyte DNA content. When platelet production is stimulated by administration of i.v. vincristine in rats, megakaryocyte ploidy is increased, but mean platelet volume is unchanged. When platelet production and destruction are both stimulated by chronic hypoxia or administration of anti-platelet serum, mean platelet volume and megakaryocyte DNA content are both increased. Since platelet volume is determined primarily at thrombopoiesis, these results imply that mean platelet volume and megakaryocyte DNA content are under separate hormonal control. Therefore, it has been postulated that changes in mean platelet volume occur following changes in platelet production rate, whereas changes in megakaryocyte ploidy are associated with an increased rate of platelet production. In myocardial infarction, platelets have increased mean volume and reduced bleeding time more than in controls. In addition, men with myocardial infarction have increased megakaryocyte size and increased DNA content when compared to controls. These changes are similar to those observed in rabbits following cholesterol feeding. If megakaryocyte polyploidy and mean platelet volume are under separate hormonal control, this suggests that in myocardial infarction, both hormones are active--one stimulating an increased platelet size, the other stimulating the increased megakaryocyte DNA content. In contrast, patients with lymphoma exhibiting a secondary thrombocytosis have no change in mean platelet volume. However, these subjects also have larger bone marrow megakaryocytes when compared to controls. The relation between megakaryocyte size and ploidy implies that the DNA content of these cells is increased in lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Qualitative analysis of chromosomal evolution in a colcemid-treated Chinese hamster population.

Colcemid is known to inhibit the spindle formation and to induce polyploidy and chromosomal nondisjunction. Using a V79 Chinese hamster cell line, we have shown that colcemid is able to induce the formation of cells that are numerically diploid but whose karyotype, when analyzed with the G-banding technique, differs from that of the untreated ones. Even though these cells have a normal chromosomal constitution, they carry alterations in the chromosomal balance and, consequently, in gene dosage. This could result in an abnormal expression of cellular genes or in the expression of new or preexisting recessive mutations, even in a diploid chromosomal constitution.

Aneuploidy↗
PubMed1994

Preferential pericentric lesions and aneuploidy induced in mouse oocytes by the topoisomerase II inhibitor etoposide.

Etoposide (VP-16) is used as an antineoplastic drug in humans. It inhibits topoisomerase II(topoII) activity by forming a ternary complex (DNA-etoposide-topoII). This complex prevents the DNA-strand rejoining activity of topo II, which results in DNA-strand breaks and the formation of structural chromosome aberrations. Topo II activity is also required for removing regions of DNA catenation prior to chromosome segregation. The possibility exists that patients undergoing etoposide chemotherapy may incur genetic damage and, consequently, may be at a greater risk for developing secondary tumors and having genetically abnormal offspring. We studied the ability of etoposide for inducing both structural chromosome aberrations and aneuploidy in mouse oocytes. Different dosages of etoposide were given to female mice at various times before and after human chronic gonadotrophin injection, and ovulated oocytes were collected 17 h later. The proportions of chromatid acentric fragments and of hyperploid metaphase II oocytes were significantly higher (P < 0.01) in the etoposide groups than in concurrent controls. These results indicate that both structural and numerical aberrations can be induced without direct interaction with DNA or with the various organelles associated with chromosome segregation. Additionally, unlike other compounds (vinblastine, colchicine, benomyl, and griseofulvin) that induce both meiotic delay (ovulated metaphase I oocytes and polyploidy) and aneuploidy, etoposide did not cause meiotic delay in oocyte maturation.

Aneuploidy↗