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PubMed2001

A multivalent pairing model of linkage analysis in autotetraploids.

Polyploidy has been recognized as an important step in the evolutionary diversification of flowering plants and may have a significant impact on plant breeding. Statistical analyses for linkage mapping in polyploid species can be difficult due to considerable complexities in polysomic inheritance. In this article, we develop a novel statistical method for linkage analysis of polymorphic markers in a full-sib family of autotetraploids. This method is established on multivalent pairings of homologous chromosomes at meiosis and can provide a simultaneous maximum-likelihood estimation of the double reduction frequencies of and recombination fraction between two markers. The EM algorithm is implemented to provide a tractable way for estimating relative proportions of different modes of gamete formation that generate identical gamete genotypes due to multivalent pairings. Extensive simulation studies were performed to demonstrate the statistical properties of this method. The implications of the new method for understanding the genome structure and organization of polyploid species are discussed.

Algorithms↗

PubMed2002

General models of multilocus evolution.

In 1991, Barton and Turelli developed recursions to describe the evolution of multilocus systems under arbitrary forms of selection. This article generalizes their approach to allow for arbitrary modes of inheritance, including diploidy, polyploidy, sex linkage, cytoplasmic inheritance, and genomic imprinting. The framework is also extended to allow for other deterministic evolutionary forces, including migration and mutation. Exact recursions that fully describe the state of the population are presented; these are implemented in a computer algebra package (available on the Web at http://helios.bto.ed.ac.uk/evolgen). Despite the generality of our framework, it can describe evolutionary dynamics exactly by just two equations. These recursions can be further simplified using a "quasi-linkage equilibrium" (QLE) approximation. We illustrate the methods by finding the effect of natural selection, sexual selection, mutation, and migration on the genetic composition of a population.

Emigration and Immigration↗

PubMed2025

Accurate identification of abnormal ploidy using an artificial intelligence model in preimplantation genetic testing.

STUDY QUESTION: Can ultra-low-coverage whole-genome sequencing (ulc-WGS) accurately identify abnormal ploidy during preimplantation genetic testing (PGT)? SUMMARY ANSWER: The artificial intelligence (AI)-based PGT-Plus model demonstrates high accuracy in ploidy detection, offering a cost-effective solution that enhances clinical utility of PGT. WHAT IS KNOWN ALREADY: The predominant PGT for aneuploidy can identify chromosomal aneuploidies but cannot determine ploidy status. Transferring embryos with ploidy abnormalities can result in miscarriage and molar pregnancy. On the other hand, in ART, fertilization is assessed by morphological pronuclear assessment at the zygote stage. However, it has a low specificity in the prediction of abnormal ploidy status and embryos deemed abnormally fertilized can yield healthy pregnancies. Accurately identified abnormal ploidy in PGT-A can resolve current limitations and expand the utility range of PGT-A. Several studies have identified ploidy abnormalities; however, they were mainly based on single-nucleotide polymorphism (SNP) arrays or needed to combine additional targeted-next-generation sequencing (NGS) information. Studies based on ulc-WGS remain scarce. STUDY DESIGN SIZE DURATION: The study consisted of two stages: methodology establishment and validation. An AI model, named PGT-Plus, was developed using 653 samples with known ploidy status, which was further validated using 792 different ploidy status samples. In the clinical application stage, the approach was used to analyse the ploidy status of 19 103 normally fertilized PGT blastocysts and 140 single pronucleus (1PN)-derived blastocysts collected between May 2022 and December 2023. All blastocysts were tested using trophectoderm biopsy and NGS. PARTICIPANTS/MATERIALS SETTING METHODS: The methodology is based on the ulc-WGS data. First, based on samples with known ploidy status: the heterozygosity rate of high-frequency biallelic SNPs, the likelihood ratio (LLR) of alleles was calculated under different assumptions ('both parental homologs' [BPH] from a single parent, 'single parental homolog' [SPH] from each parent, disomy, and monosomy) by leveraging allele frequencies and linkage disequilibrium (LD) measured in the 1000 genomes project database. Twenty-three continuous candidate features derived from heterozygosity rates and LLRs of chromosomes or selected windows were included to establish the ploidy prediction AI model. Gini importance analysis and multicollinearity mitigation was performed for feature selection, then the performance of Random Forest (RF), Support Vector Machine (SVM), and Logistic Regression for modelling was compared. Subsequently, the parameter optimization was performed based on the RF model. Ploidy constitution concordance was evaluated in known ploidy status samples. The frequency of abnormal ploidy in normal fertilized PGT blastocysts and 1PN-derived blastocysts (including conventional IVF and ICSI) was evaluated. MAIN RESULTS AND THE ROLE OF CHANCE: Eleven features were collected for model architecture compared to SVM and Logistic Regression; RF achieved superior performance for ploidy detection. The AI model achieved an AUC of 1 for genome-wide-uniparental diploidy (GW-UPD), 1 for triploidy, and 0.99 for diploidy. For the 792 validation samples, 99.5% of samples were successfully detected using the AI model, and the model showed 100% accuracy for ploidy classification. In the clinical application stage, out of 19 103 PGT samples, 19 069 were successfully analysed using the model, with 110 (0.57%) identified as having abnormal ploidy embryos. Among these, 12.7% (14/110) were identified as GW-UPD, and 87.3% (96/110) were triploid. Among 5563 diploid blastocysts transferred, 3478 clinical pregnancies were achieved. Subsequent ploidy analysis was performed for 217 spontaneous abortion and 935 prenatal diagnostic samples, and no abnormal ploidy was identified. Furthermore, of the 140 1PN embryos tested, 40 (28.6%) exhibited GW-UPD, 3 (2.1%) exhibited triploidy, and 97 (69.3%) were determined to be biparental and normally fertilized. Among the 97 biparental embryos, 46 were diploid, 11 were mosaic, and 40 were aneuploid. In terms of the insemination pattern, the percentage of abnormal ploidy in ICSI was significantly higher than in conventional IVF (P < 0.01, 37.1% vs. 2.9%, respectively). With full informed consent, 20 patients without euploidy from normal fertilization chose 1PN-derived biparental and diploid blastocysts to transfer, resulting in 10 clinical pregnancies and 9 ongoing pregnancies. LARGE-SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: Some rare ploidy abnormalities, such as polyploidy with an equal number of identical sets of chromosomes and ploidy mosaicism cannot be accurately identified. Moreover, the origin of abnormal ploidy was not identified due to the unavailability of DNA from both parents. WIDER IMPLICATIONS OF THE FINDINGS: The PGT-Plus AI model provides a ploidy evaluation method based on the conventional PGT-A data and integrates directly into standard PGT-A workflows. Clinical utility results suggest that the model is a valuable tool for identifying embryos with abnormal ploidy in PGT-A and rescuing normal diploid embryos from abnormally fertilized embryos. These findings demonstrate that PGT-Plus significantly enhances the diagnostic accuracy of PGT. STUDY FUNDING/COMPETING INTERESTS: This study was supported by grants from Major Scientific Program of CITIC Group (No. 2023ZXKYB34100, to Ge.L.), Hunan Provincial Grant for Innovative Province Construction (2019SK4012), Hunan Xiangjiang New District (Changsha High-tech Zone) key core technology research project in 2023, and Science Foundation of Hunan Province (Grant 2023JJ30422). All authors declared no conflicts of interest..

artificial intelligence↗

PubMed1997

Comparison of ultrasonographic findings in spontaneous abortions with normal and abnormal karyotypes.

To determine whether ultrasonographic findings can predict the karyotype of spontaneous abortions, 137 pregnancies (54 spontaneous, 83 assisted ovulatory cycles) that subsequently aborted and had chromosome analysis performed on the products of conception were studied ultrasonographically. Transvaginal ultrasound was performed using an Acuson 128XP/10 with 7.5 MHz probe. The numbers of empty gestational sacs, small and normal for gestational size, embryonic poles and embryos with documented cardiac activity were calculated. The frequency of each of these findings in pregnancies with normal and abnormal karyotypes was compared. Of the 137 spontaneous abortions, 51 had normal chromosome analyses and 86 had abnormal karyotypes (68 aneuploidies and 18 polyploidies). Ultrasonographic findings in the 51 karyotypically normal pregnancies included 16 (31%) with empty gestational sacs, and 35 (69%) with embryonic poles, of which 24 (69%) were at least 1 week smaller than expected for gestational age and 11 (31%) were the expected size. Embryonic cardiac activity was documented in 22 (63%) of the 35 embryonic poles. Amongst 86 pregnancies with abnormal karyotypes, similar frequencies of ultrasound findings were found: 23 (27%) with empty gestational sacs, 42 (67%) with embryonic poles smaller than expected for gestational age, and 50 (79%) embryos lost after documentation of embryonic cardiac activity. No differences in the frequency of ultrasonographic findings of empty gestational sacs, small embryonic pole and embryonic cardiac activity were observed between karyotypically normal and abnormal spontaneous abortions. Ultrasonographic findings cannot predict the karyotype of spontaneous abortions.

Abortion, Spontaneous↗

PubMed1997

Will preimplantation genetic diagnosis assist patients with a poor prognosis to achieve pregnancy?

PGD (preimplantation genetic diagnosis) of aneuploidy for chromosomes X, Y, 13, 18 and 21 was carried out on 196 embryos from 36 infertile patients classified with a poor prognosis due to (i) maternal age, (ii) repeated in-vitro fertilization (IVF) failures and (iii) mosaic karyotype. The percentage of abnormal embryos was comparable in the three groups of patients: maternal age 63%, repeated IVF failure 57%, and mosaic karyotype 62%. The analysis of the overall data revealed an increased incidence of abnormal embryos in the older age categories (predominantly due to aneuploidy), even in embryos at the 7- to 8-cell stage. In addition, the percentage of chromosomally abnormal embryos was directly proportional to the number of IVF failures, where the increase in chromosomal abnormalities was not correlated to aneuploidy but to other aberrations such as mosaicism and polyploidy. Following PGD, 28 patients had at least one embryo transferred that appeared normal by fluorescent in-situ hybridization (FISH). Four clinical pregnancies resulted, with an implantation rate of 10% per normal embryo. In conclusion, the high rate of chromosomally abnormal embryos in poor prognosis patients may have been the cause of implantation failure in their previous IVF cycles. Therefore, the possibility of transferring embryos with a normal FISH complement could improve the chance of pregnancy in this category of patients.

Adult↗

PubMed1995

The cytogenetic analysis of human zygotes and preimplantation embryos.

A review of cytogenetic studies on human zygotes and preimplantation embryos is presented. This survey documents the high incidence of chromosomal abnormalities in embryos in vitro. Up to date, 914 zygotes and embryos have been karyotyped. The rate of abnormalities is significantly higher in morphologically poor-quality embryos than in good-quality embryos (86.6 and 36.6% respectively). In both groups, aneuploidy is the most frequently observed abnormality. In addition, various types of aberrations such as polyploidy, haploidy, mosaicism or fragmentation are also found. Among tripronucleated zygotes, 81.9% display chromosomal abnormalities. Data suggest that some parameters of IVF procedures might be responsible for the occurrence of some abnormalities.

Aneuploidy↗

PubMedDate not supplied

Chromosome abnormalities in human embryos.

The presence of numerical chromosome abnormalities in human embryos was studied using fluorescence in-situ hybridization with four or more chromosome-specific probes. When most cells of an embryo are analysed, this technique allows differentiation to be made between aneuploidy, mosaicism, haploidy and polyploidy. Abnormal types of fertilization, such as unipronucleated, tripronucleated zygotes and zygotes with uneven pronuclei, were studied using this technique. We have found a strong correlation between some types of dysmorphism with chromosomal abnormalities. In addition, the more impaired the development of an embryo, the more chromosomal abnormalities were detected in those embryos. Maternal age and other factors were linked to an increase in chromosome abnormalities (hormonal regimes, temperature changes), but not to intracytoplasmic sperm injection.

Aneuploidy↗

PubMedDate not supplied

Anther culture-derived regenerants of durum wheat and their cytological characterization.

Anther culture is being increasingly used in cereal crop improvement both as a source of haploids and for inducing new genetic variation. We studied the androgenetic ability and regenerability of 10 cultivars of durum wheat (Triticum turgidum L., 2n = 4x = 28; AABB), using three different growth conditions and four media. From a total of 86,400 anthers cultured, 324 plants were obtained: 248 green and 76 albino. Genotype, growth condition, and media significantly affected anther response and callus production; interactions were also significant. Green plant regeneration was influenced significantly by genotype and growth condition, as well as by genotype and growth condition interactions. Albino plant regeneration was significantly affected only by growth condition. Regenerants showed gametoclonal/somaclonal variation. Differences in morphology, growth habit, adult plant height, spike size, and development of spikes at nodes were observed. Mitotic and meiotic chromosomes were studied by conventional staining and fluorescent genomic in situ hybridization techniques. Chromosome numbers of the regenerants ranged from 14 to 70. All 76 haploid plantlets (2n = 2x = 14; AB) were albino. Some of the 28-chromosome regenerants were also albino. Chromosome number in the green plantlets ranged from 28 to 70. Chromosome number also varied in regenerants originating from the same callus. Both intergenomic and intragenomic multivalents were observed. An interesting feature was the preferential multiplication of B-genome chromosomes, which formed multivalents (trivalents, quadrivalents, and hexavalents). We observed several chromosomal abnormalities, which seemed to increase with the level of polyploidy. Translocations, dicentric chromosomes, chromatid exchanges, and Robertsonian translocations involving the A- and B-genome chromosomes were observed. Chromosome breakages resulting in centric and acentric fragments, and telocentrics were observed. Chromosome multiplication and structural aberrations induced during culture may constitute the bases of gametoclonal and somaclonal variations.

Chromosome Banding↗

PubMedDate not supplied

FISH mapping of the 5S and 18S-28S rDNA loci in different species of Glycine.

Wild germplasms are often the only significant sources of useful traits for crops, such as soybean, that have limited genetic variability. Before these germplasms can be effectively manipulated they must be characterized at the cytological and molecular levels. Modern soybean probably arose through an ancient allotetraploid event and subsequent diploidization of the genome. However, wild Glycine species have not been intensively investigated for this ancient polyploidy. In this article we determined the number of both the 5S and 18S-28S rDNA sequences in various members of the genus Glycine using FISH. Our results distinctly establish the loss of a 5S rDNA locus from the "diploid" (2n = 40) species and the loss of two from the (2n = 80) polyploids of GLYCINE: A similar diploidization of the 18S-28S rDNA gene family has occurred in G. canescens, G. clandestina, G. soja, and G. max (L.) Merr. (2n = 40). Although of different genome types, G. tabacina and G. tomentella (2n = 80) both showed two major 18S-28S rDNA loci per haploid genome, in contrast to the four loci that would be expected in chromosomes that have undergone two doubling events in their evolutionary history. It is evident that the evolution of the subgenus Glycine is more complex than that represented in a simple diploid-doubled to tetraploid model.

Chromosomes↗

PubMed2005

Genome size evolution in New Zealand triplefin fishes.

The genome sizes of 18 species of New Zealand triplefin fishes (family Tripterygiidae) were determined by flow cytometry of erythrocytes. The evolutionary relationships of these species were examined with a molecular phylogeny derived from DNA sequence data based on 1771 base pairs from fragments of three mitochondrial loci (12S and 16S ribosomal RNA, and the control region) and one nuclear locus (ETS2). Haploid genome sizes ranged from .85 pg (1C) to 1.28 pg with a mean of 1.15 +/- .01pg. Genome size appeared to be highly plastic, with up to 20% variation occurring within genera and a 50% difference in size between the smallest and the largest genome. No evidence was found to indicate polyploidy as a mechanism for speciation in New Zealand triplefins. Factors suggested to influence genome sizes of other organisms, such as morphological complexity, neoteny, and longevity, do not appear to be associated with shifts in the genome sizes of New Zealand triplefins.

Animals↗

PubMed2006

Infraspecific DNA methylation polymorphism in cotton (Gossypium hirsutum L.).

Cytosine methylation is important in the epigenetic regulation of gene expression and development in plants and has been implicated in silencing duplicate genes after polyploid formation in several plant groups. Relatively little information exists, however, on levels and patterns of methylation polymorphism (MP) at homologous loci within species. Here we explored the levels and patterns of methylation-polymorphism diversity at CCGG sites within allotetraploid cotton, Gossypium hirsutum, using a methylation-sensitive amplified fragment length polymorphism screen and a selected set of 20 G. hirsutum accessions for which we have information on genetic polymorphism levels and relationships. Methylation and MP exist at high levels within G. hirsutum: of 150 HpaII/MspI sites surveyed, 48 were methylated at the inner cytosine (32%) and 32 of these were polymorphic (67%). Both these values are higher than comparable measures of genetic diversity using restriction fragment length polymorphisms. The high percentage of methylation-polymorphic sites and potential relationship to gene expression underscore the potential significance of MP within and among populations. We speculate that biased correlation of methylation-polymorphic sites and genes in cotton may be a consequence of polyploidy and the attendant doubling of all genes.

DNA Methylation↗

PubMed1976

Patterns of invasive growth in vitro. Human decidua graviditatis confronted with established human cell lines and primary human explants.

Human decidua graviditatis was used as a receptor tissue to demonstrate invasive properties of human cells in vitro. In the confrontation between decidua and established cell lines of tumors and of normal origin as well as primary explanted cells, we noted differences in the cells' interactions with decidual tissue. The two original tumor cell lines, HeLa (carcinoma) and AFi (sarcoma), and a spontaneously transformed lymphoblastoid cell line showed aggressiveness, i.e., invasion, rapid proliferation, injury, and destruction of the decidual tissue. Strain HeLa S3 and two established cell lines, FL (amnion) and Girardi Heart, which are regarded as transformed cells because of their increased mitotic rate and polyploidy, exhibited various degrees of aggressiveness but did not invade. Freshly explanted fetal lung and endometrium caused no injury to the receptor tissue and were included in the decidual tissue.

Amnion↗

PubMed1977

Correlation of cell kinetic findings with morphology of non-Hodgkin's malignant lymphomas.

Kinetic studies were carried out on 6 benign and 37 malignant lymph nodes from patients with non-Hodgkin's malignant lymphomas (ML). The labeling index, DNA content, and cell distribution through the cell cycle were analyzed in the ML, which were classified according to the Kiel classification. Approximately 90% of the ML studied showed a clear diploidy; the only cases of polyploidy were limited to some centroblastic-centrocytic ML with more than 30% malignant centroblasts and to be single centroblastic ML. The labeling indexes ranged from 0.05 to 33%. No correlation was found between the proliferative rate and the degree of ploidy, while a grading of labeling index was found in relation to the three main DNA distribution patterns observed (i.e., G1 peak, S accumulation, and bimodal distribution through the cell cycle). From a kinetic point of view, the most heterogeneous groups were the lymphoplasmacytoid (subtype polymorphous) and centroblastic-centrocytic ML, where the degree of proliferation increased as the mixture of cell type (relative to the former group) and the malignant centroblastic component (relative to the latter group) increased.

Adolescent↗

PubMed1977

Comparative chromosome study of normal mammary tissue, carcinogen-induced mammary tumors, and hyperplastic alveolar nodules in the rat: Brief communication.

The chromosome constituents of 101 normal mammary gland cells, 122 hyperplastic alveolar nodule (HAN) cells, and 360 cells from eleven 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in the WF rat were examined. Both mammary gland and HAN had normal diploid karyotype patterns, whereas mammary tumors showed frequent (approximately 30%) abnormalities, e.g., aneuploidy, pseudodiploidy, polyploidy, and structural aberrations such as breakage and translocation. These results suggested that chromosome constituents of HAN cells are essentially the same as those of the normal mammary epithelial cells.

Animals↗

PubMed1986

Induction of C-type metaphases and aneuploidy in cultures of V79 cells exposed to extract of automobile exhaust particulates.

An extract of particulate matter (EPM) from gasoline engine exhaust has been tested for its effect on cell viability and plating efficiency, and its ability to produce abnormal mitotic figures and numerical chromosome alterations using the Chinese hamster cell line V79. Within a defined concentration range of EPM (0.62-4.95 micrograms/ml), no significant loss of cell viability could be observed, whereas a strong dose-dependent reduction of plating efficiency occurred. This effect is attributed to the spindle-modifying ability of EPM as could be demonstrated by the induction of C-metaphases and a highly increased mitotic index. As a result of disturbances of the spindle apparatus, EPM was found to induce aneuploidy and polyploidy in a dose-dependent manner.

Aneuploidy↗

PubMed1995

Variation of mouse oocyte sensitivity to griseofulvin-induced aneuploidy during the second meiotic division.

The effects of griseofulvin (GF) treatment during the second meiotic division of oogenesis were investigated by cytogenetic analysis of mouse one-cell (1-Cl) zygotes. After determining the duration of fertilization and the second meiotic division, 1500 mg/kg GF were administered to superovulated mice at 10, 12 or 14 h after human chorionic gonadotrophin (HCG) injection. The results showed that GF reduced the frequencies of fertilized oocytes (P < 0.01) and of 1-Cl zygotes that reached the first mitotic metaphase stage (P < 0.001). Aneuploidy was induced regardless of the moment of treatment, but the various treatment times were associated with statistically different (P < 0.05) levels of hyperdiploidy. The maximum frequency of hyperdiploidy (39.6%) occurred when GF was given 10 h after HCG. Polyploid 1-Cl zygotes were significantly induced only at the 10 and 12 h treatment times and their level never exceeded 1.8% of fertilized oocytes. GF also induced abnormalities of chromosome condensation along with centromeric chromosome associations. These results support the conclusion that GF treatment during the second meiotic division induced aneuploidy, polyploidy, and reduced rates of fertilization and zygotic development. Also, the time of chemical treatment influenced the frequencies of these effects.

Aneuploidy↗

PubMed2001

The preparation of anthraquinone used in the National Toxicology Program cancer bioassay was contaminated with the mutagen 9-nitroanthracene.

Commercial anthraquinone (AQ) (9,10-anthracenedione) is produced by at least three different production methods worldwide: oxidation of anthracene (AQ-OX), Friedel-Crafts technology (AQ-FC) and by Diels-Alder chemistry (AQ-DA), with the final product varying in color and purity. AQ-OX begins with anthracene produced from coal tar and different lots can contain various contaminants, particularly the mutagenic isomers of nitroanthracene. AQ has been reported to be negative in a variety of genotoxicity tests including numerous Ames Salmonella mutagenicity assays. In addition, we report that AQ-DA is negative in the Salmonella-Escherichia coli reverse mutation assays, the L5178Y mouse lymphoma forward mutation assay, for inducing chromosomal aberrations, polyploidy or endoreduplication in Chinese hamster ovary cells, and in the in vivo mouse micronucleus assay. Further, a previous 18 month bioassay conducted with AQ administered to male and female B6C3F(1) and (C57BL/6xAKR)F(1) mice reported no induction of cancer. Thus, it was somewhat unexpected that in a long-term study conducted by the National Toxicology Program (NTP) AQ-OX induced a weak to modest increase in tumors in the kidney and bladder of male and female F344/N rats and a strong increase in the livers of male and female B6C3F(1) mice. In the studies reported here, a sample of the AQ-OX used in the NTP bioassay was shown to be mutagenic in the Ames tester strains TA98, TA100 and TA1537. Addition of an S9 metabolic activation system decreased or eliminated the mutagenic activity. In contrast, the purified NTP AQ-OX as well as the technical grade samples AQ-FC and AQ-DA were not mutagenic in the Ames test. The chemical structure of AQ does not suggest that the parent compound would be DNA reactive. Therefore, a mutagenic contaminant was present in the NTP bioassay sample that is either directly mutagenic or can be activated by bacterial metabolism. Analytical studies showed that the primary contaminant 9-nitroanthracene (9-NA) was present in the NTP AQ-OX at a concentration of 1200 p.p.m., but not in the purified material. The 9-NA and any other contaminants that might have been present in the NTP AQ-OX induced measurable mutagenicity at 9-NA concentrations as low as 0.15 microg/plate in tester strain TA98, indicating potent mutagenic activity. On the basis of revertants per microgram, 9-NA was more potent than benzo[a]pyrene (B[a]P) and was about equally as potent as the 2-nitrofluorene run concurrently as positive controls. TD(50) quantitative carcinogenicity potency estimates indicate that a carcinogen of a potency in the range between B[a]P and dimethylnitrosamine would be required to produce the observed carcinogenic response at the levels of the contaminants found in the test sample. While recognizing that there are limitations in extrapolating mutagenic potency to potential carcinogenic potency, these estimates do indicate that it is plausible that the 9-NA contaminant might have been responsible for all of the tumor induction observed in the NTP study. In fact, in the absence of reliable cancer data, the genetic toxicology profile indicates that AQ would not be a genotoxic carcinogen. Thus, no conclusion as to the carcinogenic activity of AQ can be made at this time.

Animals↗

PubMed2002

Influence of donor age on vinblastine-induced chromosome malsegregation in cultured peripheral lymphocytes.

The incidence of spontaneous aneuploidy in human somatic and germ cells is known to be positively associated with aging. However, the influence of age on the individual susceptibility to chemically induced chromosome malsegregation has not been elucidated. In this study the spindle poison vinblastine (VBL) was used as a model compound to assess the influence of donor age on chemically induced chromosome malsegregation in cultured lymphocytes. Blood cultures from 20 female donors belonging to two different age groups (10 <30 years and 10 >50 years) were treated with VBL (7.5 ng/ml) from 43 h after mitogen stimulation until harvest at 60 h, i.e. during the time interval corresponding to G2/M. In order to block cytokinesis, cytochalasin B (6 microg/ml) was added to cultures at 44 h. For each donor the incidence of micronuclei, polyploidy and malsegregation (non-disjunction and loss) of chromosomes X and 8 was determined using fluorescence in situ hybridization with chromosome-specific centromeric probes. Both background incidence of micronuclei and spontaneous chromosome X non-disjunction were significantly elevated in older donors. Individual responses to VBL treatment showed wide interindividual variability, which was not significantly associated with the age of the donor. In both age classes chromosome X was more susceptible than chromosome 8 to both spontaneous and VBL-induced malsegregation. These results indicate that donor age has a limited influence on the aneugenic effects exerted by VBL in peripheral lymphocytes in vitro. Other factors have to be considered to account for the large interindividual variation in sensitivity to VBL challenge observed in this work.

Adult↗