Showing papers on "Sister chromatid exchange published in 2010"
TL;DR: Although DHJs are identified as intermediates of DSB-promoted recombination in both mitotic and meiotic cells, their formation is distinctly regulated according to the specific dictates of the two cellular programs.
Abstract: Repair of DNA double-strand breaks (DSBs) by homologous recombination is crucial for cell proliferation and tumour suppression. However, despite its importance, the molecular intermediates of mitotic DSB repair remain undefined. The double Holliday junction (DHJ), presupposed to be the central intermediate for more than 25 years, has only been identified during meiotic recombination. Moreover, evidence has accumulated for alternative, DHJ-independent mechanisms, raising the possibility that DHJs are not formed during DSB repair in mitotically cycling cells. Here we identify intermediates of DSB repair by using a budding-yeast assay system designed to mimic physiological DSB repair. This system uses diploid cells and provides the possibility for allelic recombination either between sister chromatids or between homologues, as well as direct comparison with meiotic recombination at the same locus. In mitotically cycling cells, we detect inter-homologue joint molecule (JM) intermediates whose strand composition and size are identical to those of the canonical DHJ structures observed in meiosis. However, in contrast to meiosis, JMs between sister chromatids form in preference to those between homologues. Moreover, JMs seem to represent a minor pathway of DSB repair in mitotic cells, being detected at about tenfold lower levels (per DSB) than during meiotic recombination. Thus, although DHJs are identified as intermediates of DSB-promoted recombination in both mitotic and meiotic cells, their formation is distinctly regulated according to the specific dictates of the two cellular programs.
226 citations
TL;DR: Overall, PAs are mutagenic in vivo and in vitro and their mutagenicity appears to be responsible for the carcinogenesis of PAs.
Abstract: Pyrrolizidine alkaloids (PAs) are common constituents of many plant species around the world. PA-containing plants are probably the most common poisonous plants affecting livestock and wildlife. They can inflict harm to humans through contaminated food sources, herbal medicines and dietary supplements. Half of the identified PAs are genotoxic and many of them are tumorigenic. The mutagenicity of PAs has been extensively studied in different biological systems. Upon metabolic activation, PAs produce DNA adducts, DNA cross-linking, DNA breaks, sister chromatid exchange, micronuclei, chromosomal aberrations, gene mutations and chromosome mutations in vivo and in vitro. PAs induced mutations in the cII gene of rat liver and in the p53 and K-ras genes of mouse liver tumors. It has been suggested that all PAs produce a set of (+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine-derived DNA adducts and similar types of gene mutations. The signature types of mutations are G : C --> T : A transversion and tandem base substitutions. Overall, PAs are mutagenic in vivo and in vitro and their mutagenicity appears to be responsible for the carcinogenesis of PAs.
167 citations
TL;DR: It is demonstrated that depletion of the evolutionarily conserved minichromosome maintenance helicase-binding protein ETG1 of Arabidopsis thaliana resulted in a stringent late G2 cell cycle arrest and that cohesion establishment is essential for proper development of plants suffering from endogenous DNA stress.
Abstract: The DNA replication process represents a source of DNA stress that causes potentially spontaneous genome damage. This effect might be strengthened by mutations in crucial replication factors, requiring the activation of DNA damage checkpoints to enable DNA repair before anaphase onset. Here, we demonstrate that depletion of the evolutionarily conserved minichromosome maintenance helicase-binding protein ETG1 of Arabidopsis thaliana resulted in a stringent late G2 cell cycle arrest. This arrest correlated with a partial loss of sister chromatid cohesion. The lack-of-cohesion phenotype was intensified in plants without functional CTF18, a replication fork factor needed for cohesion establishment. The synergistic effect of the etg1 and ctf18 mutants on sister chromatid cohesion strengthened the impact on plant growth of the replication stress caused by ETG1 deficiency because of inefficient DNA repair. We conclude that the ETG1 replication factor is required for efficient cohesion and that cohesion establishment is essential for proper development of plants suffering from endogenous DNA stress. Cohesion defects observed upon knockdown of its human counterpart suggest an equally important developmental role for the orthologous mammalian ETG1 protein.
65 citations
TL;DR: The current models for establishment of S-phase and DI-cohesion in the context of their involvement in DSB repair are presented and discussed.
62 citations
TL;DR: It is shown that even transient inhibition of ATM kinase for 1 hour, initiated 15 minutes after cellular irradiation, resulted in an accumulation of persistent chromosome aberrations and increased cell death, which suggests that A-T fibroblasts have adapted to the loss of ATM and have alternative mechanisms to initiate SCE.
Abstract: Cells derived from ataxia telangiectasia (A-T) patients exhibit defective cell cycle checkpoints because of mutations in the gene encoding ATM (ataxia telangiectasia mutated). After exposure to ionizing radiation (IR), A-T cells exhibit sensitivity to IR-induced cellular damage that results in increased chromosome aberrations and cell death (radiosensitivity). ATM is a member of a family of kinases that become activated in response to DNA damage. We showed that even transient inhibition of ATM kinase for 1 hour, initiated 15 minutes after cellular irradiation, resulted in an accumulation of persistent chromosome aberrations and increased cell death. Using reversible inhibitors of DNA-PK (DNA-dependent protein kinase), another kinase involved in responding to DNA damage, and ATM, we showed that these two kinases acted through distinct DNA repair mechanisms: ATM resolved DNA damage through a mechanism involving sister chromatid exchange (SCE), whereas DNA-PK acted through nonhomologous end joining. Furthermore, because DNA damage–induced SCE occurred in A-T fibroblasts that lack functional ATM protein, and the inhibitors of ATM kinase had no effect on DNA damage–induced SCE in A-T fibroblasts, we showed that the consequences of short-term inhibition of the kinase activity of ATM and adaptation to ATM protein disruption were distinct. This suggests that A-T fibroblasts have adapted to the loss of ATM and have alternative mechanisms to initiate SCE.
61 citations
TL;DR: It is suggested for the first time that boric acid can prevent the genotoxicity of PAC on human lymphocytes and cytotoxicity indices were diminished by the addition of BA.
Abstract: Paclitaxel (PAC) is an anticancer drug used for treatments of breast, ovarian and lung cancers. However, little data is available in the literature on its potential genotoxicity on healthy human cells. On the other hand, boron deficiency and supplementation exert important biological effects in human and animal tissues. The biological effects of dietary boron are defined, but its interaction with PAC is not known for therapeutic uses. The aim of the present study was to determine whether boric acid (BA) confer a protection against PAC genotoxicity. After the application of PAC (10 or 20 μg/l) and BA (2.5 or 5 mg/l), the genotoxic effects were assessed by sister chromatid exchange (SCE) and micronucleus (MN) tests in human blood cultures. We also analyzed nuclear division index (NDI) in peripheral lymphocytes. Our results showed that PAC significantly (P < 0.05) increased the frequencies of SCEs and the formations of MNs in peripheral lymphocytes as compared to controls. PAC decreased the nuclear division index in lymphocyte cultures. Boric acid did not show cytotoxic or genotoxic effects at the concentrations tested. Furthermore, the PAC-induced increases in the genotoxicity and cytotoxicity indices were diminished by the addition of BA. The present study suggests for the first time that BA can prevent the genotoxicity of PAC on human lymphocytes.
61 citations
TL;DR: During meiosis, the template for homologous recombination is not chosen at random as described in this Primer by Jessica Lao and Neil Hunter.
Abstract: Connections between chromosomes are essential for theiraccurate segregation during cell division. In somatic cells dividingby mitosis, newly replicated sister chromatids are connected bycohesin proteins. When the sister chromatids become attached tomicrotubules emanating from opposite poles of the spindle,cohesins resist the pulling forces and the ensuing tension stabilizesthe chromatid–microtubule attachments. In this way, each pair ofsister chromatids achieves a stable bipolar attachment to thespindle. Consequently, when cohesion is destroyed at the onset ofanaphase, sister chromatids are pulled to opposite poles and eachnew cell receives a full complement of maternal and paternalchromosomes.In the germline, meiosis employs two successive rounds ofnuclear division to produce gametes containing half the number ofchromosomes as the original precursor cell. During the firstdivision, sister chromatids remain connected while the paternaland maternal homologs are segregated (one homolog comprises apair of sister chromatids). Homolog segregation during meiosis isgoverned by the same mechanical principles as sister segregationduring mitosis and, as such, homologs must be connected. Theseconnections are called chiasmata, and they are established via aprocess called homologous recombination, a DNA repair processthat involves interaction between a broken chromosome and ahomologous template chromosome.To ensure that each pair of homologs is connected by at leastone chiasma, homologous recombination during meiosis isregulated at several levels. A key aspect of this regulation is thechoice of recombination template. The sister chromatid is thepreferred template for recombinational repair in cells dividing bymitosis. However, during meiosis this bias must be overcome sothat homologs recombine and become connected by chiasmata.How template choice is regulated remains unclear, but studies ofmeiotic recombination in budding yeast have suggested a numberof possible mechanisms.
59 citations
TL;DR: It is demonstrated that pirimicarb and Aficida exert geno-cytotoxicity, at least in CHO-K1 cells, and the CAs appears to be a higher sensitive bioassay to detect DNA damage at lower concentrations of pirimiarb than SCEs does.
44 citations
TL;DR: A hypothesis is advanced proposing transient inhibition of DSB processing by Hop1 and Mek1 and thus providing more time for repair by interaction with the homologous chromosome, as well as enhancing homolog interactions to ensure wild-type level of crossover formation rather than inhibiting sister chromatid interactions.
Abstract: Synaptonemal complex (SC) proteins Hop1 and Mek1 have been proposed to promote homologous recombination in meiosis of Saccharomyces cerevisiae by establishment of a barrier against sister chromatid recombination. Therefore, it is interesting to know whether the homologous proteins play a similar role in Schizosaccharomyces pombe. Unequal sister chromatid recombination (USCR) was found to be increased in hop1 and mek1 single and double deletion mutants in assays for intrachromosomal recombination (ICR). Meiotic intergenic (crossover) and intragenic (conversion) recombination between homologous chromosomes was reduced. Double-strand break (DSB) levels were also lowered. Notably, deletion of hop1 restored DSB repair in rad50S meiosis. This may indicate altered DSB repair kinetics in hop1 and mek1 deletion strains. A hypothesis is advanced proposing transient inhibition of DSB processing by Hop1 and Mek1 and thus providing more time for repair by interaction with the homologous chromosome. Loss of Hop1 and Mek1 would then result in faster repair and more interaction with the sister chromatid. Thus, in S. pombe meiosis, where an excess of sister Holliday junction over homologous Holliday junction formation has been demonstrated, Hop1 and Mek1 possibly enhance homolog interactions to ensure wild-type level of crossover formation rather than inhibiting sister chromatid interactions.
43 citations
TL;DR: The behavior of sister centromeres in univalents in wheat is examined, showing that by metaphase I they often lose their coordination, leading to stable bipolar attachment and frequent separation of sister chromatids or to misdivision.
Abstract: Centromeres are responsible for the proper behavior of chromosomes in cell divisions. In meiosis the process is more complicated than in mitosis, as each chromosome in a bivalent has 2 sister centromeres and their behavior has to be strictly coordinated. Here, the behavior of sister centromeres in univalents in wheat is examined, showing that by metaphase I they often lose their coordination. This loss accelerates with the progression of anaphase I, leading to stable bipolar attachment and frequent separation of sister chromatids or to misdivision. Depending on the orientation of a univalent and its sister centromeres, misdivision may occur across the centromere region or across the pericentric chromatin. Chromosome fragments consisting of only the centromere region did not survive to the next generation. Midget chromosomes composed of the centromeres and parts of the pericentric chromatin did survive, but their transmission rates were low and appeared related to the amount of pericentric chromatin, probably because only the pericentric chromatin provides sister chromatid cohesion. As the cohesion of sister chromatids appears to be a function of the proximity to the kinetochore region, the definition of the centromere need not include pericentric regions.
42 citations
TL;DR: The results clearly indicate towards the protection of lymphocytes from toxic effects af As and F by melatonin in vitro, and this work confirms melatonin as an effective anti-oxidant and anti-genotoxic substance.
TL;DR: Results imply that adequate expression of Rad51C in mammalian cells is essential for maintaining genomic stability and sister chromatid cohesion to prevent malignant transformation.
Abstract: Homologous recombination is essential for repair of DNA interstrand cross-links and double-strand breaks. The Rad51C protein is one of the five Rad51 paralogs in vertebrates implicated in homologous recombination. A previously described hamster cell mutant defective in Rad51C (CL-V4B) showed increased sensitivity to DNA damaging agents and displayed genomic instability. Here, we identified a splice donor mutation at position +5 of intron 5 of the Rad51C gene in this mutant, and generated mice harboring an analogous base pair alteration. Rad51Csplice heterozygous animals are viable and do not display any phenotypic abnormalities, however homozygous Rad51Csplice embryos die during early development (E8.5). Detailed analysis of two CL-V4B revertants, V4B-MR1 and V4B-MR2, that have reduced levels of full-length Rad51C transcript when compared to wild type hamster cells, showed increased sensitivity to mitomycin C (MMC) in clonogenic survival, suggesting haploinsufficiency of Rad51C. Similarly, mouse Rad51Csplice/neo heterozygous ES cells also displayed increased MMC sensitivity. Moreover, in both hamster revertants, Rad51C haploinsufficiency gives rise to increased frequencies of spontaneous and MMC-induced chromosomal aberrations, impaired sister chromatid cohesion and reduced cloning efficiency. These results imply that adequate expression of Rad51C in mammalian cells is essential for maintaining genomic stability and sister chromatid cohesion to prevent malignant transformation.
TL;DR: It is shown that Blm has roles both upstream and downstream of the Rad54 protein, a core HR factor, and the data are consistent with Blm having at least two roles in HR repair in mammalian cells.
Abstract: BLM is a RecQ family helicase that is defective in individuals with the cancer predisposition disorder, Bloom's syndrome (BS). At the cellular level, BS is characterized by hyper-recombination manifested as excessive sister chromatid exchange and loss of heterozygosity. However, the precise function of BLM remains unclear. Multiple roles have been proposed for BLM in the homologous recombination (HR) repair pathway, including 'early' functions, such as the stimulation of resection of DNA double-strand break ends or displacement of the invading strand of DNA displacement loops, and 'late' roles, such as dissolution of double Holliday junctions. However, most of the evidence for these putative roles comes from in vitro biochemical data. In this study, we report the characterization of mouse embryonic stem cells with disruption of Blm and/or Rad54 genes. We show that Blm has roles both upstream and downstream of the Rad54 protein, a core HR factor. Disruption of Rad54 in the Blm-mutant background reduced the elevated level of gene targeting and of sister chromatid exchanges, implying that Blm primarily functions downstream of Rad54 in the HR pathway. Conversely, however, mutation of Blm in Rad54(-/-) cells rescued their mitomycin C (MMC) sensitivity, and decreased both the level of DNA damage and cell cycle perturbation induced by MMC, suggesting an early role for Blm. Our data are consistent with Blm having at least two roles in HR repair in mammalian cells.
TL;DR: A novel mechanism of genomic instability and malignant progression in esophageal cancers, a deadly disease of increasing incidence in developed countries is reported.
Abstract: Amplification of 19q is a frequent genetic alteration in many solid tumors, and SEI1 is a candidate oncogene within the amplified region Our previous study found that the oncogenic function of SEI1 was associated with chromosome instability In this study, we report a novel mechanism of genomic instability involving the SEI1-SET-NM23H1 pathway Overexpression of SEI1 was observed in 57 of 100 of esophageal squamous cell carcinoma cases Functional study showed that SEI1 had strong tumorigenic ability, and overexpression of SEI1 could induce the genomic instability by increasing micronuclei formation and reducing the number of chromosomes Further study found that SEI1 was able to upregulate SET expression and subsequently promote the translocation of a small amount of NM23H1 from the cytoplasm to the nucleus Nuclear NM23H1 can induce DNA damage through its DNA nick activity Unlike CTL attack, only a small amount of NM23H1 translocated into the nucleus (<10%) induced by the overexpression of SEI1 Further study found that the small amount of NM23H1 only induced minor DNA damage and subsequently increased genomic instability, rather than inducing irreparable DNA damage and initiating apoptosis by CTL attack Sister chromatid exchange experiment found that the translocation of small amount of NM23H1 into the nucleus induced by the overexpressions of SEI1/SET could increase the frequency of sister chromatid exchange In addition, overexpression of SEI1 was associated with poor prognosis of esophageal squamous cell carcinoma Taken together, these findings define a novel mechanism of genomic instability and malignant progression in esophageal cancers, a deadly disease of increasing incidence in developed countries
TL;DR: The results showed that low-level chronic occupational exposure to ionizing radiation causes an increase of MN frequency in chromosomes, even though the absorbed doses were below the permissible limits.
Abstract: Ionizing radiation is known to induce mutations and cell transformations, predominantly by causing single-strand and double-strand DNA breakage, thereby leading to chromosome instability and carcinogenesis. The aim of this study was to evaluate genotoxic effects in hospital staff exposed to low-dose ionizing radiation in comparison with a selected control group, by using the cytokinesis-blocked micronucleus (CBMN) and sister chromatid exchange (SCE) tests in peripheral blood lymphocytes. The study included 40 exposed radiology staff and 30 control subjects. The frequency of micronuclei (MN) was significantly increased in radiation-exposed groups compared with control persons (p < 0.05). The frequency of SCE did not show any significant difference in the exposed individuals in comparison to the controls. Our results showed that low-level chronic occupational exposure to ionizing radiation causes an increase of MN frequency in chromosomes, even though the absorbed doses were below the permissible limits. Our studies indicate that the CBMN assay is considered to be sensitive test in contrast to SCE analysis to evaluate chromosomal damage induced by ionizing radiation.
TL;DR: The data indicate that Fancc deficiency accelerates telomere shortening during high turnover of hematopoietic cells and promotes telitere recombination initiated by short telomeres.
Abstract: Telomere shortening has been linked to rare human disorders that present with bone marrow failure including Fanconi anemia (FA). FANCC is one of the most commonly mutated FA genes in FA patients and the FANCC subtype tends to have a relatively early onset of bone marrow failure and hematologic malignancies. Here, we studied the role of Fancc in telomere length regulation in mice. Deletion of Fancc (Fancc−/−) did not affect telomerase activity, telomere length or telomeric end-capping in a mouse strain possessing intrinsically long telomeres. However, ablation of Fancc did exacerbate telomere attrition when murine bone marrow cells experienced high cell turnover after serial transplantation. When Fancc−/− mice were crossed into a telomerase reverse transcriptase heterozygous or null background (Tert+/− or Tert−/−) with short telomeres, Fancc deficiency led to an increase in the incidence of telomere sister chromatid exchange. In contrast, these phenotypes were not observed in Tert mutant mice with long telomeres. Our data indicate that Fancc deficiency accelerates telomere shortening during high turnover of hematopoietic cells and promotes telomere recombination initiated by short telomeres.
TL;DR: Hemidesmus indicus root extract possesses significant genoprotective effect at the lower concentrations although it is cytotoxic and probably genotoxic at higher doses.
TL;DR: This study shows that the two classes of anti-establishment complexes are indistinguishable when challenged both genetically and functionally, and suggests that both classes function in a singular pathway that is centered on CTF7/Eco1 (herein termed Ctf7) regulation.
Abstract: Recent studies have lead to a rapid expansion of sister chromatid cohesion pathways. Of particular interest is the growth in classifications of anti-establishment factors—now including those that are cohesin-associated (Rad61/WAPL and Pds5) or DNA replication fork-associated (Elg1-RFC). In this study, we show that the two classes of anti-establishment complexes are indistinguishable when challenged both genetically and functionally. These findings suggest that both classes function in a singular pathway that is centered on Ctf7/Eco1 (herein termed Ctf7) regulation. The anti-establishment activity of Elg1-RFC complex is particular intriguing given that an alternate Ctf18-RFC complex exhibits robust pro-establishment activity. Here, we provide several lines of evidence, including the use of Ctf7 bypass suppressors, indicating that these activities are not simply antagonistic. Moreover, the results suggest that Ctf18-RFC is capable of promoting sister chromatid pairing reactions independent of Ctf7. The combination of these studies suggest a new model of sister chromatid pairing regulation.
TL;DR: Data showed a significant inhibitory effect of GJ against the chromosome damage induced by the tested agent, suggesting the relevance of carrying out studies to clarify the involved mechanism of action as well as to determine the cancer chemopreventive capacity of the juice.
Abstract: The consumption of grapefruit juice (GJ) has been associated with various activities potentially beneficial for human health, including protection against the DNA damage produced by various compounds. In the present report, we evaluated the capability of this juice to inhibit the rate of micronucleated polychromatic erythrocytes (MNPE) and sister chromatid exchanges (SCE) induced by the antineoplastic alkylating agent ifosfamide (IF). We tested the effect of administering 100, 500, and 1000 mg/kg of GJ in mouse and obtained the following results: a) with the high dose, a reduction of 72% in the rate of SCE induced by IF; b) a mean reduction of 65.3% in the rate of MNPE compared with the damage induced by IF at 48 h post-administration; c) no modification induced by GJ either on the cellular proliferation kinetics or in the mitotic index; and d) neither induction of bone marrow cytotoxicity by GJ nor a protective effect of the juice against the cytotoxicity induced by IF. These data showed a significant inhibitory effect of GJ against the chromosome damage induced by the tested agent; they also suggest the relevance of carrying out studies to clarify the involved mechanism of action as well as to determine the cancer chemopreventive capacity of the juice.
Journal Article•
TL;DR: The genotoxic and antigenotoxic effects of Aloe vera leaf extract were investigated using the chromosome aberrations (CAs) test for the bone marrow cells of rats, sister chromatid exchanges (SCEs) and micronucleus (MN) and CAs tests for human lymphocytes, and the Ames Salmonella/microsome test system.
Abstract: The genotoxic and antigenotoxic effects of Aloe vera leaf extract (AV) were investigated using the chromosome aberrations (CAs) test for the bone marrow cells of rats, sister chromatid exchanges (SCEs) and micronucleus (MN) and CAs tests for human lymphocytes, and the Ames Salmonella/microsome test system. In the bone marrow cells of rats, AV extract significantly induced structural and total CAs at all concentrations and in all treatment periods. In human peripheral lymphocytes, AV did not increase the mean SCE; however, it significantly induced the MN frequency and structural CAs. In addition, AV showed a cytotoxic effect by decreasing the replication index (RI), mitotic index (MI), and nuclear division index (NDI) in human lymphocytes and by decreasing the MI in the bone marrow cells of rats. AV did not decrease the genotoxicity or cytotoxicity of urethane (ethyl carbamate, EC) in the bone marrow cells of rats or in the mitomycin-C (MMC) in human lymphocytes. AV was a weak mutagen in the TA98 strain of Salmonella typhimurium in the absence of S9mix; however, AV+NPD (4-nitro-o-phenylenediamine) and AV+SA (sodium azide) exhibited a synergism in increasing the number of revertants for the TA98 and TA100 strains in the absence of S9mix, respectively.
TL;DR: The anti-epileptic drugs given to epileptic women in mono- and poly-therapy during pregnancy evoked potentially clastogenic and genotoxic effects in cord-blood lymphocytes of the newborns whose mothers received long-term AEDs therapy during pregnancy.
Abstract: Epidemiological data indicate that pregnancies of epileptic women constitute about 1% of all pregnancies. Newborns of mothers exposed to anti-epileptic drugs (AEDs) are at increased risk for major congenital malformations, cognitive impairment and fetal death. Cord-blood lymphocytes of the newborns whose mothers received long-term AEDs therapy during pregnancy were used in this study. There were 37 newborns (Group A), divided into two subgroups, i.e. from mothers receiving mono-therapy (A1) and from those receiving poly-therapy (A2). The major drugs given to the pregnant women with epilepsy in mono-therapy were valproic acid (VPA) and carbamazepine (CBZ) analogues. In poly-therapy, besides VPA and CBZ derivatives also phenyltriazine, sulphanamide, benzodiazepines and gamma-aminobutyric acid (GABA) derivatives were administered. Three kinds of in vitro cytogenetic test were applied: the chromosome aberration (CA) assay, the sister chromatid exchange (SCE) assay, and the cytokinesis-block micronucleus assay (CBMN). In addition, the mitotic index (MI), the replication index (RI) and the nuclear division index (NDI) were determined. The mean number of CA/cell (excluding gaps) for group A did not differ statistically significantly from the negative controls (p>0.1), nor did the mean MI value (p>0.1). In group A, the mean number of SCE/cell was statistically significantly higher compared with the negative control (p 0.1). The mean MN number for group A was higher than in the negative control, but this difference was on the border of statistical significance (p=0.07). The value of NDI for group A did not differ significantly from the value in the negative control (p>0.1). The anti-epileptic drugs given to epileptic women in mono- and poly-therapy during pregnancy evoked potentially clastogenic and genotoxic effects in cord-blood lymphocytes. These drugs did not exert a cytotoxic effect, neither did they inhibit the cell-division kinetics of cord-blood lymphocytes.
TL;DR: Different PCB metabolites may induce carcinogenesis by different mechanisms, including SCE induction or polyploidization, and the finding that up to 96% of metaphases from cells treated with PCB2- or PCB3-HQ were tetraploid was surprising, some of which had dark and some Harlequin-stained chromosomes.
TL;DR: In this article, the safety of aspartame and its metabolic breakdown products (phenylalanine, aspartic acid and methanol) was investigated in vivo using chromosomal aberration (CA) test and sister chromatid exchange (SCE) test in the bone marrow cells of mice.
Abstract: Aspartame (a-Laspartyl-L-phenylalanine 1-methylester) is a dipeptide low-calorie artificial sweetener that is widely used as a nonnutritive sweetener in foods and drinks. The safety of aspartame and its metabolic breakdown products (phenylalanine, aspartic acid and methanol) was investigated in vivo using chromosomal aberration (CA) test and sister chromatid exchange (SCE) test in the bone marrow cells of mice. Swiss Albino male mice were exposed to aspartame (3.5, 35, 350 mg/kg body weight). Bone marrow cells isolated from femora were analyzed for chromosome aberrations and sister chromatid exchanges. Treatment with aspartame induced dose dependently chromosome aberrations at all concentrations while it did not induce sister chromatid exchanges. On the other hand, aspartame did not decrease the mitotic index (MI). However, statistical analysis of the results show that aspartame is not significantly genotoxic at low concentration.
TL;DR: Three recent studies reveal unexpected functions of Rap1, a member of the shelterin complex that protects chromosome ends from the activity of DNA repair pathways, which functions in genome-wide transcriptional regulation and NF-κB-dependent signalling.
Abstract: Three recent studies reveal unexpected functions of Rap1, a member of the shelterin complex that protects chromosome ends from the activity of DNA repair pathways. Rap1 not only protects telomeres from sister chromatid exchange, but also functions in genome-wide transcriptional regulation and NF-κB-dependent signalling, revealing new perspectives for the telomere field.
TL;DR: Investigation of cytogenetic damage and DNA repair functions in human peripheral lymphocytes exposed to hypoxia by means of sister chromatid exchange and nuclear and mitochondrial microsatellite instability revealed gradual increases in SCE for both exposure times, compared to the controls, but there was no significant correlation between Hypoxia and MSI.
TL;DR: Erythropoietin acts protectively against the genotoxic potential of MMC, and this action may have clinical implications.
Abstract: Background: Erythropoietin (EPO) is a glycoprotein which has a main property, erythropoiesis, but its range of action in the human body is very wide. It has been suggested that EPO
TL;DR: A significant increase in the SCE frequencies along with a significant reduction in mitotic indices was observed in patients with CRF compared with the controls, and these results could also be of a great importance in early diagnosis to prognosticate a possible generation of neoplasm in the future.
Abstract: Objective: The aim of this study was to investigate the frequency of sister chromatid exchanges (SCEs), the presence of cytostaticity, cytotoxicity, and therefore, the possible genetic instability in patients with chronic renal failure (CRF) in human cultured peripheral blood lymphocytes. Methods: Peripheral blood lymphocytes were cultured from 32 patients with CRF (average 55.2 years) and 18 healthy blood donors (average 44.6 years), and the SCE method was applied afterward. The increase in SCE frequency was evaluated as an immediate DNA damage index, while the reduction in the values of the proliferating rate indices was evaluated as a cytostatic index and the mitotic indices as a cytotoxic index was also measured. Results: A significant increase in the SCE frequencies along with a significant reduction in mitotic indices was observed in patients with CRF compared with the controls. It is notable that there was no significant difference in SCE levels among patients with CRF and cancer, and patients with...
Journal Article•
TL;DR: The results suggest that exposure of high Cd concentrations is cytotoxic as well as genotoxic for Vicia faba L. and also suggest that the 2 phenomena are related.
Abstract: The effects of cadmium (Cd) on antioxidant responses and sister chromatid exchanges (SCE) were studied in Vicia faba L. The activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR), and the levels of ascorbate (ASC), glutathione (GSH), hydrogen peroxide, and malondialdehyde (MDA, indicator of lipid peroxidation) were measured. Genotoxicity was evaluated by measuring the changes in the mitotic index (MI) and sister chromatid exchanges (SCE). Increased activities of SOD and CAT were observed in plants treated with 50 and 100 μM Cd. It was found that APX activity increased remarkably with 50 μM Cd, but no significant changes were found in GR activity in any of the treatment groups. These changes in antioxidant enzyme activities were negatively correlated with lipid peroxidation. However, a positive correlation between the increase of H2O2 levels and Cd concentration occurred with all levels of Cd. A significant increase in the malondialdehyde (MDA) level was only observed at the highest (200 μM) Cd concentration. This finding suggests that membrane damage did not occur in moderate Cd frequency. SCE increased significantly in high Cd concentration (200 μM), while MI decreased. The results suggest that exposure of high Cd concentrations is cytotoxic as well as genotoxic for Vicia faba L. and also suggest that the 2 phenomena are related.
TL;DR: It is possible that the radioprotective action of ascorbic acid would be effective in non-complex type DNA damage such as induced by X-rays, as well as after heavy ion exposure such as to carbon ions.
Abstract: We studied the effects and mechanisms of ascorbic acid as a radiation protector. Cell survival, repair of DNA double strand breaks (DSBs), and sister chromatid exchanges (SCEs) were examined in normal human fibroblasts irradiated with X-rays and heavy ions. Post-irradiation treatment with 5mM ascorbic acid for 24 h in plateau phase (non-cycling) cells enhanced cell survival and DNA double strand break repair, and reduced SCEs after X-rays irradiation. On the other hand, only reduced SCEs were observed after heavy ion exposure such as to carbon ions. Judging from our data, it is possible that the radioprotective action of ascorbic acid would be effective in non-complex type DNA damage such as induced by X-rays. These findings provide new insight into the mechanism of DNA damage and repair produced by heavy ion irradiation.
23 Sep 2010
TL;DR: This work strongly suggests that progressive telomere erosion is not the only determinant of replicative capacity; instead, T-SCE need to be considered as an independent factor controlling colony growth and senescence.
Abstract: Telomeres are a hotspot for sister chromatid exchange (T-SCE). Any biological consequence of this form of instability remained obscure until quantitative modeling revealed a link between elevated T-SCE rates and accelerated cellular replicative senescence. This work strongly suggests that progressive telomere erosion is not the only determinant of replicative capacity; instead, T-SCE need to be considered as an independent factor controlling colony growth and senescence. Additionally high T-SCE rates have been observed in cells with deficiencies in WRN and BLM, the genes that are defective in Werner's and Bloom's syndromes, implying a connection to premature aging. In this Research Perspective we will explore some of the implications this recent work has for human health.