Showing papers on "Sister chromatid exchange published in 2018"
TL;DR: It is demonstrated that ATRX-deficient cells exhibit a defect in repairing exogenously induced DNA double-strand breaks (DSBs) by HR, which suggests that AtRX facilitates the chromatin reconstitution required for extended DNA repair synthesis and sister chromatid exchange during HR.
90 citations
TL;DR: The investigated concentrations of escitalopram and doxepin were non-cytotoxic but potentially genotoxic at higher concentrations, suggesting that these drugs might have genot Toxic, carcinogenic, and mutagenic effects.
Abstract: Antidepressants are drugs used for the treatment of many psychiatric conditions including depression. There are findings suggesting that these drugs might have genotoxic, carcinogenic, and/or mutagenic effects. Therefore, the present in vitro study is intended to investigate potential genotoxic and cytotoxic effects of the antidepressants escitalopram (selective serotonin reuptake inhibitor) and doxepin (Tricyclic antidepressant) on human peripheral lymphocytes cytokinesis-block micronucleus (CBMN), sister chromatid exchange (SCE), and single cell gel electrophoresis (alkaline comet assay) were used for the purpose of the study. In the study, four different concentrations of both drugs (1, 2.5, 5, and 10 µg/mL) were administered to human peripheral lymphocytes for 24 h. The tested concentrations of both drugs were found to exhibit no cytotoxic and mitotic inhibitory effects. SCE increase caused by 5 and 10 µg/mL of escitalopram was found statistically significant, while no statistically significant increase was observed in DNA damage and micronucleus (MN) formation. Moreover, the increase caused by doxepin in MN formation was not found statistically significant. Besides, 10 µg/mL of doxepin was demonstrated to significantly increase arbitrary unit and SCE formation. These findings suggest that the investigated concentrations of escitalopram and doxepin were non-cytotoxic but potentially genotoxic at higher concentrations.
15 citations
05 Apr 2018
TL;DR: The Cen-CO-FISH method revealed that human centromeres indeed undergo recombination in cycling cells resulting in C-SCE, and centromere instability is enhanced in cancer cell lines and primary cells undergoing senescence.
Abstract: Human centromeres are composed of large tandem arrays of repetitive alpha satellite DNA, which are often sites of aberrant rearrangement in cancers ( Mitelman et al., 1997 ; Padilla- Nash et al., 2001 ). To date, annotation of the human centromere repetitive sequences remains incomplete, greatly hindering in-depth functional studies of these regions essential for chromosome segregation. In order to monitor sister chromatid exchange happening at the centromere (C-SCE) due to recombination and mutagenic events, I have applied the Chromosome-Orientation Fluorescence in situ Hybridization (CO-FISH) technique to centromeres (Cen-CO-FISH) in human cells. This hybridization-based method involves (1) the incorporation of nucleotide analogs through a single round of replication, (2) enzymatic digestion of the newly synthesized DNA strand and (3) subsequent hybridization of single-stranded probes, in absence of a denaturation step. The resulting signal allows to differentially label each sister chromatid based on the 5'-3' directionality of the DNA and to score aberrant staining patterns indicative of C-SCE. The Cen-CO-FISH method applied to human centromeres revealed that human centromeres indeed undergo recombination in cycling cells resulting in C-SCE, and centromere instability is enhanced in cancer cell lines and primary cells undergoing senescence (Giunta and Funabiki, 2017). Here, I present the detailed protocol of the preparation, experimental procedure and data acquisition for the Cen-CO-FISH method in human cells. It also includes a conceptual overview of the technique, with examples of representative images and scoring guidelines. The Cen-CO-FISH represents a valuable tool to facilitate exploration of centromere repeats.
15 citations
TL;DR: There is strong evidence that 1,4-NQ does not induce gene mutations in bacteria or mammalian cells in vitro with predominantly negative Ames tests and negative Hprt and tk mutation studies, and evidence indicates that the mechanism of in vitro clastogenicity is predominantly via ROS generation.
Abstract: 1,4-Naphthoquinone (1,4-NQ; CAS RN 130-15-4), a derivative of naphthalene, is a commonly used pre-cursor in industrial processes. Since the early 1980's 1,4-NQ has been tested in a number of genotoxicity assays, both in vitro and in vivo. There is strong evidence that 1,4-NQ does not induce gene mutations in bacteria or mammalian cells in vitro with predominantly negative Ames tests and negative Hprt and tk mutation studies. However, there is clear evidence of a clastogenic response in vitro from positive micronucleus, sister chromatid exchange and chromosome aberration assays. 1,4-NQ-treated mice and hamsters were, however, negative for micronucleus or chromosomal aberration induction in GLP-compliant studies with clear evidence of target tissue exposure, suggesting an in vitro only effect. Evidence indicates that the mechanism of in vitro clastogenicity is predominantly via ROS generation, and since in vitro mammalian cell tests systems have poor anti-oxidant defence mechanisms, they are particularly sensitive to oxidative DNA damage. On the other hand, healthy mammalian tissues have more efficient anti-oxidant defence mechanisms, and therefore it is not surprising that 1,4-NQ is not genotoxic in vivo.
14 citations
TL;DR: Clear evidence is shown that diets rich in Verbascoside (and/or Lycopene) do not originate any mutagenic activity, resulting no cytotoxic for the animals and, suggesting a possible their use in both animal and human diets.
12 citations
TL;DR: The results showed that 4-MEI pose a genotoxic and cytotoxic effects for human peripheral lymphocytes.
Abstract: 4-Methylimidazole (4-MEI), a heterocyclic organic chemical compound, is widely found in many foods and consumed by people worldwide. In this research, we aimed to investigate the cytotoxic and genotoxic effects of 4-MEI on human lymphocytes. For this purpose, human peripheral blood lymphocytes were treated with four concentrations of 4-MEI (300, 450, 600 and 750 μg/ml) for 24 h and 48 h periods and in vitro sister chromatid exchange (SCE), chromosome aberration (CA) and micronucleus (MN) tests were used. 4-MEI induced SCE in human peripheral lymphocytes at three highest concentrations (450, 600 and 750 μg/ml) in 48 h treatment period. CA and MN were induced in human peripheral lymphocytes at two highest concentrations of 4-MEI (600 and 750 μg/ml) in 24 h and 48 h treatment periods. The highest concentration of 4-MEI (750 μg/ml) induced MN formation more than the positive control MMC in 24 h treatment period. In addition, 4-MEI led to a decrease in MI at the highest concentration (750 μg/ml) in 24 ...
10 citations
TL;DR: Phototherapy causes an increase in the frequency of sister chromatid exchange regardless of the irradiance, which could have some genotoxic adverse effects on chromosomes; however, further investigations are warranted to enlighten as to whether these effects are permanent or clinically important.
Abstract: Aim Concerns of possible genotoxic effects of hyperbilirubinemia and phototherapy were raised from experimental and observational studies in neonates. The purpose of this study was to assess the effect of hyperbilirubinemia and phototherapy with three different methods on DNA damage by investigating sister chromatid exchange frequency. Material and Methods Patients whose gestational ages were >37 weeks and bilirubin levels above phototherapy limits were enrolled into three groups and each group was planned to receive 25 babies. Group 1 received enhanced light-emitting diode phototherapy, group 2 had light-emitting diode phototherapy, and group 3 received conventional phototherapy. Infants with hyperbilirubinemia but did not require phototherapy comprised the control group, which was subdivided into two groups regarding bilirubin levels ( 10mg/dL). Blood samples were collected before and after phototherapy for sister chromatid exchange frequency and samples were examined by a biologist who was blinded to the study groups. Results The mean pre-treatment sister chromatid exchange frequency was 1.41±0.34/cell, post-treatment 2.65±0.68/cell, and 1.61±0.61/cell for the control group (p<0.05). A statistically significant increase in sister chromatid exchange frequency after phototherapy was observed in all three intervention groups (p values: 0.01, 0.01, and 0.008, respectively). When the treatment groups were compared with each other in terms of irradiance, no significant difference was found (p=0.08). Conclusions Phototherapy causes an increase in the frequency of sister chromatid exchange regardless of the irradiance. Phototherapy could have some genotoxic adverse effects on chromosomes; however, further investigations are warranted to enlighten as to whether these effects are permanent or clinically important.
8 citations
TL;DR: To the authors' knowledge, this is the first report that correlates H2AX and SCE levels in primary sarcoma cell lines and may provide insight into potential response to DNA-damaging treatments.
Abstract: Sarcomas are rare heterogeneous malignancies of mesenchymal origin characterised by complex karyotypes but no specific abnormalities. Recurrence is common, and metastatic disease carries poor survival despite standard DNA-damaging radiotherapy or chemotherapy. DNA double-strand breaks (DSBs) are either repaired by mechanisms such as homologous recombination (HR) or result in cell death by apoptosis. Endogenous γH2AX formation and SCE formation are early and late events, respectively, and their levels are considered surrogate measures of genomic instability. Combined γH2AX and SCE analysis was used to evaluate endogenous DNA DSB levels (and their subsequent repair) in 9 primary sarcoma cell lines and compared with well-established commercial lines. All the sarcoma cell lines had elevated γH2AX and SCE levels, but there was no correlation between the DNA DSB frequency and subsequent SCE. Typically, radioresistant osteosarcoma cells had relatively low γH2AX frequency but high SCE counts suggestive of efficient DNA repair. Conversely, liposarcoma cells derived from a radiosensitive tumour had high H2AX but relatively lower SCE levels that may imply inefficient DNA DSB repair. To our knowledge, this is the first report that correlates H2AX and SCE levels in primary sarcoma cell lines and may provide insight into potential response to DNA-damaging treatments.
6 citations
TL;DR: The study suggested that RJ protected human cells from DXR-induced genotoxicity, possibly mediated through anti-apoptotic, anti-oxidative, and anti-aging properties of RJ, however, lower doses of RJ co-treatments enhanced DXR toxicity.
Abstract: Genoprotective effects of royal jelly (RJ) treatments against doxorubicin (DXR), a potent genotoxic chemotherapeutic compound in human lymphocytes were investigated using the sister chromatid excha...
5 citations
TL;DR: It is shown that non-random sister chromatid segregation during asymmetric division of Drosophila male germline stem cells is mediated by ribosomal DNA (rDNA) loci, consisting of hundreds of tandemly repeated rDNA units.
Abstract: Although non-random sister chromatid segregation has been proposed to underlie asymmetric cell divisions, the underlying biological significance or mechanisms remained elusive. Here we show that non-random sister chromatid segregation during asymmetric division of Drosophila male germline stem cells is mediated by ribosomal DNA (rDNA) loci, consisting of hundreds of tandemly repeated rDNA units. We identify a novel zinc-finger protein CG2199/Indra that binds to rDNA and control non-random sister chromatid segregation. Our data indicate that non-random sister chromatid segregation may reflect the segregation of sister chromatids with different rDNA copy numbers after unequal sister chromatid exchange to maintain rDNA copy number through generations. To our knowledge, this is the first study to provide mechanistic insights into the mechanism of non-random sister chromatid segregation.
3 citations
TL;DR: The highest concentration of pristine CNTs induced the most chromatid and chromosomal damage, and although the percentage was less than 10%, such degree of damage is considered harmful to cells.
Abstract: Objective: evaluate the genotoxic and mutagenic effect in human lymphocytes exposed to pristine and N-doped carbon nanotubes. Methods: Methods: human lymphocytes were exposed to pristine and N-doped carbon nanotubes (NTC) (0.08, 0.09, 0.1mg/mL). Sister chromatid exchange (SCE) and chromosomal alterations (CA) tests were evaluated. Results: chromatid breaks and chromosomal breaks (double strand breaks) were identified in lymphocytes exposed to 0.1 and 0.08 mg/mL of the pristine CNT. N-doped CNT, induced dicentric chromosomes and chromosomal rings. There was significant difference in the percentage of SCE of cells treated with doped NTC versus negative control and pristine NTC (p<0.0001). Conclusion: the highest concentration of pristine CNTs induced the most chromatid and chromosomal damage. Although the percentage was less than 10%, such degree of damage is considered harmful to cells. Lymphocytes treated with N-doped CNT presented lower percentages of CA and high percentage of SCE, which shows a greater repair of genetic material with these compounds.