Showing papers on "Sister chromatid exchange published in 2009"
TL;DR: The present results indicate that the SCE-frequency in healthy human subjects is influenced by individual smoking habits as well and strongly suggest occupational exposure as a causative factor.
Abstract: The analysis of sister chromatid exchange (SCE) might be a useful technique for the study of genetic damage in humans exposed to environmental mutagens and carcinogens. To obtain reference values for such studies we have analysed SCE-frequencies in peripheral lymphocytes of 43 healthy, occupationally non-exposed human subjects. Among these subjects cigarette smokers were found to have significantly higher SCE-frequencies (16.2±SD 3.6) than non-smokers (13.1±2.9). When smokers were subdivided into moderate (<10 cig. per day) and heavy (≥10cig. per day) smokers, a clear dose-effect of smoking on the SCE frequency was noted. This observation was supported by a retrospective inquiry into the smoking habits of 18 previously analysed psoriasis patients, among whom SCE-frequencies of 16.8±2.4 and 13.7±3.1 were recorded for smokers and non-smokers, respectively. In a group of 19 laboratory workers there was no significant difference between smokers (18.6±3.3) and non-smokers (19.5±5.0). The significantly increased SCE-frequencies recorded in this group support earlier observations and strongly suggest occupational exposure as a causative factor. The present results indicate that the SCE-frequency in healthy human subjects is influenced by individual smoking habits as well.
188 citations
TL;DR: The effects of individual smoking habits should be taken into account in evaluations of the effects of exogenous agents on SCE frequencies, on the basis of the present data, which confirm previous results.
Abstract: The present survey comprises analysis of sister chromatid exchange (SCE) frequencies in the peripheral blood lymphocytes of 100 subjects: 83 healthy men and women, both cigarette smokers and nonsmokers and 17 children. Both for men (30 smoking, 22 nonsmoking) and for women (13 smoking, 18 nonsmoking) the frequency of SCEs is significantly higher among smokers (group mean 9.6±S.E. 0.2) than among nonsmokers (group mean 8.1±S.E. 0.2). No difference is detected in the frequencies of metaphase chromosome aberrations analysed in the cultured lymphocytes of the same subjects. Young children (17 subjects, mean age 1.5 years) show a significantly lower frequency of SCEs (mean 5.1±0.6) than adults.
While the induction of SCEs is known to provide a sensitive indicator of mutagen/carcinogen exposure in experimental assays, it may also give important information of in vivo exposure to genotoxic agents. However, on the basis of the present data, which confirm previous results, the effects of individual smoking habits should carefully be taken into account in evaluations of the effects of exogenous agents on SCE frequencies.
109 citations
TL;DR: The genetic dissection of FANCM indicates that it functions with the Blm helicase to suppress spontaneous SCE events and the role of helicase domain associated activities is reappraised with respect to the activation of the FA pathway, crosslink repair and in the resolution of recombination intermediates.
Abstract: FANCM, the most highly conserved component of the Fanconi Anaemia (FA) pathway can resolve recombination intermediates and remodel synthetic replication forks. However, it is not known if these activities are relevant to how this conserved protein activates the FA pathway and promotes DNA crosslink repair. Here we use chicken DT40 cells to systematically dissect the function of the helicase and nuclease domains of FANCM. Our studies reveal that these domains contribute distinct roles in the tolerance of crosslinker, UV light and camptothecininduced DNA damage. Although the complete helicase domain is critical for crosslink repair, a predicted inactivating mutation of the Walker B box domain has no impact on FA pathway associated functions. However, this mutation does result in elevated sister chromatid exchanges (SCE). Furthermore, our genetic dissection indicates that FANCM functions with the Blm helicase to suppress spontaneous SCE events. Overall our results lead us to reappraise the role of helicase domain associated activities of FANCM with respect to the activation of the FA pathway, crosslink repair and in the resolution of recombination intermediates.
84 citations
TL;DR: It is found that both Tipin and And1 promote stable binding of Polα to chromatin and that this is required for DNA replication under unchallenged conditions.
Abstract: The Tipin/Tim1 complex plays an important role in the S-phase checkpoint and replication fork stability. However, the biochemical function of this complex is poorly understood. Using Xenopus laevis egg extract we show that Tipin is required for DNA replication in the presence of limiting amount of replication origins. Under these conditions the DNA replication defect correlates with decreased levels of DNA Polα on chromatin. We identified And1, a Polα chromatin-loading factor, as new Tipin-binding partner. We found that both Tipin and And1 promote stable binding of Polα to chromatin and that this is required for DNA replication under unchallenged conditions. Strikingly, extracts lacking Tipin and And1 also show reduced sister chromatids cohesion. These data indicate that Tipin/Tim1/And1 form a complex that links stabilization of replication fork and establishment of sister chromatid cohesion.
70 citations
TL;DR: The results suggest that loss of the PALB2-MRG15 interaction relieved the cells with the suppression of sister chromatid exchange and therefore led to a hyper-recombination phenotype in the gene conversion assay.
69 citations
TL;DR: Evidence is presented that Elg1, Ctf4, and Ctf18 may coordinate the relative movement of the replication fork with respect to the cohesin ring, and that CTF18 and Elg 1 affect cohesion via a joint pathway.
Abstract: Mutations in the ELG1 gene of yeast lead to genomic instability, manifested in high levels of genetic recombination, chromosome loss, and gross chromosomal rearrangements. Elg1 shows similarity to the large subunit of the Replication Factor C clamp loader, and forms a RFC-like (RLC) complex in conjunction with the 4 small RFC subunits. Two additional RLCs exist in yeast: in one of them the large subunit is Ctf18, and in the other, Rad24. Ctf18 has been characterized as the RLC that functions in sister chromatid cohesion. Here we present evidence that the Elg1 RLC (but not Rad24) also plays an important role in this process. A genetic screen identified the cohesin subunit Mcd1/Scc1 and its loader Scc2 as suppressors of the synthetic lethality between elg1 and ctf4. We describe genetic interactions between ELG1 and genes encoding cohesin subunits and their accessory proteins. We also show that defects in Elg1 lead to higher precocious sister chromatid separation, and that Ctf18 and Elg1 affect cohesion via a joint pathway. Finally, we localize both Ctf18 and Elg1 to chromatin and show that Elg1 plays a role in the recruitment of Ctf18. Our results suggest that Elg1, Ctf4, and Ctf18 may coordinate the relative movement of the replication fork with respect to the cohesin ring.
67 citations
TL;DR: The results point at an S phase-specific role for ESCO2 in the maintenance of genome stability, in contrast to a previous study on cells from patients with Cornelia de Lange syndrome, where RBS cells failed to exhibit excessive chromosome aberrations after irradiation in G2 phase of the cell cycle.
Abstract: Cohesion between sister chromatids is essential for faithful chromosome segregation. In budding yeast, the acetyltransferase Eco1/Ctf7 establishes cohesion during DNA replication in S phase and in response to DNA double strand breaks in G2/M phase. In humans two Eco1 orthologs exist: ESCO1 and ESCO2. Both proteins are required for proper sister chromatid cohesion, but their exact function is unclear at present. Since ESCO2 has been identified as the gene defective in the rare autosomal recessive cohesinopathy Roberts syndrome (RBS), cells from RBS patients can be used to elucidate the role of ESCO2. We investigated for the first time RBS cells in comparison to isogenic controls that stably express V5- or GFP-tagged ESCO2. We show that the sister chromatid cohesion defect in the transfected cell lines is rescued and suggest that ESCO2 is regulated by proteasomal degradation in a cell cycle-dependent manner. In comparison to the corrected cells RBS cells were hypersensitive to the DNA-damaging agents mitomycin C, camptothecin and etoposide, while no particular sensitivity to UV, ionizing radiation, hydroxyurea or aphidicolin was found. The cohesion defect of RBS cells and their hypersensitivity to DNA-damaging agents were not corrected by a patient-derived ESCO2 acetyltransferase mutant (W539G), indicating that the acetyltransferase activity of ESCO2 is essential for its function. In contrast to a previous study on cells from patients with Cornelia de Lange syndrome, another cohesinopathy, RBS cells failed to exhibit excessive chromosome aberrations after irradiation in G2 phase of the cell cycle. Our results point at an S phase-specific role for ESCO2 in the maintenance of genome stability.
67 citations
TL;DR: The results of used assays showed that benzoic acid significantly increased the chromosomal aberration, sister chromatid exchange and micronucleus frequency without changing the pH of the medium in a dose-dependent manner.
Abstract: The chromosomal aberration (CA), sister chromatid exchange (SCE) and micronucleus test (MN) were employed to investigate the in vitro effect of antimicrobial food additive benzoic acid on human chromosomes. Lymphocytes were incubated with various concentrations (50, 100, 200 and 500 μg/mL) of benzoic acid. The results of used assays showed that benzoic acid significantly increased the chromosomal aberration, sister chromatid exchange and micronucleus frequency (200 and 500 μg/mL) without changing the pH of the medium in a dose-dependent manner. Also this additive significantly decreased the mitotic index (MI) at the highest concentration for 24 h and 100, 200 and 500 μg/mL for 48 h. This decrease was dose-dependent as well. However, it did not effect the replication (RI) and nuclear division (NDI) indices.
62 citations
TL;DR: It is indicated that cadmium, lead and zinc can induce micronucleated cells, SCEs and sperm abnormalities in Algerian mice and that the clastogenic potential is dependent on the time of exposure and the interaction between the three elements, confirming the environmental damage that may result from the simultaneous action of several metals.
Abstract: As a consequence of human activities, large amounts of cadmium, lead and zinc are released in the environment, often simultaneously. The aim of this study was to investigate under experimental conditions the DNA damage induced in Algerian mice (Mus spretus) exposed to cadmium (Cd), lead (Pb) and zinc (Zn) separately, or in selected combinations. Three cytogenetic end points were considered: the frequencies of micronucleated cells (MN) and sister chromatid exchange (SCE) in the bone marrow and the frequency of sperm abnormalities. Mice were treated by intraperitoneal (i.p.) injections with 5 or 10 doses of aqueous solutions of cadmium acetate, lead acetate and zinc acetate in concentrations corresponding to 1/10 of the LD50, respectively, 21.5, 0.46 and 1.5 mg/kg bw. The control groups were injected in the same way with distilled water. With only one exception (Cd + Zn group treated with 5 doses), the results show a significant increase of MN in all groups for both treatments (5 and 10 doses). Similarly, the results concerning the SCE revealed a statistically significant increase in all treated animals, with the exception of the Zn group treated with 5 doses. The number of sperm abnormalities was significantly higher in animals treated with 5 doses, except in the group Pb + Zn. In animals treated with 10 doses the number of sperm abnormalities was always statistically higher compared with controls. This study indicates that cadmium, lead and zinc can induce MN, SCEs and sperm abnormalities in Algerian mice and that the clastogenic potential is dependent on the time of exposure and the interaction between the three elements, confirming the environmental damage that may result from the simultaneous action of several metals. Most relevant is the toxic potential for Zn, related with the dose, which may compromise its protective effect against other metal contaminations, such as cadmium.
61 citations
TL;DR: This study suggests that, although subtelomeric DNA hypomethylation is often coincident with the ALT process in human tumor cells, it is not required for T-SCE.
Abstract: Most human tumor cells acquire immortality by activating the expression of telomerase, a ribonucleoprotein that maintains stable telomere lengths at chromosome ends throughout cell divisions. Other tumors use an alternative mechanism of telomere lengthening (ALT), characterized by high frequencies of telomeric sister chromatid exchanges (T-SCEs). Mechanisms of ALT activation are still poorly understood, but recent studies suggest that DNA hypomethylation of chromosome ends might contribute to the process by facilitating T-SCEs. Here, we show that ALT/T-SCE(high) tumor cells display low DNA-methylation levels at the D4Z4 and DNF92 subtelomeric sequences. Surprisingly, however, the same sequences retained high methylation levels in ALT/T-SCE(high) SV40-immortalized fibroblasts. Moreover, T-SCE rates were efficiently reduced by ectopic expression of active telomerase in ALT tumor cells, even though subtelomeric sequences remained hypomethylated. We also show that hypomethylation of subtelomeric sequences in ALT tumor cells is correlated with genome-wide hypomethylation of Alu repeats and pericentromeric Sat2 DNA sequences. Overall, this study suggests that, although subtelomeric DNA hypomethylation is often coincident with the ALT process in human tumor cells, it is not required for T-SCE.
53 citations
TL;DR: The potential X-ray- and heavy-ion-induced bystander effects investigated herein clearly do not exceed the experimental error and thus are either lacking or are less pronounced than the effects reported in the literature for similar end points after α-particle andX-ray exposure.
Abstract: Fournier, C., Barberet, P., Pouthier, T., Ritter, S., Fischer, B., Voss, K. O., Funayama, T., Hamada, N., Kobayashi, Y. and Taucher-Scholz, G. No Evidence for DNA and Early Cytogenetic Damage in Bystander Cells after Heavy-Ion Microirradiation at Two Facilities. Radiat. Res. 171, 530–540 (2009). The occurrence of bystander effects has challenged the evaluation of risk for heavy ions, mainly in the context of space exploration and the increasing application of carbon ions in radiotherapy. In the present study, we addressed whether heavy-ion-induced DNA and cytogenetic damage is detectable in bystander cells. The formation of γ-H2AX foci, sister chromatid exchanges and micronuclei were used as markers of damage to DNA. Normal human fibroblasts were exposed to low fluences of carbon and uranium ions, and alternatively single cells were targeted with heavy ions using the GSI microbeam. We did not observe a significant increase in the bystander formation of γ-H2AX foci, sister chromatid exchanges or m...
TL;DR: The genotoxic effects of thymol were investigated in human peripheral lymphocytes treated with 25, 50, 75, and 100 microg/ml concentrations of Thymol for 24 and 48h treatment periods by using sister chromatid exchange (SCE), chromosome aberration (CA), and micronucleus (MN) tests.
TL;DR: The present study is the first to report the genotoxic and cytotoxic effects of commercial formulation of α‐cypermethrin in peripheral blood lymphocytes.
Abstract: alpha-Cypermethrin, a highly active pyrethroid insecticide, is effective against a wide range of insects encountered in agriculture and animal husbandry The potential genotoxicity of a commercial formulation of alpha-cypermethrin (Fastac 100 EC, containing 10% alpha-cypermethrin as the active ingredient) on human peripheral lymphocytes was examined in vitro by sister chromatid exchange (SCE), chromosomal aberrations (CAs), and micronucleus (MN) tests The human lymphocytes were treated with 5, 10, 15, and 20 microg/ml of alpha-cypermethrin for 24- and 48-hr alpha-Cypermethrin induced SCEs and CAs significantly at all concentrations and treatment times and MN formation was significantly induced at 5 and 10 microg/ml of alpha-cypermethrin when compared with both the control and solvent control Binuclear cells could not be detected sufficiently in the highest two concentration of alpha-cypermethrin (15 and 20 microg/ml) for both the 24- and 48-hr treatment times alpha-Cypermethrin decreased the proliferation index (PI) at three high concentrations (10, 15, and 20 microg/ml) for both treatment periods as compared with the control groups In addition, alpha-cypermethrin reduced both the mitotic index (MI) and nuclear division index (NDI) significantly at all concentrations for two treatment periods The PI and MI were reduced by alpha-cypermethrin in a concentration-dependent manner during both treatment times In general, alpha-cypermethrin showed higher cytotoxic and cytostatic effects than positive control (MMC) at the two highest concentrations for the 24- and 48-hr treatment periods The present study is the first to report the genotoxic and cytotoxic effects of commercial formulation of alpha-cypermethrin in peripheral blood lymphocytes
TL;DR: It is shown that hamster cells deficient in the Rad 51 paralog XRCC2, a component of the Rad51B/Rad51C/ Rad51D/XR CC2 complex, reveal a bias in favor of long-tract gene conversion (LTGC) during SCR.
Abstract: Sister chromatid recombination (SCR) is a potentially error-free pathway for the repair of DNA lesions associated with replication and is thought to be important for suppressing genomic instability. The mechanisms regulating the initiation and termination of SCR in mammalian cells are poorly understood. Previous work has implicated all the Rad51 paralogs in the initiation of gene conversion and the Rad51C/XRCC3 complex in its termination. Here, we show that hamster cells deficient in the Rad51 paralog XRCC2, a component of the Rad51B/Rad51C/Rad51D/XRCC2 complex, reveal a bias in favor of long-tract gene conversion (LTGC) during SCR. This defect is corrected by expression of wild-type XRCC2 and also by XRCC2 mutants defective in ATP binding and hydrolysis. In contrast, XRCC3-mediated homologous recombination and suppression of LTGC are dependent on ATP binding and hydrolysis. These results reveal an unexpectedly general role for Rad51 paralogs in the control of the termination of gene conversion between sister chromatids.
TL;DR: The results suggest that already a slight reduction of the average transcript level in heterozygous cohesin mutants may cause perturbation of cohesion, at least in some leaf cells at distinct loci.
Abstract: In contrast to yeast, plant interphase nuclei often display incomplete alignment (cohesion) along sister chromatid arms. Sister chromatid cohesion mediated by the multi-subunit cohesin complex is essential for correct chromosome segregation during nuclear divisions and for DNA recombination repair. The cohesin complex consists of the conserved proteins SMC1, SMC3, SCC3, and an α-kleisin subunit. Viable homozygous mutants could be selected for the Arabidopsis thaliana α-kleisins SYN1, SYN2, and SYN4, which can partially compensate each other. For the kleisin SYN3 and for the single-copy genes SMC1, SMC3, and SCC3, only heterozygous mutants were obtained that displayed between 77% and 97% of the wild-type transcript level. Compared to wild-type nuclei, sister chromatid alignment was significantly decreased along arms in 4C nuclei of the homozygous syn1 and syn4 and even of the heterozygous smc1, smc3, scc3, and syn3 mutants. Knocking out SYN1 and SYN4 additionally impaired sister centromere cohesion. Homozygous mutants of SWITCH1 (required for meiotic sister chromatid alignment) displayed sterility and decreased sister arm alignment. For the cohesin loading complex subunit SCC2, only heterozygous mutants affecting sister centromere alignment were obtained. Defects of the α-kleisin SYN4, which impair sister chromatid alignment in 4C differentiated nuclei, do apparently not disturb alignment during prometaphase nor cause aneuploidy in meristematic cells. The syn2, 3, 4 scc3 and swi1 mutants display a high frequency of anaphases with bridges (~10% to >20% compared to 2.6% in wild type). Our results suggest that (a) already a slight reduction of the average transcript level in heterozygous cohesin mutants may cause perturbation of cohesion, at least in some leaf cells at distinct loci; (b) the decreased sister chromatid alignment in cohesin mutants can obviously not fully be compensated by other cohesion mechanisms such as DNA concatenation; (c) some cohesin genes, in addition to cohesion, might have further essential functions (e.g., for genome stability, apparently by facilitating correct recombination repair of double-strand breaks).
TL;DR: The particular mixture of Acm+α‐cyp synergistically induced the genotoxicity/cytotoxicity in human peripheral blood lymphocytes and inhibited nuclear division more than positive control, mitomycin C (MMC) and showed a higher cytostatic effect than MMC.
Abstract: The genotoxic effects of a particular mixture of acetamiprid (Acm, neonicotinoid insecticide) and alpha-cypermethrin (alpha-cyp, pyrethroid insecticide) on human peripheral lymphocytes were examined in vitro by chromosomal aberrations (CAs), sister chromatid exchange (SCE), and micronucleus (MN) tests. The human peripheral lymphocytes were treated with 12.5 + 2.5, 15 + 5, 17.5 + 7.5, and 20 + 10 microg/mL of Acm+alpha-cyp, respectively, for 24 and 48 h. The mixture of Acm+alpha-cyp induced the CAs and SCEs at all concentrations and treatment times when compared with both the control and solvent control and these increases were concentration-dependent in both treatment times. MN formation was significantly induced at 12.5 + 2.5, 15 + 5, 17.5 + 7.5, microg/mL of Acm+alpha-cyp when compared with both controls although these increases were not concentration-dependent. Binuclear cells could not be detected sufficiently in the highest concentration of the mixture (20 + 10 microg/mL) for both the 24- and 48-h treatment times. Mitotic index (MI), proliferation index (PI) and nuclear division index (NDI) significantly decreased because of the cytotoxic and cytostatic effects of the mixture, at all concentrations for two treatment periods. Significant decreases in MI and PI were concentration dependent at both treatment times. The decrease in NDI was also concentration-dependent at 48-h treatment period. In general, Acm+alpha-cyp inhibited nuclear division more than positive control, mitomycin C (MMC) and showed a higher cytostatic effect than MMC. Furthermore, in this article, the results of combined effects of Acm+alpha-cyp were compared with the results of single effects of Acm or alpha-cyp (Kocaman and Topaktas,2007,2009, respectively). In conclusion, the particular mixture of Acm+alpha-cyp synergistically induced the genotoxicity/cytotoxicity in human peripheral blood lymphocytes.
TL;DR: It is demonstrated that Tim reduction leads to genomic instability during unperturbed DNA replication, culminating in increased chromatid breaks and translocations (triradials, quadriradials and fusions), which indicates a pivotal role for Tim in maintaining genome stability throughout normal DNA replication.
TL;DR: This work evaluated the antigenotoxic/antimutagenic activity of the crude ethanolic extracts of Codium tomentosum Stackhouse (Chlorophyceae) (CTE), collected from The Coast of South East Marmara Sea, in human lymphocytes culture in vitro against genot toxic/mutagenic agents MMC, EMS and H(2)O(2).
TL;DR: It could be suggested that dicamba injures DNA by delivering reactive oxygen species rather than by another type of mechanism/s because its formulation contains other xenobiotic/s agents able to induce cellular and DNA damage by a different mechanisms/s.
TL;DR: It is suggested that type-1 diabetes mellitus is a condition with genomic instability characterized by an increased level of SCE, and Hyperglycemia-induced oxidative stress may be the underlying factor of the increased SCE frequency.
Abstract: Oxidative stress-induced DNA damage seems to play a role in the pathogenesis of type-1 diabetes mellitus and its complications. Several in vitro assays have been used to measure the DNA damage produced by oxidative stress. In the present study, we aimed to investigate the frequency of sister chromatid exchange (SCE), chromosomal aberrations (CA) and micronuclei (MN) in type-1 diabetes mellitus patients compared with healthy controls. SCE, CA and MN tests were carried out with the blood-cell cultures from 35 type-1 diabetic patients and 15 healthy, age- and sex-matched control subjects. The mean age of the type-1 diabetic patients was 31.89 ± 10.01 years, with a mean duration of the diabetes of 7.8 ± 6.02 years. The mean level of HbA1c of the type-1 diabetic patients was 8.37 ± 1.36%. Only three (8.5%) patients with type-1 diabetes mellitus had an HbA1c level below 7%. Patients with type-1 diabetes mellitus showed a higher frequency of SCE compared with controls (5.44 ± 1.47 and 2.54 ± 0.82, respectively, p < 0.001), but there was no significant correlation between the duration of diabetes, HbA1c and SCE. No significant difference was found in CA or MN frequency in type-1 diabetic patients compared with controls. In conclusion, these results suggest that type-1 diabetes mellitus is a condition with genomic instability characterized by an increased level of SCE. Hyperglycemia-induced oxidative stress may be the underlying factor of the increased SCE frequency.
TL;DR: A significant decrease in SCEs and CAs was observed, suggesting a protective role of apigenin against the genotoxicity of mitomycin C on mice bone marrow cells.
TL;DR: The borax concentration of 0.6 mg/ml had the most effectiveness to the lymphocyte proliferation and had the highest cytotoxicity index (CI) and significantly induced sister chromatid exchange in human chromosomes.
Abstract: Borax is used as a food additive. It becomes toxic when accumulated in the body. It causes vomiting, fatigue and renal failure. The heparinized blood samples from 40 healthy men were studied for the impact of borax toxicity on immune cell proliferation (lymphocyte proliferation) and sister chromatid exchange in human chromosomes. The MTT assay and Sister Chromatid Exchange (SCE) technic were used in this experiment with the borax concentrations of 0.1, 0.15, 0.2, 0.3 and 0.6 mg/ml. It showed that the immune cell proliferation (lymphocyte proliferation) was decreased when the concentrations of borax increased. The borax concentration of 0.6 mg/ml had the most effectiveness to the lymphocyte proliferation and had the highest cytotoxicity index (CI). The borax concentrations of 0.15, 0.2, 0.3 and 0.6 mg/ml significantly induced sister chromatid exchange in human chromosomes (P < 0.05). Borax had effects on immune cell proliferation (lymphocyte proliferation) and induced sister chromatid exchange in human chromosomes. Toxicity of borax may lead to cellular toxicity and genetic defect in human.
TL;DR: Investigation of copper extracts obtained from metallic copper in Chinese hamster ovary cell line using neutral red, sister chromatid exchange, SCE, chromosomal aberrations and cell-cycle kinetics tests shows that cells close to copper-containing materials releasing copper ions are susceptible to cytotoxic and genotoxic effects.
Abstract: The aim of this study was to investigate the cytotoxic and genotoxic effect of copper extracts obtained from metallic copper in Chinese hamster ovary (CHO-K1) cell line using neutral red (NR), sister chromatid exchange (SCE), chromosomal aberrations (CA) and cell-cycle kinetics tests. Cells were cultured in Ham-F10 with different copper-containing extracts obtained after the immersion of copper disks for 1, 2, 3, 9, 12, 24, 48 and 72 h in culture medium. Results from cytotoxicity assay showed an inverted U-shape response evidenced in changes in lysosomal activity and mitotic index. The analysis of CA revealed an increase of abnormal metaphases for copper concentration (cCu) in the 5.67-7.42 mg/L dose-range (p<0.001). In addition, SCE frequencies were higher for treated cells when compared with controls in the 1.56-7.42 mg/L concentration range (p<0.001). The absence of metaphases indicated cytotoxicity for cCu≥10.85 mg/L. Results show that cells close to copper-containing materials releasing copper ions are susceptible to cytotoxic and genotoxic effects.
TL;DR: The small, but statistically significant genotoxic burden observed in oncologic nurses of an inpatient ward emphasises the need for a continuing effort to eliminate residual occupational risks.
Abstract: Aims and objectives. To assess a possible trend in the genotoxic risk of oncologic nurses during the working year, cytogenetic biomonitoring was performed.
Background. Exposure to cytostatic agents is a major occupational concern in oncologic personnel. In contrast to the controlled environment in oncology pharmacies, nurses may be subject to unexpected events of exposure due to the intensive contact with patients.
Design and methods. The entire nursing staff of an oncology inpatient ward (n = 15) participated in a biomonitoring study over a period of nine months using the sister chromatid exchange test and the comet assay to detect DNA strand breaks. Blood samples were taken after a three-week summer break (base level), one, three, six and nine months thereafter. Airborne contaminations of cytotoxics were addressed by chromatographic methods.
Results. With regard to the single monitoring points, the comet assay revealed no significant alteration of the genotoxic burden within nine months. By contrast, the sister chromatid exchange levels were significantly increased after six and nine months when compared with base levels. A trend analysis covering the whole observation period revealed an increase in genotoxicity as shown by the sister chromatid exchange test and the alkaline but not the neutral comet assay. This increase, however, was small and reversible as shown by the trend analysis of sister chromatid exchange rates during the years of service. Air samples were negative for cytotoxic contaminants.
Conclusions and relevance to clinical practice. The small, but statistically significant genotoxic burden observed in oncologic nurses of an inpatient ward emphasises the need for a continuing effort to eliminate residual occupational risks. In comparison with historical controls, the current situation is characterised by beneficial safety improvements over the last years. Nevertheless, periodic training and awareness of the problems should be an integral part of advanced education.
TL;DR: Observations demonstrate that the association of BLM and Topoisomerase IIIα with Fanconi proteins is a functional one, delineating a BLM-Topoisomerases IIIα-Fanconi pathway that is critical for suppression of chromosome radial formation.
Abstract: The Bloom protein (BLM) and Topoisomerase IIIα are found in association with proteins of the Fanconi anemia (FA) pathway, a disorder manifesting increased cellular sensitivity to DNA crosslinking agents. In order to determine if the association reflects a functional interaction for the maintenance of genome stability, we have analyzed the effects of siRNA-mediated depletion of the proteins in human cells. Depletion of Topoisomerase IIIα or BLM leads to increased radial formation, as is seen in FA. BLM and Topoisomerase IIIα are epistatic to the FA pathway for suppression of radial formation in response to DNA interstrand crosslinks since depletion of either of them in FA cells does not increase radial formation. Depletion of Topoisomerase IIIα or BLM also causes an increase in sister chromatid exchanges, as is seen in Bloom syndrome cells. Human Fanconi anemia cells, however, do not demonstrate increased sister chromatid exchanges, separating this response from radial formation. Primary cell lines from mice defective in both Blm and Fancd2 have the same interstrand crosslink-induced genome instability as cells from mice deficient in the Fancd2 protein alone. These observations demonstrate that the association of BLM and Topoisomerase IIIα with Fanconi proteins is a functional one, delineating a BLM-Topoisomerase IIIα-Fanconi pathway that is critical for suppression of chromosome radial formation.
TL;DR: This sensitive method to detect chromosomal damage showed no elevated number of SCEs in Alzheimer's disease.
Abstract: Chromosomal abnormalities have been reported earlier in Alzheimer-type dementia. Sister chromatid exchange (SCE) was studied in four patients with Alzheimer's disease and five control subjects. The sensitive method to detect chromosomal damage showed no elevated number of SCEs in Alzheimer's disease.
Journal Article•
TL;DR: Low mitotic index, low replicative index and high frequency of anaphase anomalies in the exposed groups as compared to that of control group and all the parameters obtained from the experimental group were statistically significant when compared to the control group.
Abstract: Ciprofloxacin is a bactericidal drug which is being used widely throughout the world for the treatment of various bacterial infection. Cytotoxicity and genotoxicity of Ciprofloxacin on human lymphocytes in vitro had been assessed taking various parameters like mitotic index (MI), chromosome aberration (CA), anaphase anomalies, replicative index (RI) and sister chromatid exchange (SCE) as end points. Our results indicate low mitotic index, low replicative index and high frequency of anaphase anomalies on one hand and on other hand, high frequency of chromosome aberration and sister chromatid exchanges (SCEs) in the exposed groups as compared to that of control group. These are the indications of both cytotoxicity and genotoxicity of Ciprofloxacin on human lymphocyte culture in vitro. All the parameters obtained from the experimental group were statistically significant when compared to that of control.
Journal Article•
TL;DR: Karyological studies and sister chromatid exchange analysis were carried out in Toda buffaloes stationed at the Sheep Breeding Research Station, Sandynallah, Ooty, Tamil Nadu, and Mitosis was induced by pokeweed mitogen in short term leucocyte cultures and bromodeoxyuridine was incorporated in the cultures to elucidate the sister Chromatid exchanges.
Abstract: Karyological studies and sister chromatid exchange analysis were carried out in Toda buffaloes stationed at the Sheep Breeding Research Station, Sandynallah, Ooty, Tamil Nadu. Mitosis was induced by pokeweed mitogen in short term leucocyte cultures and bromodeoxyuridine was incorporated in the cultures to elucidate the sister chromatid exchanges. The modal chromosome number was found to be 50 (2n) as in other river type buffaloes, and the relative length of chromosomes ranged between 7.12 + 0.01 and 2.51 + 0.34. The mean sister chromatid exchange frequency was 7.8 + 0.23, and the data on SCE frequency was found to follow the Poisson distribution.
TL;DR: The slight but no significant increase of chromatide breaks frequency was observed after the exposure of lymphocytes to 80 μg/ml of bendiocarb, and mitotic index decrease was shown at the highest concentration added to the cell cultures.
Abstract: Bendiocarb is a carbamate broad-spectrum insecticide used to control disease vectors such as mosquitoes and flies, as well as household and agricultural pests. Nowadays, only few papers reporting cytogenetic or possible genotoxic effect of this insecticide on mammalian cells are available. In the present study 24-hour exposure to bendiocarbamate at concentrations ranging from 20 to 160 µg/ml was used for investigation of unstable chromosomal aberrations (CA), sister chromatid exchanges (SCE) and stable chromosomal aberration induction in cultured bovine peripheral lymphocytes. The slight but no significant increase of chromatide breaks frequency was observed after the exposure of lymphocytes to 80 µg/ml of bendiocarb. At the highest concentration added to the cell cultures (160 µg/ml) mitotic index decrease was shown in both donors (p < 0.05; p < 0.01). Both statistically significant elevation of SCEs (p < 0.05) and a reduction of proliferative indices (PI) (p < 0.01) were shown at a dose of 80 µg/ml. By means of two fluorescent-labelled whole chromosome-painting probes, stable aberrations such as bovine chromosome 1 and 5 translocation as well as numerical aberrations (polyploidies, heteroploidies) were visualised under fluorescent microscope in some examined metaphases.