Showing papers on "Sister chromatid exchange published in 2003"
TL;DR: The data suggest that PARP-1 controls DNA damage recognised by HR and that it is not involved in executing HR as such.
Abstract: Cells with non-functional poly(ADP-ribose) polymerase (PARP-1) show increased levels of sister chromatid exchange, suggesting a hyper recombination phenotype in these cells. To further investigate the involvement of PARP-1 in homologous recombination (HR) we investigated how PARP-1 affects nuclear HR sites (Rad51 foci) and HR repair of an endonuclease-induced DNA double-strand break (DSB). Several proteins involved in HR localise to Rad51 foci and HR-deficient cells fail to form Rad51 foci in response to DNA damage. Here, we show that PARP-1 mainly does not localise to Rad51 foci and that Rad51 foci form in PARP-1-/- cells, also in response to hydroxyurea. Furthermore, we show that homology directed repair following induction of a site-specific DSB is normal in PARP-1-inhibited cells. In contrast, inhibition or loss of PARP-1 increases spontaneous Rad51 foci formation, confirming a hyper recombination phenotype in these cells. Our data suggest that PARP-1 controls DNA damage recognised by HR and that it is not involved in executing HR as such.
297 citations
TL;DR: In this article, the effects of patulin (PAT) and citrinin (CTN) on mammalian cells were evaluated for their genotoxic effects and oxidative damage to mammalian cells, including Chinese hamster ovary cells, human peripheral blood lymphocytes, and human embryonic kidney cells (HEK293).
180 citations
TL;DR: This work shows that equal SCE is a major mechanism of DSB repair, is Rad51 dependent, and is stimulated by Rad59 and Mre11, and provides a physical analysis of mitotically occurring SCE in vivo.
101 citations
TL;DR: RecQL1 and RecQL5 are somehow involved in cell viability under the BLM function-impaired condition, and surprisingly, RECQL5+/− /BLM−/− cells showed a higher frequency of SCE than BLM−/+ cells, indicating thatRecQL5 suppresses SCE under theBLM function-impaired condition.
Abstract: Human RECQL1 and RECQL5 belong to the RecQ family that includes Bloom syndrome, Werner syndrome, and Rothmund-Thomson syndrome causative genes. Cells derived from individuals suffering from these syndromes show significant levels of genomic instability. However, neither RECQL1 nor RECQL5 has been related to a disease, and nothing is known about the functions of RecQL1 and RecQL5. We generated here RECQL1(-/-), RECQL5(-/-), RECQL1(-/-)/RECQL5(-/-), RECQL1(-/-)/BLM(-/-), and RECQL5(-/-)/BLM(-/-) cells from chicken B-lymphocyte line DT40 cells. Although BLM(-/-) DT40 cells showed a slow-growth phenotype, a higher sensitivity to methyl methanesulfonate than the wild type, and an approximately 10-fold increase in the frequency of sister chromatid exchange (SCE) compared to wild-type cells, RECQL1(-/-), RECQL5(-/-), and RECQL1(-/-)/RECQL5(-/-) cells showed no significant difference from the wild-type cells in growth, sensitivity to DNA-damaging agents, and the frequency of SCE. However, both RECQL1(-/-)/BLM(-/-) and RECQL5(-/-)/BLM(-/-) cells grew more slowly than BLM(-/-) cells because of the increase in the population of dead cells, indicating that RecQL1 and RecQL5 are somehow involved in cell viability under the BLM function-impaired condition. Surprisingly, RECQL5(-/-)/BLM(-/-) cells showed a higher frequency of SCE than BLM(-/-) cells, indicating that RecQL5 suppresses SCE under the BLM function-impaired condition.
93 citations
TL;DR: Results indicate that vanadium(IV) tetraoxide is capable of inducing cytotoxic and cytostatic effects and chromosomal damage.
81 citations
TL;DR: It is indicated that carbosulfan has a higher potential to cause genetic alterations than cypermethrin in mice and may also pose a mutagenic risk to human beings.
Abstract: The public health effects of pesticides cannot be denied. However, the undesired effects of chemical pesticides have been recognized as a serious public health concern during the past decades. The present study describes the genotoxic effects of two pesticides, namely cypermethrin and carbosulfan, in a murine test system in vivo. The test parameter used was analysis of sister chromatid exchanges (SCE) in bone marrow cells. Both cypermethrin (5, 10 and 20 mg/kg) and carbosulfan (1.25, 2.5 and 5 mg/kg) induced significant increases in the frequency of SCEs (P < 0.001). However, no significant dose-response correlation could be found for either of the pesticides. Carbosulfan induced a cell cycle delay, as evidenced by an increase in average generation time accompanied by accumulation of cells in the first division cycle, but cypermethrin did not induce any such response. The present study indicates that carbosulfan has a higher potential to cause genetic alterations than cypermethrin in mice and may also pose a mutagenic risk to human beings.
61 citations
TL;DR: Observations indicate that most likely β-carotene breakdown products are responsible for the occurrence of carcinogenic effects found in the Alpha-Tocopherol Beta- carotene-Cancer prevention study and the beta-CArotene and RETinol Efficacy (CARET) Trial.
Abstract: According to Siems and his colleagues, free radical attack on β-carotene results in the formation of high amounts of cleavage products with prooxidant activities towards subcellular organelles such as mitochondria. This finding may give an explanation for the contradictory results obtained with β-carotene in clinical efficacy and cancer prevention trials. Since primary hepatocytes proved to be very sensitive indicators for the genotoxic action of suspect mutagens/carcinogens we therefore investigated a β-carotene cleavage products mixture (CP), apo8´-carotenal (apo8´) and β-carotene utilising primary cultures of rat hepatocytes. The endpoints tested were: the mitotic index, the percentage of necrotic and apoptotic cells, micronucleated cells, chromosomal aberrations and SCE (sister chromatid exchanges). Our results indicate a genotoxic potential of both CP and apo8´ already in the concentration range of 100 nM and 1 µM, i.e. at pathophysiologically relevant levels of β-carotene and β-carotene breakdown products. A 3h treatment with CP induced statistically significant levels of micronuclei at concentrations of 0.1, 1 and 10µM, and chromosomal aberrations at concentrations of 1, 5 and 10µM. Apo8´ induced statistically significant levels of micronuclei at concentrations of 0.1, 1 and 5µM, and chromosomal aberrations at concentrations of 0.1, 1 and 10µM. Statistically significant increases of SCE induction were only observed at a concentration of 10 µM of CP and apo8’. In contrast, no significant cytotoxic effects of these substances were observed. Since β-carotene induced neither significant cytotoxic nor genotoxic effects at concentrations ranging from 0.01 up to 10 µM, these observations indicate that most likely β-carotene breakdown products are responsible for the occurrence of carcinogenic effects found in the Alpha-Tocopherol Beta-carotene-Cancer prevention (ATBC) study and the beta-CArotene and RETinol Efficacy (CARET) Trial.
57 citations
TL;DR: The obtained results suggest that low density ELF-EMF could act as an enhancer of the initiation process of BP rather than as an initiator of mutagenic effects in human lymphocytes.
57 citations
TL;DR: The results suggest a genotoxic and cytotoxic effect of MTZ and ONZ in human peripheral blood cultures in vitro and establish the value of cytogenetic assays to settle an improved risk assessment.
55 citations
TL;DR: It is proposed that gap repair mechanisms are important in DNA damage-associated recombination, whereas alternative pathways, including a template switch pathway, play a role in spontaneous SCE.
Abstract: Sister chromatid exchange (SCE) can occur by several recombination mechanisms, including those directly initiated by double-strand breaks (DSBs), such as gap repair and break-induced replication (BIR), and those initiated when DNA polymerases stall, such as template switching. To elucidate SCE recombination mechanisms, we determined whether spontaneous and DNA damage-associated SCE requires specific genes within the RAD52 and RAD3 epistasis groups in Saccharomyces cerevisiae strains containing two his3 fragments, his3-Δ5′ and his3-Δ3′::HOcs. SCE frequencies were measured after cells were exposed to UV, X-rays, 4-nitroquinoline 1-oxide (4-NQO) and methyl methanesulfonate (MMS), or when an HO endonuclease-induced DSB was introduced at his3-Δ3′::HOcs. Our data indicate that genes involved in gap repair, such as RAD55, RAD57 and RAD54, are required for DNA damage-associated SCE but not for spontaneous SCE. RAD50 and RAD59, genes required for BIR, are required for X-ray-associated SCE but not for SCE stimulated by HO-induced DSBs. In comparison with wild type, rates of spontaneous SCE are 10-fold lower in rad51 rad1 but not in either rad51 rad50 or rad51 rad59 double mutants. We propose that gap repair mechanisms are important in DNA damage-associated recombination, whereas alternative pathways, including a template switch pathway, play a role in spontaneous SCE.
54 citations
TL;DR: Genotoxic and antigenotoxic activities of carvacrol were investigated by the in vitro sister chromatid exchange (SCE) assay on human peripheral blood lymphocytes, indicating its potential for use as an antigenot toxic agent.
Abstract: Carvacrol is a predominant aromatic compound in oil of oregano. It has naturally remarkable antibacterial, antiviral, antifungal and antiparasital effects. In this study, genotoxic and antigenotoxic activities of carvacrol were investigated by the in vitro sister chromatid exchange (SCE) assay on human peripheral blood lymphocytes. The genotoxicity test was performed with carvacrol in two donors. On the other hand, inhibitory effect of carvacrol was tested in the presence of mitomycin C (MMC) in the same assay. According to data, all doses of carvacrol did not increase the formation of SCE, whereas it inhibited the rate of SCE induced by MMC. In conclusion, carvacrol exhibited a significant antigenotoxic activity in mammalian cells, indicating its potential for use as an antigenotoxic agent.
TL;DR: The present data indicate that the generation of ROS by ARC could partially contribute to the induction of chromosomal aberrations (CAs), since the frequency of ARC-induced CAs was reduced either by post-treatment with superoxide dismutase (SOD) or in anoxic conditions.
Abstract: The mutagenic and carcinogenic potency of betel-nut components is well established. This study was undertaken to determine the genotoxic potency of an aqueous extract of raw betel nut (AEBN) in relation to the endogenous glutathione (GSH) level in mouse bone marrow cells (BMC) and human peripheral blood lymphocytes (PBLs), and to find out whether arecoline (ARC), an alkaloid of betel nut, could generate reactive oxygen species (ROS) in these cells. It was observed that AEBN has genotoxic properties, which is further enhanced by depletion of endogenous GSH levels. However, the degree of enhancement varies with the type of parameter and cell system studied. The present data indicate that the generation of ROS by ARC could partially contribute to the induction of chromosomal aberrations (CAs), since the frequency of ARC-induced CAs was reduced either by post-treatment with superoxide dismutase (SOD) or in anoxic conditions. However, the induction of sister chromatid exchanges (SCEs) probably involves p53-dependent changes in cell proliferation and allowing some repair of DNA damage. The extent of damage for each parameter was higher when the mice were exposed to AEBN for 30 days than 5 days. Longer exposure showed higher level of p53 expression in mouse BMC, which could block the damaged cells from proliferation and allow the cells to repair the DNA damage.
TL;DR: The present observation on the effect of chronic low doses of I-131 and Tc-99m indicates the possibility of genotoxic implications of this type of occupational exposure, and personnel who work in nuclear medicine departments should carefully apply the radiation protection procedures.
Abstract: Objective : The aim of this study was to assess whether occupational exposure to chronic, low doses of Iodine 131 (I-131) and Technetium 99m (Tc-99m) may lead to genotoxicity. Medical personnel occupied in nuclear medicine departments are occupationally exposed to low doses of I-131 and Tc-99m. The determination of the frequency of sister chromatid exchanges (SCEs) and of cells with a high frequency of SCEs (HFC) is considered to be a sensitive indicator for detecting genotoxic potential of mutagenic and carcinogenic agents. Therefore, we examined peripheral lymphocytes from nuclear medicine physicians for the presence of both SCE and HFC. Methods : Sixteen exposed nuclear medicine physicians (non-smokers) were compared to 16 physicians (non-smokers) who had not been exposed to chemical or physical mutagens in their usual working environment at the same hospital. Results : A statistically significant difference was found between SCE frequencies and HFC percentages measured in lymphocytes from the exposed and control groups. Conclusions : The present observation on the effect of chronic low doses of I-131 and Tc-99m indicates the possibility of genotoxic implications of this type of occupational exposure. Hence, the personnel who work in nuclear medicine departments should carefully apply the radiation protection procedures and should minimize, as low as possible, radiation exposure to avoid possible genotoxic effects.
TL;DR: It is shown that low-level lead exposure in vitro is able to induce significant cytogenetic damage in human melanoma cells, indicating an increased sensitivity of B-Mel cells to lead acetate.
Abstract: In this study, chromosomal damage induced in vitro by lead acetate in human melanoma cells (B-Mel) was evaluated using the cytokinesis-blocked micronucleus assay and sister chromatid exchange (SCE) analysis. Lead acetate (10-6, 10-5 and 10-3 mM) induced micronuclei and SCE formation in a dose-dependent manner. Treated cells showed a decrease in cell viability but not concomitant cell death by apoptosis (lead acetate failed to induce internucleosomal DNA fragmentation at any of the doses tested). One important observation emerging from this study was that low-level lead exposure in vitro is able to induce significant cytogenetic damage in human melanoma cells, indicating an increased sensitivity of B-Mel cells to lead acetate.
TL;DR: Results indicate that organic extracts of A. blazei lineage AB97/11 present bio-antimutagenic type protective activity.
Abstract: Agaricus blazei Murill is a medicinal mushroom native to Brazil. The present work assessed the clastogenic and anticlastogenic potential of organic extracts (ethanol and chloroform/methanol) from the lineage AB97/11 in chinese hamster CHO-K(1) (wild type) and CHO-xrs5 (repair deficient) cells using the chromosome aberration (CA) and sister chromatid exchange (SCE) assays. In these experimental conditions were observed: (a) anticlastogenic effect at concentrations of 0.06 and 0.09% of the EtOH extract and at the 0.03 and 0.06% concentrations of the C/MetOH extract in CHO-K(1); (b) absence of protector effect on CHO-xrs5 cells; and (c) absence of protector effect in the SCE assay. These results indicate that organic extracts of A. blazei lineage AB97/11 present bio-antimutagenic type protective activity.
TL;DR: In this article, the in vivo antineoplastic effect of vanadium at the 0.5 ppm dosage in drinking water was investigated by monitoring hepatic nodulogenesis and hepatocellular phenotype followed by antioxidant status and atomic absorption spectrometric estimation of some essential biometals during the multistage of carcinogenesis induced by 2-acetylaminofluorene (2-AAF; 0.05% in basal diet).
Abstract: Vanadium is an important regulator of cellular growth, differentiation, and cell death, and thus has received increasing attention to be an effective cancer chemopreventive agent. In the present study, attempts have been made to investigate the in vivo antineoplastic effect of this micronutrient at the 0.5 ppm dosage in drinking water, by monitoring hepatic nodulogenesis and hepatocellular phenotype followed by antioxidant status and atomic absorption spectrometric estimation of some essential biometals during the multistage of carcinogenesis induced by 2-acetylaminofluorene (2-AAF; 0.05% in basal diet). Finally, sister-chromatid exchange (SCE) and DNA-protein crosslink (DPC) formation, as potential biomarkers were estimated to find out the suppressive effect of vanadium at the molecular level. The results showed that vanadium administration throughout the experiment reduced the relative liver weight, nodular incidence (48.40%), total number, and multiplicity (63.91%), and altered the size of visible persistent nodules (PNs) with concurrent restoration of hepatic glutathione (P < 0.01), glutathione-S-transferase (P < 0.001) and manganese-dependent superoxide dismutase (P < 0.001) activities as well as, hepatic zinc and copper contents (P < 0.001) when compared to the carcinogen control. Moreover, vanadium treatment significantly reduced SCE frequency (50.24%) and DPC coefficient (P < 0.001; 21.30%). Our results, thus, strongly suggest that supplementary vanadium at a dose of 0.5 ppm, when administered continuously throughout the study, than administered either in the initiation or promotion phase alone, is very much effective in suppressing neoplastic transformation during 2-AAF-induced in vivo rat hepatocarcinogenesis.
TL;DR: Short-term administration of sevoflurane anaesthesia did not induce SCE in T-lymphocytes of children and no indication for a possible genotoxic effect has been observed.
Abstract: Background Compound A, a degradation product of sevoflurane, has been demonstrated to induce sister chromatid exchanges (SCE) in Chinese hamster ovary cells in vitro as a marker for possible genotoxicity. We investigated the formation of SCE in mitogen-stimulated T-lymphocytes of 40 children undergoing sevoflurane anaesthesia for minor surgical procedures. Methods Anaesthesia was induced by inhalation of up to 8% sevoflurane and maintained at 2.5–3% in oxygen/nitrous oxide (65/35%) at a fresh gas flow of 3 litre min−1. Soda lime (humidity 12–15%) was used as a carbon dioxide absorbent. Blood was drawn directly before induction and after termination of anaesthesia. Twenty-five second division metaphases of mitogen-stimulated T-lymphocytes per blood sample were screened for SCE rates using standard techniques. Results Average duration of anaesthesia was 49.6 (sd 24.0) min. Before anaesthesia induction, 7.93 (1.23) SCE per metaphase were determined. After sevoflurane anaesthesia [1.40 (0.77) MAC h] 7.92 (1.19) SCE per metaphase were observed. Additionally, no differences were evident between male or female children. Conclusion Short-term administration of sevoflurane anaesthesia did not induce SCE in T-lymphocytes of children. No indication for a possible genotoxic effect has been observed.
TL;DR: The compound is able to induce mutagenic effects in bacterial strains TA100, TA1535, WP2uvrA and IC3327, as revealed by the increase observed in the number of induced revertants.
Abstract: The epoxy resin bisphenol F diglycidyl ether (BFDGE), was examined for its mutagenicity in prokaryotic assays (Salmonella typhimurium His− and Escherichia coli Trp− tests) and its genotoxicity in eukaryotic systems (sister chromatid exchange (SCE) and micronucleus tests in human lymphocytes), in the presence or absence of an exogenous metabolizing system (S9 from rat liver). In the prokaryotic tests, the concentrations of BFDGE ranged between 100 and 5000 μg per plate, and in the eukaryotic assays from 12.5 to 62.5 μg/ml. The compound is able to induce mutagenic effects in bacterial strains TA100, TA1535, WP2uvrA and IC3327, as revealed by the increase observed in the number of induced revertants. With respect to the genotoxicity assays, BFDGE induces an increase in the frequency of sister chromatid exchanges and micronuclei in human peripheral blood lymphocytes.
TL;DR: The results suggest that workers with susceptible metabolic and DNA-repair genotypes, may experience an increased risk of DNA damage elicited by VCM exposure.
Abstract: Vinyl chloride monomer (VCM) is a known human carcinogen, which may be metabolized by cytochrome P450 2E1 (CYP2E1), aldehyde dehydrogenase 2 (ALDH2), and glutathione S-transferase T1 (GSTT1). A DNA-repair gene, X-ray repair cross-complementing group 1 (XRCC1, exon 10), may also be implicated in the process of VCM-related carcinogenesis. Thus, VCM-exposed workers with inherited susceptible metabolic and DNA-repair genotypes may experience an increased risk of genotoxiciy. This study was designed to investigate whether metabolic and DNA-repair genotypes affected sister chromatid exchange (SCE) frequency in occupationally VCM-exposed workers from polyvinyl chloride (PVC) manufacturing plants. Study subjects comprised 61 male workers having experienced VCM exposure, and 29 male controls. Questionnaires were administered to obtain detailed histories of cigarette-smoking habits, alcohol consumption behavior, and occupation. The frequency of SCE in peripheral lymphocytes was determined using a standardized method, and genotypes of CYP2E1, ALDH2, GSTT1 and XRCC1 were identified by the polymerase chain reaction (PCR) procedure. Our results demonstrated that smoking, age and VCM exposure and XRCC1 (P=0.03), CYP2E1 (P=0.04), and ALDH2 (P=0.08) were significantly associated with an increased SCE frequency. Further analysis of gene combinations, including CYP2E1, ALDH2 and XRCC1, revealed an increased trend for these genotypes to influence SCE frequencies for the low VCM-exposure group (P<0.01), but not so for the high VCM-exposure group (P=0.29) or for controls (P=0.49). These results suggest that workers with susceptible metabolic and DNA-repair genotypes, may experience an increased risk of DNA damage elicited by VCM exposure.
TL;DR: The MMR system is involved in the generation of chromosomal damage in cells exposed to 6-thioguanine, and does not confer protection against the clastogenic effects of CCNU, at least in the cell lines investigated.
Abstract: Purpose
The mismatch repair (MMR) system plays a major role in mediating the cytotoxicity and clastogenicity of agents generating O6-methylguanine in DNA. Loss of MMR has also been associated with tumor cell resistance to the cytotoxic effects of 6-thioguanine and cisplatin and with hypersensitivity to N-(2-chloroethyl)-N′-cyclohexyl-N-nitrosourea (CCNU). The aim of the present investigation was to elucidate the role played by the MMR system in the generation of chromosomal damage in cells exposed to 6-thioguanine, cisplatin or CCNU.
TL;DR: A new cytogenetic approach for genotoxic studies is presented that enables the analysis of SCEs directly in G2 phase using drug-induced premature chromosome condensation in cultured peripheral blood lymphocytes, and shows that a higher SCE frequency was scored in G1 phase than in metaphase.
Abstract: The aim of the present study was to develop and standardize a cytogenetic approach for evaluation of the mutagenic potential of chemicals that induce cell cycle arrest in the G2 phase. Even though cytogenetic end-points such as sister chromatid exchange (SCE) have been extensively used to indirectly assess the DNA-damaging potential of various chemicals, they are based on metaphase chromosome analysis. Cells delayed in G2 phase after chemical exposure are not included in conventional SCE analysis. The yield of SCEs obtained, therefore, can be biased, since predominantly undamaged cells proceed to metaphase without delay. To overcome this shortcoming of conventional SCE analysis, the use of a new cytogenetic approach for genotoxic studies is presented that enables the analysis of SCEs directly in G2 phase using drug-induced premature chromosome condensation in cultured peripheral blood lymphocytes. By means of this method, firstly, the possibility that SCE analysis in metaphase chromosomes underestimates the mutagenic potential of various chemicals was tested. Secondly, whether the genotoxic potential of suspected carcinogens could be evaluated using SCE analysis in G2 phase, even at exposures that arrest cells in G2 phase, was examined. Thirdly, whether an important part of the background variation in SCE frequency among individuals is due to the delay of affected cells in G2 phase, rather than to a true biological variation in the cytogenetic end-point used, was tested. The results showed that a higher SCE frequency was scored in G2 phase than in metaphase. Subsequently, the mutagenic potential of chemicals that temporarily arrest cells in G2 phase could now be evaluated more accurately. In addition, it may be of interest to further examine the involvement of cell cycle kinetics in the baseline SCE variation among individuals since a lesser SCE variability was observed when the analysis was carried out in G2 phase rather than at metaphase.
TL;DR: The present findings corroborate the positive results from recent in vivo rodent studies and confirm the genotoxic potential of 2,4-dichlorophenoxyacetic acid in chick embryos using a test system that may provide some indications on the genetic risk to animal species in the wild.
TL;DR: It is proposed that an interstrand cross-link may be the major lesion leading to SCEs in BrdU-labelled cells.
Abstract: The role of 5-bromo-2'-deoxyuridine (BrdU) in the formation of sister chromatid exchanges (SCEs) in cells exposed to UV radiation was studied. Cells were unifilarily labelled (labelling of one strand of chromosomal DNA) with BrdU or biotin-16-2'-deoxyuridine (biotin-dU) and irradiated in G(1) phase of the cell cycle either with 254 nm, which is absorbed by all nucleobases including bromouracil (BrU) or with 313 nm radiation, which is predominantly absorbed by the BrU moiety. Elevated SCE frequencies were observed in cells irradiated at 254 nm (1.2 and 3.0 J m(-2)) which were pre-labelled with BrdU or biotin-dU. Following irradiation at 313 nm (38 and 96 J m(-2)) a statistically elevated SCE frequency was observed in cells pre-labelled with BrdU but not with biotin-dU. In cells pre-labelled with BrdU, UV-radiation at 254 nm was 50-80 times more effective in inducing SCEs than that at 313 nm. This result can be accounted for by the fact that in BrdU-DNA the cross-section for uracilyl radical and bromine atom formation is approximately 100-fold higher at 254 nm than that at 313 nm. Upon irradiation at 254 nm, BrdU had a strong sensitising effect on SCE induction: the SCE frequencies observed in cells pre-labelled with BrdU are approximately 6 times higher than in cells pre-labelled with biotin-dU. From this it follows that BrdU-induced damage is responsible for more than 80% of the SCEs formed in UV irradiated cells unifilarily labelled with BrdU. Based on photochemical considerations and the fact that chemical agents which form DNA interstrand cross-links are among the most potent inducers of SCEs, we propose that an interstrand cross-link may be the major lesion leading to SCEs in BrdU-labelled cells.
TL;DR: SCE induction in each cell division depends on the course of DNA duplication, suggesting that SCE occurs at the replication fork, and the sensitivity to SCE induction by the mutagen increases nearly proportionally to BrdU incorporation into DNA.
Abstract: The aims of the present study were to establish the following: (i) the course of sister chromatid exchange (SCE) induction by ethylnitrosourea (ENU) in the first, second and third divisions as a function of the exposure time; (ii) the persistence of SCE-inducing lesions and the determination of whether or not they are always involved in SCE formation; (iii) the effect of bromodeoxyuridine (BrdU) incorporation on the induction and persistence of SCE. Three-way differential staining of sister chromatids in murine bone marrow cells in vivo was used in the present study. The results indicate the following: (i) SCE induction in each cell division depends on the course of DNA duplication, suggesting that SCE occurs at the replication fork; (ii) the cell population under study could be considered synchronous and had a cell cycle duration of nearly 9 h; (iii) in the second and third cell divisions ENU preferentially induced SCE in the cycle in which the exposure occurred; (iv) lesions induced by exposure to ENU did not cause SCE at the same site in subsequent divisions; (v) ENU was also capable of producing a long-lasting induction of SCE in BrdU-unsubstituted DNA; (vi) the sensitivity to SCE induction by the mutagen increases nearly proportionally to BrdU incorporation into DNA.
TL;DR: The results of this study indicate that METH is a genotoxic agent and that ROS may play a role in METH‐induced genotoxicity.
Abstract: Methamphetamine (METH) is a widely abused psychomotor stimulant. Although numerous studies have examined METH-induced neurotoxicity, its ability to produce genotoxic effects has not been evaluated. In this article, we report on the genotoxicity of METH in vitro and in human METH abusers. METH induced his(+) revertants in Salmonella typhimurium strains TA98 and TA100, and increased the frequency of hprt mutants, micronuclei, and sister chromatid exchange (SCE) in cultured Chinese hamster ovary K1 (CHO-K1) cells. These METH-induced genotoxic effects were eliminated if METH exposure was conducted in the presence of rat liver S9, indicating that the genotoxicity was caused by METH, and not by metabolites of METH. In addition, reactive oxygen species (ROS) scavengers inhibited the METH-induced micronuclei in CHO-K1 cells. Further investigation with 76 human long-term METH abusers and 98 unexposed controls demonstrated that total METH exposure correlated with micronucleus and SCE frequencies in cultured lymphocytes. The results of this study indicate that METH is a genotoxic agent and that ROS may play a role in METH-induced genotoxicity.
TL;DR: SCE and MN analysis failed to detect any statistically significant increase in the people exposed to simazine when compared with the controls, but with respect to high frequency cells (HFC), a statistically significant difference was detected between exposed and control groups.
Abstract: In some cities of the autonomous community of Extremadura (south-west of Spain), levels of simazine from 10 to 30 ppm were detected in tap water. To analyse the possible effect of this herbicide, two biomarkers, sister chromatid exchanges (SCE) and micronuclei (MN), were used in peripheral blood lymphocytes from males exposed to simazine through drinking water. SCE and MN analysis failed to detect any statistically significant increase in the people exposed to simazine when compared with the controls. With respect to high frequency cells (HFC), a statistically significant difference was detected between exposed and control groups.
TL;DR: The results imply that SCE-inducing lesions produced by MMS and EMS are only partially repaired and that BrdU incorporation could sensitize DNA not only to the induction of lesions eliciting SCE, but also toThe induction of non-repairable lesions.
Abstract: The repairability during G1 of DNA lesions eliciting sister chromatid exchanges (SCE) induced by methylmethanesulfonate (MMS) and ethylmethanesulfonate (EMS) in BrdU-substituted and unsubstituted DNA strands was determined in murine salivary gland cells in vivo. The SCE frequency was determined after exposure to MMS or EMS during early and late G1 in the first or second cell division. The inducibility and repairability of SCE-eliciting lesions during G1 in BrdU-substituted and unsubstituted strands were estimated considering that in the first division induction occurs on the unsubstituted strand and during the second division in one unsubstituted and one BrdUsubstituted DNA strand. The results indicate that DNA lesions induced by MMS are 50% repaired in both the BrdU-substituted and unsubstituted strands and those induced by EMS are 60% repaired in the unsubstituted strand but only 20% in the BrdU-substituted strand. The increase in sensitivity of the BrdU-substituted strand to SCE induction with respect to the unsubstituted strand was 155 and 45% for MMS and EMS, respectively. These results imply that SCE-inducing lesions produced by MMS and EMS are only partially repaired and that BrdU incorporation could sensitize DNA not only to the induction of lesions eliciting SCE, but also to the induction of nonrepairable lesions.
TL;DR: Investigation of the mutagenic effects of different PUVA doses on DNA with SCE analysis found that PUVA treatment seemed to increase SCE values; however, there was not a correlation betweenPUVA doses and SCE frequencies.
Abstract: BACKGROUND: Psoralen+ultraviolet A (UVA) (PUVA) is used successfully in the treatment of several skin diseases including psoriasis. PUVA has been reported to cause skin cancers, especially when used in high doses. In vivo and in vitro effects of different mutagens and carcinogens on DNA may be detected by sister chromatid exchange (SCE). OBJECTIVE: To investigate the mutagenic effects of different PUVA doses on DNA with SCE analysis. MATERIALS AND METHODS: Forty-two psoriasis patients under PUVA treatment were included in the study as the study group. The control group consisted of 22 psoriasis patients who did not receive PUVA treatment. The study group was divided into three groups according to PUVA doses. SCE/cell values were compared in the study and control groups and in the three dose-dependent groups of the study group. RESULTS: Mean SCE/cell values of the three dose-dependent patient groups were significantly higher than the control group ( p <0.001), whereas there was not a statistically signific...
TL;DR: This study sought to determine whether workers exposed to ETU showed thyroid hormone changes compared to a nonexposed comparison group, and looked at sister chromatid exchange (SCE) and chromosomal translocations (balanced chromosomal aberrations that are not cell lethal) in the lymphocytes of exposed workers and nonexposed controls.
Journal Article•
TL;DR: The increased sister chromatid exchange frequency and low mitotic index may be reflecting a direct genotoxic effect of HBV and HCV in peripheral lymphocytes, suggesting that the same genotoxicity may also operate in the liver and contribute to hepatocarcinogenesis.
Abstract: Background/Aims: It is controversial whether hepatitis B or C viruses induce liver cancer through non-specific mechanisms (inflammation and cell renewal) or direct genotoxicity. Considering that both viruses infect peripheral lymphocytes, studying sister chromatid exchange frequency and mitotic index in peripheral lymphocytes is a reasonable experimental approach to investigate their genotoxic potential separately. In the present study we investigated sister chromatid exchange frequency and mitotic index in the peripheral lymphocytes of patients with cirrhosis and chronic carriers with positive serology for HBV or HCV infections. Methodology: The study population consisted of 3 groups; groups I involved 23 HBsAg positive chronic carriers; group II involved 30 HBsAg positive patients with cirrhosis and group III involved 9 HCV-positive patients with cirrhosis. The control group involved 30 healthy individuals. Results: Sister chromatid exchange frequency was significantly higher in all the study groups than the control group (p<0.05). The mitotic index was significantly lower in all the study groups than the control group (p<0.05). Conclusions: The increased sister chromatid exchange frequency and low mitotic index may be reflecting a direct genotoxic effect of HBV and HCV in peripheral lymphocytes. We suggest that the same genotoxicity may also operate in the liver and contribute to hepatocarcinogenesis.