Frequency Of Sister Chromatid Exchanges Research Articles

Assessment of the genotoxic effects of antihypertensive drug active ingredient indapamide in human lymphocytes

Hypertension is the most common cardiovascular disease and is also known as high blood pressure. The large majority of hypertensive patients need long-term administration of antihypertensive agents. Indapamide is an orally administered diuretic antihypertensive drug. The present work aimed to assess the possible genotoxic effects of indapamide using four different assays: chromosomal aberration (CA), sister chromatid exchange (SCE), micronucleus (MN), and comet. Lymphocytes from three different donors were exposed to 18.75, 37.50, 75.00, and 100.00 μg/ml indapamide. Additionally, a negative, a positive (mitomycin C = MMC, 0.20 μg/ml), and a solvent control (5.4 μl/ml methanol) were also applied. As a result, it was seen that indapamide did not cause a significant change in CAs and MN frequencies compared to the control. It caused significant damage only at the highest concentration in the comet assay. Similarly, while it did not affect the number of SCEs in the 24-h treatment, it increased the SCE frequency at the two highest concentrations in the 48-h. Mitotic index (MI) decreased at almost all concentrations. Considering all these results, this study revealed that indapamide did not have a significant genotoxic effect in these conditions. To the best of our knowledge, this is the first investigation about the genotoxic effect of indapamide in human lymphocytes in vitro.

Cellular consequences of small supernumerary marker chromosome derived from chromosome 12: mosaicism in daughter and father.

Constitutional genomic imbalances are known to cause malformations, disabilities, neurodevelopmental delay, and dysmorphia and can lead to dysfunctions in the cell cycle. In extremely rare genetic conditions such as small supernumerary marker chromosomes (sSMC), it is important to understand the cellular consequences of this extra marker, as well the factors that contribute to their maintenance or elimination through successive cell cycles and phenotypic impact. The study of chromosomal mosaicism provides a natural model to characterize the effect of aneuploidy on genome stability and compare cells with the same genetic background and environment exposure, but differing in the presence of sSMC. Here, we report the functional characterization of different cell lines from two familial patients with mosaic sSMC derived from chromosome 12. We performed studies of proliferation dynamics, stability, and variability of these cells using fluorescent in situ hybridization (FISH), sister chromatid exchanges (SCE), and conventional staining. We also quantified the telomere-related genomic instability of sSMC cells using 3D telomeric profile analysis by quantitative-FISH. sSMC cells exhibited differences in the cell cycle dynamics compared to normal cells. First, the sSMC cells exhibited lower proliferation index and higher frequency of SCE than normal cells, associated with a higher level of chromosomal instability. Second, sSMC cells exhibited more telomeric-related genomic instability. Lastly, the differences of sSMC cells distribution among tissues could explain different phenotypic repercussions observed in patients. These results will help in our understanding of the sSMC stability, maintenance during cell cycle, and the cell cycle variables involved in the different phenotypic manifestations.

Genotoxicity of nedaplatin in cultured lymphocytes: modulation by vitamin E

Nedaplatin is a chemotherapeutic agent used widely in cancer therapy. Nedaplatin has been shown to cause DNA damage to cells via the induction of oxidative stress. Vitamin E (Vit E) has an anti-mutagenic activity that can protect cells from DNA damaging agents. The objective of this study is to examine the genotoxic and cytotoxic effects of nedaplatin in human cultured lymphocytes. In addition, modulation of such effects by Vit E was also examined. The frequencies of sister chromatid exchange (SCE) and chromosomal aberrations (CAs) were used as an indicator for genotoxicity. The mitotic and proliferative indices were used to examine the cytotoxic effects of nedaplatin. The results showed that nedaplatin significantly elevated SCE and CA frequencies in human lymphocytes (p ˂ 0.01). The increases in the frequencies of SCE and CA caused by nedaplatin were lowered by pretreatment treatment with Vit E (p < 0.05). Nedaplatin significantly lowered mitotic index but Vit E pretreatment did not modulate this effect. These results suggest that Vit E has the potential to ameliorate the genotoxicity of nedaplatin in cultured lymphocytes.

In vitro effects of Sunset Yellow on Chromosomal Damage and Sister Chromatid Exchanges in Human Peripheral Lymphocytes

Sunset Yellow (SY) is an organic azo dye that is used extensively as a coloring agent in many industries, such as cosmetics, pharmaceuticals ,and foodstuffs. Many studies have conflicting results about the genotoxicity effect of SY. Thus, the purpose of this study was to provide additional data concerning SY genotoxicity in human lymphocytes by using chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) assay. Four concentrations of Sunset Yellow (1, 5, 20 ,and 50 mg/ml) were used on human lymphocyte cultures. Positive and negative controls were mitomycin C and distilled water, respectively. Compared to the control, SY caused a significant increase in CAs and SCEs frequencies at all concentrations. A total of five types of CAs were observed, such as gaps, fragments, RCF, stickiness,and polyploidy. According to the present results, high concentrations of SY are genotoxic in vitro to cultured human lymphocytes. To determine its full genotoxicity potential, SY should be tested in other test systems.

Derivation of a biological limit value (BLV) for inorganic lead based on lead-induced genotoxicity in workers using the benchmark dose approach (BMD)

BackgroundSafe exposure levels for industrial chemicals are a prerequisite to the safety of workers in occupational settings. MethodsThe application areas of the benchmark dose (BMD) approach have tremendously increased in recent years. Quantitative analyzes of dose-response relationships of genotoxic chemicals are among these application areas too. This study investigates the applicability of sister chromatid exchange (SCE) frequencies in lymphocytes of lead-exposed workers to derive a biological limit value (BLV) for inorganic lead. To this end, our previously published occupational lead exposure data were pooled and re-examined by using the BMD approach. Subsequently, we determined the point of departure (POD) value for lead-induced SCE frequencies in lymphocytes. Accordingly, the blood lead concentrations and SCE frequencies in lymphocytes of 26 control and 108 lead-exposed male voluntary workers employed in a battery manufacturing plant were subjected to BMD modeling to determine the BMD confidence interval (BMD-CI). ResultsAccording to our data set, benchmark dose lower bound (BMDL) of 6.55 μg Pb/dL blood for the SCE frequencies in lymphocytes of lead-exposed workers has been obtained. ConclusionThe blood lead concentration of 6.55 μg/dL might be proposed as the BLV for lead and its inorganic lead compounds based on our dataset.

Assessment of the genotoxic potential of tetrachlorvinphos insecticide by cytokinesis-block micronucleus and sister chromatid exchange assays.

Tetrachlorvinphos is an organophosphate that is classified as a carcinogen in humans by several authorities. Due to very limited data regarding the genotoxic potential, we aimed to comprehensively investigate in vitro genotoxic potential of tetrachlorvinphos. We performed our study by applying the cytokinesis-block micronucleus cytome and sister chromatid exchange (SCE) assays to human peripheral blood lymphocytes. We evaluated micronucleus (MN) and SCE frequencies and cytokinesis-block proliferation index in both exposed and non-exposed lymphocytes. We also calculated the chromosomal instability level in response to exposure by combining the results of MN and SCE. We found that MN frequency did not increase with exposure to tetrachlorvinphos (0-50µg/ml). In contrast, we observed that SCE frequencies significantly increased with exposure to ≥5µg/ml tetrachlorvinphos. Furthermore, exposure to tetrachlorvinphos at concentrations of 50µg/ml induced a significant increase in chromosomal instability level (p < 0.05). Cytokinesis-block proliferation index level did not significantly decrease in response to tetrachlorvinphos exposure. Our findings reveal that tetrachlorvinphos resulted in different DNA damages that were measured by two assays. Furthermore, our findings suggested that exposure to tetrachlorvinphos increased chromosomal instability that is a hallmark of many malignancies. We conclude that although tetrachlorvinphos does not significantly increase the MN level, the significant increase of both SCE and CIN frequencies indicates the genotoxic potential of tetrachlorvinphos in human peripheral lymphocytes. Additionally, tetrachlorvinphos is not cytotoxic in the range of tested concentrations.

Ameliorative effect of metformin on methotrexate-induced genotoxicity: An in vitro study in human cultured lymphocytes.

Methotrexate is a folic acid antagonist that has been shown to be genotoxic to normal healthy cells. Metformin is an insulin-sensitizing agent, with multiple potential pharmacodynamic profiles. The aim of the present study was to evaluate the genotoxic effect of methotrexate on DNA and the potential ameliorative effect of metformin on chromosomal damage induced by methotrexate. The present study was performed in vitro, and the frequency of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) in human cultured lymphocytes were measured. Blood samples from five non-smoking healthy men aged 20-35 years were donated and used in the present study. Treatment of cultured blood cells with methotrexate significantly increased the number of cells with CAs (P<0.0001) and the frequency of SCEs (P<0.0001). The chromosomal injury induced by methotrexate was significantly reduced by pretreatment of the samples with metformin (P<0.0001). Importantly, the treatment of the cells with metformin alone did not affect the frequency of SCEs compared with the control group (P>0.05). Additionally, methotrexate and metformin alone, and combined, induced significant decreases in the proliferative index compared with the control group (P<0.05). In conclusion, metformin ameliorated the genotoxicity induced by methotrexate in cultured human lymphocytes.

Cytogenesis Effects on Sub-chronic administration of Cypermethrin in Albino Wistar Rats by different Mammalian Bio-assays

The cytogenotoxic effects of cypermethrin on bone marrow cells and lymphocytes of Wistar rats are reported. During four weeks of experimentation, cypermethrin admistration at 1/25th and 1/50th of LD50 by oral intubation showed a dose-dependent increase in the frequency of sister chromatid exchange (SCEs) and micro-nucleated cells. A dose dependent increase in chromosomal aberrations like fragmentation, breakage and gaps in all the treated rats was ovserved. Increased tail length of lymphocytic comets in treated rats revealed that chronic exposure of cypermethrin resulted in carcinogenic and mutagenic effects.

Cytogenetic effects of antidiabetic drug metformin

Metformin (MET) is the first-choice antidiabetic drug for type 2 diabetes mellitus treatment. In this study, the genotoxic potential of MET was evaluated by using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and micronucleus (MN) assays in human peripheral lymphocytes as well as comet assay in isolated lymphocytes. Human lymphocytes were treated with different concentrations of MET (12.5, 25, 50, 75, 100, and 125 µg/mL) for 24 h and 48 h. A negative and a positive control (Mitomycin-C-MMC, 0.20 μg/mL, for CA, SCE, and MN tests; hydrogen peroxide-H2O2, 100 µM, for comet assay) were also maintained. MET significantly increased the frequency of CAs at 48 h exposure (except 12.5 µg/mL) compared to the negative control. MET increased SCEs/cells in both treatment periods (except 12.5 µg/mL at 24 h). MET only increased the frequency of MN at 125 µg/mL. While MET significantly increased the comet tail length (CTL) at four concentrations (25, 75, 100, and 125 µg/mL), it did not affect comet tail intensity (CTI) (except 125 µg/mL) and comet tail moment (CTM) at all the treatments. All these data showed that MET had a mild genotoxic effect, especially at a long treatment period and higher concentrations in human lymphocytes in vitro. However, further in vitro and especially in vivo studies should be conducted to understand the detailed genotoxic potential of MET. Highlights Metformin increased the frequency of CAs and SCEs, especially at 48-h exposure time in human lymphocytes. This antidiabetic drug increased the frequency of MN only at the highest concentration tested (125 µg/mL). Metformin significantly increased the comet tail length in all treatments (except 50 µg/mL). The drug did not significantly affect the comet tail intensity (except 125 µg/mL) and comet tail moment in all treatments.

Structurally characterized copper-chrysin complexes display genotoxic and cytotoxic activity in human cells

The scientific interest in the development of novel anticancer metallodrugs with improved clinical efficiency and pharmacological properties based on a variety of metal ions and naturally derived products as biological ligands, is continuous and rising. Herein, we present the synthesis, full structural and physico-chemical characterization of two heteroleptic complex assemblies of Cu(II) with chrysin and the anchillary aromatic chelators 1,10-phenanthroline and 2,2́-bipyridine. The complexes constitute the only crystallographically characterized structures with Cu(II) as the metal core and flavonoid chrysin as the ligand. The frequency of sister chromatid exchanges (SCEs) was measured as an indicator of genotoxicity while the proliferation rate index (PRI) and mitotic index (MI) were estimated as indicators of cytostatic effect. In addition, cytotoxicity studies through resazurin assay were employed against two human lung cancer cell lines. Our results indicate significant cytotoxic and genotoxic activity of the novel heteroleptic Cu(II)-chrysin complexes that merit further investigation of their pharmacological profile.

Antigenotoxic and Antimutagenic Effects of Andrographis paniculata , a Traditional Medicinal Herb against Genotoxicity of Cyclophosphamide: An In Vitro Study on Human Peripheral Lymphocytes

Andrographis paniculata (family: Acanthaceae) is a medicinal herb—used in Indian system of medicine (Ayurveda, Siddha, and Unani), traditional and folk systems to treat various illnesses. This study examined the phytochemical constituents of ethanol extract from A. paniculata and its protective effect against genotoxicity caused by cyclophosphamide (CPA). Phytochemical screening and estimation of total phenolic content were analyzed using standard methods. The bioactive components from the ethanol extract of A. paniculata (EAP) were analyzed using gas chromatography-mass spectrometry. To investigate the protective effect of EAP against CPA-induced genotoxicity, human peripheral lymphocyte cultures were used. To test the antigenotoxic and antimutagenic effects of EAP, lymphocytes were treated with different concentrations of extract (50∼250 mg/mL) alone and co-treated along with CPA+EAP for 48 h. The cells were analyzed for structural chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) in control, CPA treated, and CPA+ EAP co-treated lymphocytes. Results of the study revealed that the lymphocyte cultures which had 48 h continuous exposure to EAP (50∼250 mg/mL) did not show any significant changes in CAs and SCE frequencies. These results substanti-ate the antimutagenic nature of the extract. Furthermore, the lymphocytes co-treated with CPA along with extract showed a significant reduction in CAs (reduced from 26.50±2.50% to 11.00±1.00%) and SCEs (reduced from 9.92±0.63 per cell to 4.56±0.18 per cell). These results suggest that A. paniculata is protective against CPA induced genotoxicity and put forward its possible use as a supplement with chemotherapeutic drugs.

Cytogenetic effects among workers exposed to formaldehyde. The possible role of some polymorphisms

Abstract Background Formaldehyde (FA) is a human carcinogen. It is commonly used in diluted form as formalin. The purpose of this work was to evaluate the frequencies of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) as a consequence of the exposure to FA in a hospital setting, taking into account the role of some polymorphisms in developing genotoxic damage. Methods CAs and SCEs assays were performed on peripheral blood lymphocytes of 57 pathologists enrolled in Turin hospitals (Italy) and 48 unexposed enrolled as controls. All subjects were genotyped for CYP1A1 exon 7 (A&amp;gt;G), CYP1A1*2A (T&amp;gt;C), CYP2C19*2 (G&amp;gt;A), GSTT1 (Positive/Null), GSTM1 (Positive/null), GSTP1 (A&amp;gt;G), XRCC1 (G399A), XRCC1 (C194T), XRCC1 (A280G), XPD (A751C), XPC exon 15 (A939C), XPC exon 9 (C499T), TNFα -308 (G&amp;gt;A), IL10 -1082 (G&amp;gt;A), IL10 -819 (C&amp;gt;T) and IL6 -174 (G&amp;gt;C) gene polymorphisms. Due to the little number of recessive homozygotes, we compared the dominant genotype with the combined group of heterozygotes and recessive homozygotes. Results Among pathologists, the mean value of personal air-FA was 64.2 µg/m3, mean significantly higher (p = 0.000) than controls (19.1 µg/m3). Similarly, pathologists showed significantly higher values of SCEs (p = 0.009) and CAs (p = 0.000) with respect to controls. In the same group, CYP2C19*2 (p = 0.011), XRCC1 (G399A) (p = 0.007), and IL10 (-1082) (p = 0.042) gene polymorphisms influenced the CAS levels, as well as those of CYP1A1 exon 7 (p = 0.010), XPD A751C (p = 0.002), XPC C499T (p = 0.040), and IL10 (-819) (p = 0.005) the levels of SCEs. In control group, CAs resulted significantly lower in CYP1A1 exon 7 dominant homozygotes (p = 0.001). Conclusions Our study confirms the role of FA as an inductor of genotoxicity, even when, daily, workers are exposed to low FA levels. Some genetic polymorphisms seem to have an influence in modulating the effect of FA exposure, highlighting, in occupational health studies, the role of the individual susceptibility. Key messages FA exposure is confirmed to be a genotoxicity inductor even at low concentrations. Some genetic polymorphisms seem to have a role in the modulation of FA exposure-related damage.

Occupational benzene exposure and the risk of genetic damage: a systematic review and meta-analysis

BackgroundBenzene, an important component of organic solvents, is commonly used in industry. Meanwhile, benzene is a human carcinogen leading to leukemia. Although the links between benzene and various types of genetic damage indicators have been evaluated in several studies, but their results remain inconsistent. So we conducted a meta-analysis, and to explore the influence of low concentration benzene exposure on workers’ genetic damage indicators using 3.25 mg/m3 as the boundary value, in order to provide a basis for improved prevention and control of the harm from benzene exposure to the occupational population.MethodsWe conducted a search of five databases, including Pub Med, Web of Science, China National Knowledge Infrastructure (CNKI), Wan Fang Data and Chongqing VIP, to identify relevant articles up to December 25, 2018. Two researchers independently extracted and evaluated the data according to the inclusion and exclusion criteria of the literature. The imported articles were managed by Endnote X7, and the data were extracted and sorted by Excel 2013. We utilized Stata 12.0 software to perform the meta-analysis in the present study.ResultsA total of 68 eligible articles were finally included for the synthetic analyses. The meta-analysis results showed that occupational benzene exposure led to significantly increased Micronucleus (MN) frequency, Sister chromatid exchange (SCE) frequency, Chromosome aberration (CA) frequency, Olive Tail moment (OTM), Tail moment (TM), Tail length (TL), and Tail DNA% (T DNA%) compared to the control group (P < 0.05), and the pooled effect value estimates were 1.36, 0.98, 0.76, 1.06, 0.96, 1.78, and 1.42, respectively. Subsequent analysis of the effect of low concentration benzene exposure on genetic damage found significantly increased MN frequency increased compared with the control group (P < 0.05).ConclusionsOccupational benzene exposure can affect multiple genetic damage indicators. Even at an exposure concentration lower than 3.25 mg/m3, benzene exposure has genotoxicity. These data provide an important scientific basis for the further revision of occupational disease prevention strategies. At the same time, increased attention should be focused on the health monitoring of the occupational population exposed to benzene, and health management should be strengthened to improve the health of the occupational population.

The Protective Effect of Cilostazol in Genotoxicity Induced by Methotrexate in Human Cultured Lymphocytes.

Methotrexate is an antagonist of folic acid that has been shown to be genotoxic to healthy body cells via induction of oxidative stress. Cilostazol is a phosphodiesterase III inhibitor and a potent antioxidant drug. To evaluate the potential protective effect of cilostazol on methotrexate genotoxicity. The genotoxic effect of methotrexate by measuring the frequency of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) in human cultured lymphocytes was studied. Methotrexate significantly increased the frequency of CAs and SCEs (p < 0.0001) as compared to control cultures. This chromosomal damage induced by methotrexate was considerably decreased by pretreatment of the cells with cilostazol (P < 0.01). Moreover, the results showed that methotrexate resulted in a notable reduction (P < 0.01) in cells kinetic parameters, the mitotic index (MI) and the proliferative index (PI). Similarly, cilostazol significantly reduced the mitotic index, which could be related to the anti-proliferative effect (P < 0.01). Methotrexate is genotoxic, and cilostazol could prevent the methotrexate-induced chromosomal damage with no modulation of methotrexate-induced cytotoxicity.

ORCA/LRWD1 Regulates Homologous Recombination at ALT-Telomeres by Modulating Heterochromatin Organization.

SummaryTelomeres are maintained by telomerase or in a subset of cancer cells by a homologous recombination (HR)-based mechanism, Alternative Lengthening of Telomeres (ALT). The mechanisms regulating telomere-homeostasis in ALT cells remain unclear. We report that a replication initiator protein, Origin Recognition Complex-Associated (ORCA/LRWD1), by localizing at the ALT-telomeres, modulates HR activity. ORCA's localization to the ALT-telomeres is facilitated by its interaction to SUMOylated shelterin components. The loss of ORCA in ALT-positive cells elevates the levels of two mediators of HR, RPA and RAD51, and consistent with this, we observe increased ALT-associated promyelocytic leukemia body formation and telomere sister chromatid exchange. ORCA binds to RPA and modulates the association of RPA to telomeres. Finally, the loss of ORCA causes global chromatin decondensation, including at the telomeres. Our results demonstrate that ORCA acts as an inhibitor of HR by modulating RPA binding to ssDNA and inducing chromatin compaction.

Antigenotoxic Effects of Epigallocatechin Gallate against Hair Dye Induced Genotoxicity in Cultured Human Peripheral Blood Lymphocytes

The dermal exposure of hair dye compounds i.e. p-Phenylenediamine (PPD), a primary ingredient of hair dye along with resorcinol (RE) and hydrogen peroxide (H2O2) occurs during hair dying process. Epigallocatechin gallate (EGCG) is the most abundant catechin of green tea having anticancerous properties. To determine the genotoxicity of hair dye and antigenotoxicity of EGCG, in vitro investigations were carried out using comet and sister chromatid exchange (SCE) assays on cultured human peripheral blood lymphocytes (PBLs). To reduce hair dye genotoxicity, cultured PBLs were treated with different doses of EGCG along with the hair dye. Our findings indicate that hair dye ingredients (p-Phenylenediamine-200 μg/ mL, resorcinol-200 μg/mL, and hydrogen peroxide-6.168 μg/mL) concentrations are found significantly (p<0.05) genotoxic as measured by tail moment value and SCE frequency. On the other hand, hair dye along with EGCG shows significant (p<0.05) decrease in tail moment and SCE frequency in a dose-dependent manner as compared to hair dye treated samples.

Vitamin E protects against cisplatin-induced genotoxicity in human lymphocytes

Cisplatin is an anticancer drug that is widely used in treatments of human malignancies such as ovaries,’ testes,’ and solid tumors of the head and neck. However, the use of cisplatin in the treatments can be associated with DNA damage and high risk to the development of secondary malignancies. Vitamin E is a strong lipophilic antioxidant that has the ability to protect normal cells from chromosomal damage and promote the repair of the damaged DNA. In the current study, the possible protective effect of vitamin E on DNA damage induced by cisplatin was investigated. For that, chromosomal aberrations (CAs) frequency and the number of sister chromatid exchanges (SCEs) were measured in cultured human lymphocytes. Results showed that cisplatin statistically significant increases in the number of cells with CAs (P < 0.05) and in the frequency of SCEs (P < 0.05) as compared to the control group. These increases were significantly lowered by pretreatment of cells with vitamin E. Additionally, cisplatin reduced mitotic index at used concentrations (P < 0.05), which was normalized by vitamin E. Therefore, we conclude that vitamin E can prevent the genotoxicity of cisplatin on cultured human lymphocyte.

Protective effect of extracts of Teucrium Polium and Rumex Crispus against cyclophosphamide-induced genotoxic damage in human lymphocytes

Teucrium polium (T. polium) and Rumex crispus (R. crispus) are plant species that grow widely in Anatolia and are thought to have healing effects for many diseases. In this study plant extracts are suggested as alternative agents in repairing cellular damage by using sister chromatid exchange (SCE), micronucleus (MN), mitotic index (MI), replication index (RI) and nuclear abnormalities (NAs), against the genotoxicity of cyclophosphamide (CP) in the human lymphocyte cells. 8 experimental groups were formed in the study. The cell culture medium was supplemented with 0.16 g/ml CP and the cells were treated with 50, 100 and 250 M T. polium and R. crispus extracts in the presence and absence of CP. As a result, CP significantly decreased MI frequency while increasing SCE, MN and NAs frequencies in cells. 100 M T. polium plus CP decreased SCEs when compared with CP alone. In addition, MN frequency was significantly decreased in 100 M T. poliumplus CP and 250 M R. crispus plus CP combine groups. Our results suggest that these plant extracts are not genetically damaging and have improving effects at these doses.

Assessment of genome stability in various breeds of cattle.

Chromosomal instability is a type of genome instability involving changes in genetic information at the chromosomal level. The basic tests used to identify this form of instability are sister chromatid exchange (SCE) tests and identification of fragile sites (FS). SCE is the process by which sister chromatids become fragmented as a result of DNA strand breakage and reassembly, followed by exchange of these fragments. FS can be observed in the form of breaks, gaps or constrictions on chromosomes, which often result from multiple nucleotide repeats in DNA that are difficult to replicate. The research material was the peripheral blood of ten breeds of cattle raised in Poland, including four native breeds covered by a genetic resources conservation programme, i.e. Polish Red, Polish Red-and-White, White-Backed, and Polish Black-and-White, as well as Polish Holstein-Friesian, Simmental, Montbéliarde, Jersey, Limousine and Danish Red. Two tests were performed on chromosomes obtained from in vitro cultures: SCE and FS. The average frequency of SCE was 5.08 ± 1.31, while the incidence of FS was 3.45 ± 0.94. Differences in the incidence of SCE and FS were observed between breeds. The least damage was observed in the Polish Red and White-Backed breeds, and the most in Polish Holstein-Friesians. The most damage was observed in the interstitial part of the chromosomes. Age was shown to significantly affect the incidence of SCE and FS. Younger cows showed less damage than older ones (SCE: 4.84 ± 1.25; 5.34 ± 1.24; FS: 3.10 ± 0.88, 3.80 ± 0.92).

Determination of genotoxic effects in hemodialysis patients with chronic kidney disease and the role of diabetes mellitus and other biochemical parameters

Chronic kidney disease (CKD) is a common health problem. The primary etiology of CKD is diabetes mellitus (DM). The aim of our study is to determine the possible role of DM and also effects of other factors such as hypertension, duration of hemodialysis (HD), age, sex, body mass index (BMI), and levels of hemoglobin (HB), intact parathormone (iPTH), and ferritin on genetic alterations in maintenance HD patients using chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), and micronucleus (MN) tests. According to the results, the frequency of CAs (p = 0.001), SCEs (p < 0.001) and MN (p < 0.001) statistically increased in HD patients compared to controls. However, there was no significant effect of diabetes as well as other factors on CA, SCE (except at factor of age), and MN in HD patients compared to controls. The mitotic (MI), replication (RI) and nuclear division indices (NDI) significantly decreased in HD patients compared to controls (p < 0.001). In addition, RI (p < 0.001) and NDI (p = 0.047) were significantly decreased in diabetic HD patients than the non-diabetic HD patients. There was no relation between the frequency of CA, SCE and MN and duration of HD treatment with correlation analysis. According to univariate regression analyses, only having CKD was significantly associated with the values of CA, SCE and MN. However, in multivariate analyses, only having CKD remained as significantly associated with CA, SCE and MN values. Consequently, the clastogenic and mutagenic effects increased in HD patients compared to controls; unlike DM in which cell proliferation decreased.