Frequency Of Sister Chromatid Exchanges Research Articles

Safety assessment of high fructose corn syrup and fructose used as sweeteners in foods

High Fructose Corn Syrup (HFCS) and Fructose (FR) are widely used sweeteners in many foods and beverages. This study aimed at investigating the cytotoxic effects of HFCS (5%–30%) and FR (62.5–2000 μg/mL) using MTT assay in Human Hepatocellular Carcinoma (HepG2) cells, and genotoxic effects of using Chromosome Aberrations (CAs), Sister Chromatid Exchanges (SCEs), Micronuclei (MN) and comet assays in human lymphocytes. HFCS significantly reduced the cell viability in HepG2 cells at between 7.5% and 30% for 24 and 48 h. 30% HFCS caused a very significant toxic effect. FR had a cytotoxic effect in HepG2 cells at all treatments. However, as fructose concentration decreased, the cell viability decreased. HFCS (10%–20%) and FR (250–2000 μg/mL) decreased the mitotic index at higher concentrations. IC50 value was found to be a 15% for 48 h. IC50 value of FR was detected as 62.5 μg/mL for 24 h and 48 h. HFCS significantly increased CAs frequency at 15% and 20%. FR significantly increased the frequency of CAs at 250, 1000, and 2000 μg/mL for 48 h. Both sweeteners increased the frequency of SCEs at all concentrations. HFCS (15% and 20%) and FR (250, 1000, and 2000 μg/mL) induced MN frequency at higher concentrations. HFCS caused DNA damage in comet assay at 10% −30%. FR increased tail intensity and moment at 125-2000 μg/mL and tail length at 62.5, 250 and 500 μg/mL. Therefore, HFCS and FR are clearly seen to be cytotoxic and genotoxic, especially at higher concentrations.

Vitamin B12 Protects Against Genotoxicity Induced by Cisplatin.

Cisplatin is an effective synthetic chemotherapeutic drug used for cancer treatment. Vitamin B12 has been shown to possess anti-genotoxic activity. This study aimed to investigate the effect of vitamin B12 on chromosomal damage induced by cisplatin. The level of sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) were measured in cultured human blood lymphocytes treated with cisplatin and/or vitamin B12. The results showed a significantly elevated frequency of CAs and SCEs of cisplatin-treated cultures compared to the control (P < 0.05). The CAs and SCEs induced by cisplatin were significantly lowered by pretreatment of cell cultures with vitamin B12. In addition, cisplatin caused a slight reduction in the mitotic index (MI), while vitamin B12 did not modulate the effect of cisplatin on MI. Vitamin B12 can protect human lymphocytes against genotoxicity associated with cisplatin.

Strawberry (Fragaria × ananassa) and Kiwifruit (Actinidia deliciosa) Extracts as Potential Radioprotective Agents: Relation to Their Phytochemical Composition and Antioxidant Capacity

Ionising radiation is an important form of treatment for human cancer; however, the side effects associated with oxidative damage caused by radiation compromise its effectiveness. This work aimed to quantify the major bioactive components of freeze-dried kiwifruit (KD) and strawberry (SD) extracts and assess their potential efficacy as radioprotective agents in human blood lymphocytes. Their possible genotoxic and cytotoxic effects were also evaluated. The study was conducted by pre-treating human lymphocytes with KD and SD (50, 400, and 800 µg/mL) before radiation at 2 Gy. The results showed that SD presented a higher antioxidant capacity (12.6 mmol Trolox equivalents/100 g db) and higher values of total phenolic compounds (2435 mg of gallic acid equivalents/100 g db), while KD had the highest vitamin C content (322 mg ascorbic acid/100 g db). Regarding phenolic compounds, pelargonidin-3-glucoside was the most abundant in SD (1439 mg/1000 g db) and quercetin-3-O-galactoside in KD (635 mg/1000 g db). None of the tested concentrations of both fruit extracts showed a genotoxic effect. SD (800 µg/mL) reduced the sister chromatid exchange frequency and mitotic index. The efficacy of KD (400 and 800 µg/mL) in lowering the dicentric chromosome frequency demonstrated its radioprotective activity.

A study on Amygdalin's Genotoxicological Safety and Modulatory Activity in Human Peripheral Lymphocytes in vitro.

Amygdalin (AMY), a plant secondary metabolite containing nitrile, is a major component of the seeds of Rosaceae family plants. It is known that this compound has many pharmacological activities such as cancer prevention, antipyretic, and cough suppressant. In this study, the genotoxic and modulatory effects of amygdalin were assessed by chromosomal aberration (CA), sister chromatid exchange (SCE), and cytokinesis-block micronucleus assay (CBMN) assays using human peripheral lymphocytes (HPLs) in the absence and presence of metabolic activator (S9 mix). Lymphocytes were exposed to various concentrations of amygdalin (0.86, 1.72, 3.43, 6.86, and 13.75 μg/mL) alone and in combination with mitomycin-C (MMC, 0.20 μg/mL) or cyclophosphamide (CP, 12 μg/mL). The mitotic index (MI), replication index (RI), cytokinesis-block proliferation index (CBPI), and cytostasis were also evaluated to determine cytotoxicity. Amygdalin alone did not exhibit genotoxic and cytotoxic effects at all the tested concentrations both in the absence and presence of the S9 mix. In contrast, amygdalin significantly reduced the frequencies of CA (especially at 48 h treatments), SCE, and MN (except 0.86 μg/mL in pre- and simultaneous treatment) induced by MMC in all the tested concentrations and treatment protocols. It has also considerably decreased CP-induced CA and SCE frequencies at all the concentrations (except 0.86 μg/mL) in simultaneous treatment. This study demonstrated that amygdalin alone was not genotoxic, on the contrary, it has revealed modulatory effects against chemotherapy agents that induced genomic damage in human lymphocytes, suggesting its chemopreventive potential. This article is protected by copyright. All rights reserved.

Antigenotoxic effect of hyperoside against Mitomycin C and hydrogen peroxide-induced genotoxic damage on human lymphocytes

Hyperoside is a flavonol glycoside isolated from various plant genera such as Hypericum and Crataegus. It has an important place in the human diet and is used medically to relieve pain and ameliorate cardiovascular functions. However, a comprehensive profile of the genotoxic and antigenotoxic effects of hyperoside is not known. The current study aimed to investigate the genotoxic and antigenotoxic effects of hyperoside against genetic damages induced by two genotoxins (MMC and H2O2) using chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), and micronucleus (MN) assays in human peripheral blood lymphocytes in vitro. Blood lymphocytes were incubated with 7.8–62.5 μg/mL concentrations of hyperoside alone and simultaneously with 0.20 μg/mL Mitomycin C (MMC) or 100 μM Hydrogen peroxide (H2O2). Hyperoside did not exhibit genotoxic potential in the CA, SCE, and MN assays. Moreover, it did not cause a decrease in mitotic index (MI) which is an indicator of cytotoxicity. On the other hand, hyperoside significantly decreased CA, SCE, and MN (except for MMC treatment) frequencies induced by MMC and H2O2. Hyperoside, increased mitotic index against both mutagenic agents at 24-h treatment when compared to positive control. Our results demonstrate that hyperoside exhibited antigenotoxic effects rather than genotoxic in vitro human lymphocytes. Therefore, hyperoside may be a potential preventive agent in inhibiting chromosomal and oxidative damage induced by genotoxic chemicals.

The meta-analysis of cytogenetic biomarkers as an assessment of occupational risk for healthcare workers exposed to antineoplastic drugs.

Antineoplastic drugs (ADs) are widely used in clinical practice and have been demonstrated to be effective in treating malignant tumors. However, they carry a risk of cytogenotoxicity for healthcare workers. Studies have reported that genotoxic biomarkers can be applied to assess the occupational health status of healthcare workers at an early stage, but results of different studies are variable. The objectives of the review were examine the association between long-term exposure to ADs and cytogenetic damage to healthcare workers. We systematically reviewed studies between 2005 and 2021 using PubMed, Embase and Web of Science databases that used cytogenetic biomarkers to assess occupational exposure to ADs in healthcare workers. We used RevMan5.4 to analyze the tail length parameters of the DNA, frequency of the chromosomal aberrations, sister chromatid exchanges and micronuclei. A total of 16 studies were included in our study. The studies evaluate the quality of the literature through the Agency for Healthcare Research and Quality. The results revealed that under the random-effects model, the estimated standard deviation was 2.37 (95% confidence interval [CI] 0.92-3.81, P = 0.001) for the tail length parameters of the DNA, 1.48 (95% CI 0.71-2.25, P = 0.0002) for the frequency of chromosomal aberrations, 1.74 (95% CI 0.49-2.99, P = 0.006) for the frequency of sister chromatid exchanges and 1.64 (95% CI 0.83-2.45, P < 0.0001) for the frequency of micronuclei. The results indicate that there is a significant association between occupational exposure to ADs and cytogenetic damage, to which healthcare workers should be alerted.

Reduction of Genotoxicity of Carbamazepine to Human Lymphocytes by Pre-treatment with Vitamin B12.

Carbamazepine (CBZ) is widely used as an anti-epileptic drug. Vitamin B12 has been shown to protect against DNA damage caused by several mutagenic agents. This study aimed to investigate the effect of vitamin B12 on CBZ-induced genotoxicity in cultured human lymphocytes. Sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) genotoxic assays were utilized to achieve the study objective. The results showed significantly higher frequencies of CAs and SCEs in the CBZ-treated cultures (12 μg/mL) compared to the control group (P<0.01). The genotoxic effects of CBZ were reduced by pre-treatment of cultures with vitamin B12 (13.5μg/ml, P<0.05). Neither CBZ nor vitamin B-12 showed any effects on mitotic and proliferative indices. CBZ is genotoxic to lymphocyte cells, and this genotoxicity can be reduced by vitamin B12.

Investigation Of Genotoxic Effect Of Octyl Gallate Used As An Antioxidant Food Additive In In Vitro Test Systems.

Several antioxidant food additives are added to oils, soups, sauces, chewing gum, potato chips etc. One of them is octyl gallate. The purpose of this study was to evaluate the potential genotoxicity of octyl gallate in human lymphocytes, using in vitro chromosomal abnormalities (CA), sister chromatid exchange (SCE), cytokinesis block micronucleus cytome (CBMN-Cyt), micronucleus-FISH (MN-FISH), and comet tests. Different concentrations (0.50, 0.25, 0.125, 0.063, and 0.031 μg/mL) of octyl gallate were used. A negative (distilled water), a positive (0.20 μg/mL Mitomycin-C), and a solvent control (8.77 μL/mL ethanol) were also applied for each treatment. Octyl gallate did not cause changes in chromosomal abnormalities, micronucleus, nuclear bud (NBUD) and nucleoplasmic bridge (NPB) frequency. Similarly, there was no significant difference in DNA damage (comet assay), percentage of centromere positive and negative cells (MN-FISH test) compared to the solvent control. Moreover, octyl gallate did not affect replication and nuclear division index. On the other hand, it significantly increased the SCE/cell ratio in three highest concentrations compared to solvent control at 24h treatment. Similarly, at 48h treatment, the frequency of SCE raised significantly compared to solvent controls at all the concentrations (except 0.031 μg/mL). An important reduce was detected in mitotic index values in highest concentration at 24h treatment and almost all concentrations (except 0.031 and 0.063 µg / mL) at 48h treatment. The results obtained suggest that octyl gallate has no an important genotoxicological action on human peripheral lymphocytes at the concentrations applied in this study.

Exploring the Relationship between Spontaneous Sister Chromatid Exchange and Genome Instability in Two Cryptic Species of Non-Human Primates.

There are extensive studies on chromosome morphology and karyotype diversity in primates, yet we still lack insight into genomic instability as a key factor underlying the enormous interspecies chromosomal variability and its potential contribution to evolutionary dynamics. In this sense, the assessment of spontaneous sister chromatid exchange (SCE) frequencies represents a powerful tool for evaluating genome stability. Here, we employed G-banding, fluorescence plus Giemsa (FPG), and chromosome orientation fluorescence in situ hybridization (CO-FISH) methodologies to characterize both chromosome-specific frequencies of spontaneously occurring SCE throughout the genome (G-SCE) and telomere-specific SCE (T-SCE). We analyzed primary fibroblast cultures from two male species of Ateles living in captivity: Ateles paniscus (APA) and Ateles chamek (ACH). High frequencies of G-SCEs were observed in both species. Interestingly, G-SCEs clustered on evolutionary relevant chromosome pairs: ACH chromosomes 1, 2, 3, 4, and 7, and APA chromosomes 1, 2, 3, 4/12, 7, and 10. Furthermore, a statistically significant difference between the observed and expected G-SCE frequencies, not correlated with chromosome size, was also detected. CO-FISH analyses revealed the presence of telomere-specific recombination events in both species, which included T-SCE, as well as interstitial telomere signals and telomere duplications, with APA chromosomes displaying higher frequencies, compared to ACH. Our analyses support the hypothesis that regions of Ateles chromosomes susceptible to recombination events are fragile sites and evolutionary hot spots. Thus, we propose SCE analyses as a valuable indicator of genome instability in non-human primates.

Intellectual disability and abnormal cortical neuron phenotypes in patients with Bloom syndrome.

Bloom syndrome (BS) is a rare autosomal recessive disorder characterized by genomic instability that leads to various complications, including cancer. Given the low prevalence of BS in Japan, we conducted a nationwide survey. We recruited eight patients with BS, three of whom exhibited intellectual disability. The 631delCAA mutation in the BLM gene was detected in 9 out of 16 alleles. To investigate neuronal development in patients with BS, we generated induced pluripotent stem cells derived from one of these patients (BS-iPSCs). We examined the phenotypes of the induced cortical neurons derived from the generated BS-iPSCs using a previously reported protocol; the generated BS-iPSCs showed an approximately 10-times higher frequency of sister-chromatid exchange (SCE) than the control iPSCs. Immunocytochemistry revealed shorter axons and higher proliferative potential in BS-iPSC-derived cortical neurons compared with control iPSCs. To our knowledge, our study is the first to clarify the abnormality of the cortical neuron phenotypes derived from patients with BS. Our findings may help identify the pathogenesis of neuronal differentiation in BS and aid in the development of novel therapeutic agents.

XRCC8 mutation causes hypersensitivity to PARP inhibition without Homologous recombination repair deficiency

PARP inhibitors inflict severe toxicity to homologous recombination (HR) repair deficient cells because DNA damages induced by PARP inhibition result in lethal DNA double strand breaks in the absence of HR repair during DNA replication. PARP inhibitors are the first clinically approved drugs designed for synthetic lethality. The synthetic lethal interaction of PARP inhibitors is not limited to HR repair deficient cells. We investigated radiosensitive mutants isolated from Chinese hamster lung origin V79 cells to identify novel synthetic lethal targets in the context of PARP inhibition. HR repair deficient BRCA2 mutant cells were used for positive control. Among tested cells, XRCC8 mutants presented hypersensitivity to PARP inhibitor, Olaparib. XRCC8 mutants showed elevated sensitivity to bleomycin and camptothecin similar to BRCA2 mutants. XRCC8 mutants presented an elevation of γ-H2AX foci formation frequency and S-phase dependent chromosome aberrations with Olaparib treatment. Enumerated damage foci following Olaparib treatment were observed to be elevated in XRCC8 as in BRCA2 mutants. Although this may suggest that XRCC8 plays a role in a similar DNA repair pathway as BRCA2 in HR repair, XRCC8 mutants presented functional HR repair including proper Rad51 foci formation and even elevated sister chromatid exchange frequencies with PARP inhibitor treatment. For comparison, RAD51 foci formation was suppressed in HR repair deficient BRCA2 mutants. Additionally, XRCC8 mutants did not display delayed mitotic entry with PARP inhibitors whereas BRCA2 mutants did. XRCC8 mutant cell line has previously been reported as possessing a mutation in the ATM gene. XRCC8 mutants displayed maximum cytotoxicity to ATM inhibitor among tested mutants and wild type cells. Furthermore, the ATM inhibitor sensitized XRCC8 mutant to ionzing radiation, however, XRCC8 mutant V-G8 expressed reduced levels of ATM protein. The gene responsible for XRCC8 phenotype may not be ATM but highly associated with ATM functions. These results suggest that XRCC8 mutation is a target for PARP inhibitor-induced synthetic lethality in HR repair independent manner via the disruption of cell cycle regulation. Our findings expand the potential application of PARP inhibitors in tumors lacking DNA damage responding genes other than HR repair, and further investigation of XRCC8 may contribute to this research.

Valuating of sister chromatid exchange (SCE) in patients with type 2 diabetes mellitus

This study was established to test the cytogenetic parameter of sister chromatid exchange (SCE) in type 2 diabetic patients for its close relationship with mutations. In this study, cytogenetic analyses were done on peripheral blood lymphocytes obtained from 25 type 2 DM patients using short-term lymphocyte culture .Human lymphocytes have long been used to assess the gene damage occurring in vivo as well as in vitro. Results showed significant high frequencies of SCEs were scored in type 2 DM patients [2.25±0.08SCE/cell] compared with control [1.28±0.04SCE/cell] (P&lt;0.01). We concluded that the DM patients have significantly more genetic damage (high SCE frequency), and there are no significant differences in diabetic patients in relation with demographic characteristics (age and gender).

Cytidine deaminase deficiency in mice enhances genetic instability but limits the number of chemically induced colon tumors

Cytidine deaminase (CDA) catalyzes the deamination of cytidine (C) and deoxycytidine (dC) to uridine and deoxyuridine, respectively. We recently showed that CDA deficiency leads to genomic instability, a hallmark of cancers. We therefore investigated whether constitutive CDA inactivation conferred a predisposition to cancer development. We developed a novel mouse model of Cda deficiency by generating Cda-knockout mice. Cda+/+ and Cda−/− mice did not differ in lifetime phenotypic or behavioral characteristics, or in the frequency or type of spontaneous cancers. However, the frequency of chemically induced tumors in the colon was significantly lower in Cda−/− mice. An analysis of primary kidney cells from Cda−/− mice revealed an excess of C and dC associated with significantly higher frequencies of sister chromatid exchange and ultrafine anaphase bridges and lower Parp-1 activity than in Cda+/+ cells. Our results suggest that, despite inducing genetic instability, an absence of Cda limits the number of chemically induced tumors. These results raise questions about whether a decrease in basal Parp-1 activity can protect against inflammation-driven tumorigenesis; we discuss our findings in light of published data for the Parp-1-deficient mouse model.

Evaluation of sister chromatid exchange in patients with breast cancer in relation to clinical stage

High levels of sister chromtid exchanges (SCE) in patients with breast caner reflects a genomic instability that may be operative in carcinogenesis.The frequency of sister chromatid exchanges in peripheral blood lymphocytes was analyzed in patients with breast cancer in relation to clinical stage in 12 stage II and 5 Stage IV untreated breast cancer patients.Moreover,SCE baseline values in patients were compared with a control group of 12 healthy women. A significant difference emerged between patients and control (P&lt;0.01).SCE increased significantly in stage IV breast cancer patients compared with those patients of stage II (P&lt;0.05).The results reveal that SCE frequency increases with the progression of clinical stage of breast cancer.

Evaluation the Effect of Topiramate on the Induction Genotoxicity in Obesity Patients

Topiramate ( sulfamate - substituted monosaccharide) a weight loss drug used a pharmacotherapeutic agent for obesity , a study was performed to evaluate the effect of the topiramate to induce chromosome aberrations (CA) and sister chromatid exchange (SCE) in lymphocytes of obesity patients . CA and SCE, a sensitive measure of chromosome damage , were counted in peripheral blood lymphocytes from 32 obesity patients treated with topiramate dose ( 6 months with 81mg/day , 12 months with 129 mg/day) and 16 healthy person as control group who had never received topiramate and other drugs during the period of the study. All of the treated patients with topiramate ,have cells with CA and abnormal SCE frequencies, in analysis ,obesity patients, was significantly increased CA in 129mg/day and 81mg/day topiramate dose compared with control ( 4.08±1.51 and 3.56±1.21 ) respectively, vs (1.40± 0.81),(P&lt;0.01).Furthermore, a significantly higher SCE/Cell frequency (10.42 ±0.75and 8.75±0.38) in treated obesity patients with 129 mg/day ,81mg/day dose respectively comparison with their control group (5.91±0.31), (P&lt;0.001).&#x0D; The chromosome damage and genotoxics are related to the daily dose and may be determined by the duration of treatment .We conclude the patients treatment with topiramate may be associated with genetic toxicity according to byproducts of drug metabolism.

In vitro genotoxic and antigenotoxic effects of an exopolysaccharide isolated from Lactobacillus salivarius KC27L

Exopolysaccharide isolated from Lactobacillus salivarius (new genus name Ligilactobacillus) KC27L strain (EPSKC27L) exhibits antioxidant properties with 1,1-diphenyl-2-picrylhydrazase (DPPH) radical and superoxide anion radical (O2-.) scavenging effect and iron ion (Fe2+) chelating activity. This study aimed to investigate the in vitro genotoxic effects of EPSKC27L alone (12.50, 25.00, 50.00, and 100.00 μg/mL) and its antigenotoxic activity against DNA damage induced by mitomycin-C (MMC; 0.20 μg/mL), methyl methanesulfonate (MMS; 5.00 μg/mL), and hydrogen peroxide (H2O2; 100 μM). For this purpose, chromosome aberration (CA), sister chromatid exchange (SCE), micronucleus (MN), and comet assays were performed in human peripheral lymphocytes. In addition, the structure of EPSKC27L was investigated in the scanning electron microscope (SEM). EPSKC27L alone did not cause a significant genotoxic effect in CA, SCE, MN, and comet tests. EPSKC27L significantly decreased the frequency of CA, SCE, and MN induced by MMC and MMS. EPSKC27L also significantly reduced DNA damage induced by H2O2. This study showed that the EPSKC27L alone has no genotoxic risk at these concentrations and shows antigenotoxic activity against MMC, MMS, and H2O2. Consequently, EPSKC27L was found to exhibit chemopreventive activity against genotoxic agents. This effect is believed to be due to the antioxidant properties of EPSKC27L.

Mutagenic effect of the sex reversal hormone Diethylstilbestrol in the Nile tilapia (Oreochromis niloticus, L) through sister chromatid exchange analysis

The current study was conducted to explore the mutagenic effect of DES hormone on the treated Nile tilapia chromosomes using sister chromatid exchange (SCE) analysis. Two concentrations of DES hormone (100mg DES/kg and 200mg DES/kg diet) were addressed. The fry were fed for 60 days at 15% of the body weight daily. Two cell replication cycles, in the presence of 5-bromodeoxyuridine (BrdU) were achieved, and intestine tissues were used for chromosomes preparation. For slide staining, acridine orange (AO) was added, and the fluorescent microscope was used to the observation of AO fluorescence of stained slides. The obtained results indicated that the frequency of SCEs per cell and the percentage of cells exhibiting three SCEs per cell increased with the increasing hormone concentration. The present findings confirmed the mutagenic effect of DES hormone and clarified the possibility of using O. niloticus as an in vivo system for detecting mutagenic and carcinogenic chemicals. In addition, it is recommended not to use the hormone directly in the food served to humans. However, it can be used in the induction of fish sex inversion to XY females and followed by progeny testing, to generate super male YY.

Genotoxicity of Glyphosate on Cultured Human Lymphocytes.

Glyphosate-based herbicides are the most used herbicides in the world. Despite being widely used, a dispute exists whether glyphosate-based herbicides have a negative effect on human health, particularly genotoxic effects. Therefore, the aim of this study was to investigate glyphosate genotoxicity on cultured human lymphocytes. Cultured human lymphocytes were treated with different concentrations of glyphosate (20, 40, and 200µmol/L). Four toxicity measures were examined: frequency of chromosomal aberrations (CAs), frequency of sister-chromatid exchange (SCE), production of 8-OHdG, and cell kinetics analysis. The results show that glyphosate induced significant (P < 0.05) increases in the levels of SCE at the highest used concentration (200μmol/L). However, no significant elevation in SCE levels was observed at the lower examined concentrations (20 and 40μmol/L). No significant changes in CA were detected at all examined concentrations (P = 0.86). Also, glyphosate did not induce changes to the normal level of 8-OHdG at all examined concentrations (P = 0.98). Last, no significant changes in either mitotic index or proliferative index were observed at any examined concentrations (P > 0.05). The results collectively indicate a lack of genotoxicity and cytotoxicity of glyphosate in cultured human lymphocytes when dealing with environmentally relevant concentrations (20 and 40μmol/L). However, being exposed to higher concentrations (200μmol/L) led to slightly higher level of SCE. Therefore, we recommend cautionary measures when dealing with glyphosate-based herbicides for individuals, such as farmers, who may be extensively exposed to high concentrations of these herbicides.

The formation of SCEs as an effect of occupational exposure to formaldehyde

Formaldehyde (FA) is a ubiquitous toxic chemical employed worldwide due to its disinfectant and preservative properties. Despite being classified as a human carcinogen, FA is still employed as formalin in pathology wards as standard fixative. We evaluated its relationship with the formation of sister-chromatid exchanges (SCEs) in cultured peripheral blood lymphocytes on 57 pathologists and 48 controls and the risk/protective role played by several genetic polymorphisms. All subjects were assessed for SCEs and genotyped for the most common cancer-associated gene polymorphisms: CYP1A1 exon 7 (A > G), CYP1A1*2A (T > C), CYP2C19*2 (G > A), GSTT1 (presence/absence), GSTM1 (presence/absence), GSTP1 (A > G), XRCC1 (G399A), XRCC1 (C194T), XRCC1 (A280G), XPC exon 15 (A939C), XPC exon 9 (C499T), TNFα − 308 G > A), IL10 − 1082 (G > A), and IL6 − 174 (G > C). Air-FA concentration was assessed through passive personal samplers. Pathologists, exposed to 55.2 μg/m3 of air-FA, showed a significantly higher SCEs frequency than controls, exposed, respectively, to 18.4 μg/m3. Air-FA was directly correlated with SCEs frequency and inversely with the replication index (RI). Regression models showed FA exposure as a significant predictor in developing SCEs, while did not highlight any role of the selected polymorphisms. Our study confirms the role of low air-FA levels as genotoxicity inductor, highlighting the importance to define exposure limits that could be safer for exposed workers.

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.