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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 (HepG 2 ) 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 HepG 2 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 HepG 2 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. IC 50 value was found to be a 15% for 48 h. IC 50 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.

Food additives (FAs) (flavor enhancers, sweeteners, etc.) protect foods during storage and transportation, making them attractive to consumers. Today, while the desire to access natural foods is increasing, the chemicals added to foods have started to be questioned. In this respect, genotoxicity tests have gained importance. Studies show that some food additives may have genotoxic risks. Previous studies carried out in our laboratory also revealed genotoxic effects of Monopotassium glutamate (MPG), Monosodium glutamate (MSG), Magnesium diglutamate (MDG) as flavor enhancers; Potassium benzoate (PB), Potassium sorbate (PS), Sodium benzoate (SB), Sodium sorbate (SS) as preservatives; Acesulfame potassium (ACE-K), Xylitol (XYL) as sweeteners. In this study, we determined the interactions of these food additives with ATM and p53 proteins, which are activated in the cell due to genotoxic effects, and with DNA by employing the molecular docking method for the first time. Among the food additives, SB (-4.307) for ATM, XYL (-4.629) for p53, and XYL (-4.927) for DNA showed the highest affinity. Therefore, flexible docking (IFD) scores were determined for SB, XYL, and MDG from flavor enhancers. The potential binding modes of the food additives to target molecules' possible inhibition mechanisms were determined by molecular docking. Thus, new information was obtained to show how these additives cause chromosomal abnormalities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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 H 2 O 2 ) 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 (H 2 O 2 ). 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 H 2 O 2 . 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Contrast agents have been used in magnetic resonance imaging (MRI) as a radiological method. Gadolinium-based contrast agents (GBCAs), because of their paramagnetic characteristics, are the ones mostly used in MRI to increase signal intensity. However, the use of contrast media has raised concerns on cellular toxic risks of these agents. Studies showed the accumulation of gadolinium after injection to humans with or without renal impairment. Also, there are findings obtained under in vitro and/or in vivo conditions that revealed conflicting results for their cytotoxic and genotoxic effects. Some of them declared damage in cells and genetic material; some others did not. Abnormal cell growth and genetic aberration are critical because they may lead to carcinogenesis in somatic cells or may be transferred to the next generations through germ cells. Therefore, understanding the effect of GBCAs on cells is important for their safer usage in clinical administrations to generate high-quality contrast-enhanced magnetic resonance images. Because of all these reasons, cellular toxicities-mainly genotoxic and cytotoxic effects-of GBCAs were reviewed in this paper., (© 2022 John Wiley & Sons Ltd.)

Several antioxidant food additives are added to oils, soups, sauces, chewing gum, potato chips, and so on. 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 (0.031, 0.063, 0.125, 0.25, and 0.50 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 24 h treatment. Similarly, at 48 h treatment, the frequency of SCE raised significantly compared to solvent controls at all the concentrations (except 0.031 μg/ml). An important reduction was detected in mitotic index values in the highest concentration at 24 h treatment and almost all concentrations (except 0.031 and 0.063 µg/ml) at 48 h treatment. The results obtained suggest that octyl gallate has no important genotoxicological action on human peripheral lymphocytes at the concentrations applied in this study., (© The Author(s) 2023. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society.)

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., (© 2023 Environmental Mutagenesis and Genomics Society.)

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 .

Exopolysaccharide isolated from Lactobacillus salivarius (new genus name Ligilactobacillus) KC27L strain (EPS KC27L ) exhibits antioxidant properties with 1,1-diphenyl-2-picrylhydrazase (DPPH) radical and superoxide anion radical (O 2 -. ) scavenging effect and iron ion (Fe 2+ ) chelating activity. This study aimed to investigate the in vitro genotoxic effects of EPS KC27L 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 (H 2 O 2 ; 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 EPS KC27L was investigated in the scanning electron microscope (SEM). EPS KC27L alone did not cause a significant genotoxic effect in CA, SCE, MN, and comet tests. EPS KC27L significantly decreased the frequency of CA, SCE, and MN induced by MMC and MMS. EPS KC27L also significantly reduced DNA damage induced by H 2 O 2 . This study showed that the EPS KC27L alone has no genotoxic risk at these concentrations and shows antigenotoxic activity against MMC, MMS, and H 2 O 2 . Consequently, EPS KC27L was found to exhibit chemopreventive activity against genotoxic agents. This effect is believed to be due to the antioxidant properties of EPS KC27L ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Many genotoxicity tests allow us to understand the mechanism of damages on genetic material occurring in living organisms against various physical and chemical agents. One of them is the Comet test. The current study aimed to evaluate genotoxic caused by picloram and dicamba to root meristems of Allium cepa utilizing comet assay., Methods: Two different protocols were used for rooting and auxin/pesticide application. (i) A. cepa bulbs were rooted in MS medium and then treated with Murashige and Skoog (MS) medium (control) and 0.67, 1.34, 2.01, 2.68, 3.35, 4.02, and 8.04 mg/L of picloram and dicamba using aseptic tissue culture techniques. (ii) A. cepa bulbs were then rooted in bidistilled water and treated with 0 (control), 0.67, 1.34, 2.01, 2.68, 3.35, 4.02, and 8.04 mg/L of picloram and dicamba in distilled water. The A. cepa root tip cells in both treatment groups were examined using comet test to find the possible DNA damaging effects of picloram and dicamba., Results: The results obtained at all the concentrations were statistically compared with their control groups. Almost at all the concentrations of Picloram and dicamba increased comet tail intensity (%) and tail moment in roots treated in MS medium. Two highest concentrations revealed toxic effect. On the other hand, DNA damaging effect of both auxins was only noted on the highest (> 4.02 mg/L) in roots treated in distilled water., Conclusions: This study approve and confirm genotoxic effects of how growth regulators on plants. These findings give an evidence of DNA damage in A. cepa. Therefore, both picloram and dicamba should only be used in appropriate and recommended concentrations in agriculture to conserve ecosystem and to pose minimum threat to life., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Gadobutrol and gadoversetamide are gadolinium-based contrast agents (GBCAs) widely used during magnetic resonance imaging examination. In this study, the genotoxicity of two GBCAs, gadobutrol and gadoversetamide, was investigated by using different endpoints: chromosome aberration (CAs), sister chromatid exchange (SCEs), and micronucleus (MNi). Human peripheral lymphocytes (PBLs) were treated with five concentrations (7 000, 14 000, 28 000, 56 000, and 112 000 μg/mL) of both agents. While a few concentrations of gadobutrol significantly increased abnormal cell frequency and CA/Cell, nearly all the concentrations of gadoversetamide significantly elevated the same aberrations. Similarly, the effect of gadoversetamide on the formation of SCEs was higher than those of gadobutrol. Only one concentration of gadoversetamide significantly increased MN% but no gadobutrol. The comet assay was applied for the only gadobutrol which induced a significant increase in tail intensity at the highest concentration only. On the other hand, significantly decreased mitotic index (MI) was observed following both substances, again gadoversetamide was slightly higher than those of the gadobutrol. The results revealed that both the contrast agents are likely to induce genotoxic risk in PBLs. However, different concentrations and treatment periods should be examined in vitro and specifically in vivo with different test systems for the safer usage of these contrast agents.

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-H 2 O 2 , 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.HighlightsMetformin 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.

Pullulan is a biocompatible and water-soluble exo-polysaccharide produced by primary strains of the fungus Aureobasidium pullulans. It is frequently used in the pharmaceutical and food industries. In this study, possible cytotoxic effect of pullulan was assessed using the MTT assay in the human breast cancer (MCF-7) cell line. Micronucleus (MN), micronucleus-FISH (MN-FISH), random amplified polymorphic DNA (RAPD-PCR), and comet assays were used to investigate genotoxic and antigenotoxic effects of pullulan against mitomycin C (MMC) (at MN assay) and hydrogen peroxide (at comet assay) in human lymphocytes. Antigenotoxicity was determined using two different applications: 1 h pretreatment and simultaneous treatment. In the MTT assay, pullulan significantly reduced the cell viability at 15.6-2000 μg/mL compared to the control. No significant alterations in MN rates were found in human lymphocytes treated with different concentrations of pullulan compared to the control. In contrast, co-treatment of pullulan and MMC decreased the frequency of MN in almost all the treatment concentrations and durations compared to the MMC. No significant change was observed in the frequency of the centromere-positive C + or negative C- MNi compared to the positive control. In comet assay, pullulan did not affect comet tail intensity compared to the negative control. On the contrary, pullulan in combination with H 2 O 2 significantly decreased tail intensity at almost all the concentrations compared to the positive control. The changes occurring in RAPD-PCR profiles following pullulan treatments included an increase or decrease in band intensity and gain or loss of bands. These results indicate that exopolysaccharide Pullulan is not genotoxic; moreover, it possesses a protective effect against MMC and H 2 O 2 induced genotoxicity. In breast cancer cells, pullulan induced cytotoxic/anti-proliferative effect., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Amygdalin is a cyanogenic glycoside, mainly present in the seeds of the Rosaceae family such as apricots, peaches, and bitter almond. In this study, in vitro genotoxic and antigenotoxic effects of amygdalin have been investigated on human peripheral blood lymphocytes using the comet assay. The antigenotoxic effect of amygdalin was performed against hydrogen peroxide (H 2 O 2 ) using three different treatment types (pre-, simultaneous, and post-treatment). The isolated lymphocytes were incubated with different concentrations of amygdalin (0.86-13.75 µg/ml) alone and in combination with H 2 O 2 (100 µM). The results indicated that amygdalin exhibited an antigenotoxic effect against H 2 O 2 , but it did not induce the genotoxic effect alone in tested concentrations in vitro on human lymphocytes. PRACTICAL APPLICATIONS: Amygdalin is a natural compound used in alternative medicine as an anti-cancer, antipyretic, and cough suppressant. The comet assay which is relatively simple, rapid, sensitive, and economically efficient, measures the changes in genomic stability. Assessment of amygdalin alone has no genotoxic effect on human lymphocytes. Moreover, antigenotoxicity applications (pre-, simultaneous, and post-treatments) of amygdalin significantly reduced the DNA damage induced by H 2 O 2 on isolated human lymphocytes. In conclusion, amygdalin is not genotoxic, also, it exhibited antigenotoxic activity against oxidatively damaged DNA due to its antioxidant properties on human lymphocytes., (© 2020 Wiley Periodicals LLC.)

Food additives are approved chemicals used for various purposes in foods; to provide nutritional safety, increase flavor, extend shelf life, reduce nutrient losses etc. In this study, the in vitro genotoxic effects of flavor enhancers, Monopotassium glutamate (MPG) and Magnesium diglutamate (MDG) were investigated in human peripheral blood lymphocytes by using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), cytokinesis-block micronucleus cytome (CBMN-Cyt), and comet assays. Four concentrations of MPG (125, 250, 500, and 1000 μg/mL) and MDG (93.75, 187.5, 375, and 750 μg/mL) were used. Both food additives significantly reduced mitotic index and increased the frequency of CAs at high concentrations. MPG and MDG (except 93.75 μg/mL) significantly increased SCEs/Cell in concentration-dependent manner. In the CBMN-Cyt test, both MPG and MDG increased the formation of micronucleus, nuclear buds, and nucleoplasmic bridges compared to control in a concentration-dependent manner. However, these increases were statistically significant at higher concentrations. MPG (at 500 and 1000 μg/mL) and MDG (except 93.75 μg/mL) significantly increased DNA damages observed by comet assay. It is concluded from these results that MPG and MDG have clastogenic, mutagenic, aneugenic, and cytotoxic effects, particularly at high concentrations in human lymphocytes in vitro., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Cynarin is an artichoke phytochemical that possesses a variety of pharmacological features including free-radical scavenging and antioxidant activity. The origin of artichoke species appears to be Mediterranean region. Two of these species, globe artichoke (Cynara cardunculus var. scolymus L.) and cardoon (Cynara cardunculus var. altilis DC), are widely cultivated and consumed. This vegetable, as the basis of the mediterranean diet, has been used as herbal medicine for its therapeutic effects since ancient times. Therefore, this study was performed to determine genotoxic and antigenotoxic effects of cynarin against MMC (mitomycin C) and H 2 O 2 (hydrogen peroxide) induced genomic instability using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronucleus (MN), and comet assays in human lymphocytes., Materials and Methods: Lymphocytes obtained from two healthy volunteers (1 male and 1 female) were exposed to different concentrations of cynarin (12-194 μM) alone and the combination of cynarin and MMC (0.60 μM) or cynarin and H 2 O 2 (100 μM, only for comet assay)., Results: Cynarin alone did not induce significant genotoxic effect in the CA, SCE (except 194 μM), MN, and comet assays. The combination of some concentrations of cynarin and MMC decreased the frequency of CAs, SCEs and MN induced by MMC. Furthermore, the combination of cynarin and H 2 O 2 reduced all comet parameters at all the concentrations compared to H 2 O 2 alone. While the highest concentrations of cynarin significantly decreased mitotic index (MI), the combination of cynarin and MMC increased the reduction of MI induced by MMC alone., Conclusion: All the results obtained in this study demonstrated that cynarin exhibited antigenotoxic effects rather than genotoxic effects. It is believed that cynarin can act as a potential chemo-preventive against genotoxic agents., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Enniatin A (EN-A) is a Fusarium mycotoxin which is a common contaminant in grains and especially in maize and it causes serious loss of product. The aim of this study was to investigate the cytotoxic effects using 3-(4,5-dimethylthiazolyl-2)-2,5 diphenyltetrazolium bromide (MTT) assay in human cervix carcinoma (HeLa) cell line, and genotoxic effects of EN-A using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronuclei (MN) and comet assays in human lymphocytes. The cells were treated with 0.07, 0.14, 0.29, 0.57, 1.15, 2.29, 4.59 and 9.17 μM concentrations of EN-A. It exhibited cytotoxic effects in HeLa cell lines especially when the concentrations were increased. The half-inhibitory value (IC 50 ) was determined as 1.15 μM concentration for 24 h and 0.57 μM concentration for 48 h. However, EN-A failed to affect the frequency of CAs, SCEs and MN in human lymphocytes. Only a slight increase was observed in the frequency of SCEs at 0.57 μM concentration over 48 h. The replication (RI) and nuclear division (NDI) indices were not affected. On the contrary, EN-A decreased the mitotic index (MI) significantly at all concentrations compared to the negative control and solvent control (except at 0.29 μM for 24 h, and except at 0.14, 0.29 and 0.57 μM for 48 h). Treatments over 2.29 μM showed toxic effects in human lymphocytes. EN-A significantly increased comet tail intensity (except at 0.07 and 0.57 μM) in isolated human lymphocytes. The results of this study demonstrate that EN-A has an obvious cytotoxic effect especially when the EN-A concentration was increased. In addition, EN-A could exhibit a mild genotoxic effect.

Sitagliptin is an active ingredient of antidiabetic drug used in the treatment of type 2 diabetes mellitus (T2DM). In this study, the genotoxic effects of sitagliptin were determined in human lymphocytes by using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronucleus (MN) and comet assays. 31.25-1000 μg/mL concentrations of sitagliptin were used. Sitagliptin significantly increased the frequency of CAs and SCEs at the highest concentration at 24 h treatment and all concentrations (except 250 μg/mL for CA, except 31.25 and 62.50 μg/mL for SCE) at 48 h treatment compared with solvent control (DMSO). This compound increased the MN at only the highest concentration compared with the solvent control. Mitotic index (MI) significantly decreased at the three highest concentrations of sitagliptin at 48 h treatment. However, replication (RI) and nuclear division (NDI) indices were not affected at all the treatments. Comet assay results indicated that sitagliptin significantly increased mean comet tail intensity and tail moment at only two concentrations (62.50 and 1000 μg/mL for intensity, 125 and 1000 μg/mL for tail moment), and tail length at all concentrations (except 125 and 500 μg/mL). It was concluded that higher concentration of sitagliptin had genotoxic effects in the human lymphocytes in vitro., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Trazodone and milnacipran are the active antidepressant drugs that are being used in the treatment of psychiatric disorders. In this study, the in vitro genotoxic effects of trazodone and milnacipran have been determined in human peripheral blood lymphocytes by using chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), micronuclei (MN), and comet assays. 3.13; 6.25; 12.50; 25.00; 50.00; and 75.00 μg/mL concentrations of trazodone and 2.50; 5.00; 10.00; 20.00; 30.00; and 40.00 μg/mL concentrations of milnacipran were used. Trazodone and milnacipran significantly increased the frequency of CAs and SCEs compared with the control. Both of the active ingredients raised the MN frequency in a dose-dependent manner. Mitotic index was significantly decreased, but replication and nuclear division indices were not affected at all treatments. Trazodone was statistically increased the mean comet tail intensity, tail length, and tail moment at three concentrations (6.25; 12.50; and 25.00 μg/mL) compared with control. Two highest concentrations (50 and 75 μg/mL) of trazodone were toxic in the comet assay. Milnacipran increased the comet tail intensity, tail length, and tail moment at all concentrations. It is concluded that trazodone and milnacipran have clastogenic, mutagenic, and cytotoxic effects on human lymphocytes in vitro.

The incidence of chronic kidney disease (CKD) is increasing rapidly. Diabetes mellitus (DM) is the most important cause of CKD. We studied the possible role of DM in CKD patients with respect to DNA damage, as assessed by the comet assay in 60 CKD patients (with or without DM) undergoing hemodialysis and in 26 controls. Effects of other factors, such as age, sex, hypertension, duration of hemodialysis, body mass index (BMI), and levels of hemoglobin (HB), intact parathormone (iPTH), and ferritin (FER), were also examined. Primary DNA damage measured by the comet assay was significantly higher in CKD patients than in controls. Among CKD patients, the following correlations were observed. (1) There was no difference in comet tail length or tail intensity between diabetic and non-diabetic individuals. (2) Age, sex, hemoglobin, hypertension, duration of hemodialysis, and ferritin levels affected neither tail length nor intensity. (3) BMI values above 25kg/m(2) and iPTH levels above 300pg/ml were associated with significantly greater comet tail length. Our results indicate that primary DNA damage is increased in CKD patients undergoing hemodialysis, compared to controls; however, DM had no additional effect., (Copyright © 2016. Published by Elsevier B.V.)

Antitumor agents are used in therapy against many forms of human cancer. One of these is mitomycin-C (MMC). As with many agents, it can interact with biological molecules and can induce genetic hazards in non-tumor cells. One of the possible approaches to protect DNA from this damage is to supply antioxidants that can remove free radicals produced by antitumor agents. Lipoic acid (LA) is known as one of the most powerful antioxidants. The aim of this study was to investigate antigenotoxic effects of LA against MMC induced chromosomal aberrations (CA), sister chromatid exchanges (SCE) and micronucleus (MN) formation in human lymphocytes. Lymphocytes were treated with 0.2 μg MMC/heparinized mL for 48 h. Three different concentrations (0.5, 1, 2 μg/mL) of LA were used together with MMC in three different applications; 1 h pre-treatment, simultaneous treatment and 1 h post-treatment. A negative, a positive and a solvent control were also included. In all the cultures treated with MMC + LA, the frequency of abnormal cells and CA/cell significantly decreased compared to MMC. Statistically significant reduction was also observed in SCE/cell and MN frequencies in all treatments. These results demonstrated anticlastogenic and antimutagenic effects of LA against MMC induced genotoxicity. LA showed the most efficient effect during 1 h pretreatment. On the other hand, MMC + LA treatments induced significant reduction in mitotic index than that of MMC treatment alone. These results are encouraging that LA can be a possible chemopreventive agent in tumorigenesis in both cancer patients and in health care persons handling anti-cancer drugs.