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Commiphora myrrha, located in the tropical zone, is a widely used tree for medicinal purposes in the Arabian Peninsula and a large part of Africa. In this research, cytogenotoxic effects of the commercially available Commiphora myrrha essential oil (myrrh) were studied using micronucleus (MN), comet, and total oxidant (TOS), and total antioxidant (TAS) assays on human peripheral lymphocytes under in vitro conditions. In addition, pure pBR322 plasmid DNA was used to investigate DNA damaging/protecting activity of the essential oil. Finally, a bacterial reversion (Ames) test was performed using Salmonella typhimurium mutant strains TA98 and TA100 to determine the potential effect of the agent in the induction of gene mutations. The high concentration of Commiphora myrrha (0.125 mu L/mL) induced MN formation significantly compared to the untreated control in both treatment times (24 or 48 h). Only at the highest concentration, nuclear division index (NDI) values were found lower than the controls. In the Comet test performed on healthy lymphocytes, only the highest concentration of myrrh caused significant increases in the percentage of damaged cells and genetic damage index (GDI) values. Myrrh oil showed no significant mutagenic effect on mutant Salmonella strains. In addition, the substance did not directly damage plasmid DNA but also protected DNA against damaging factors such as H2O2 and UV. Finally, in the TAS and TOS assays, no significant differences on the oxidative stress parameters were found in cell culture compared to the control. The results of this study showed that myrrh oil exerts cytogenotoxic risk only at higher concentrations.

According to the evolutionary perspective, an organism must manage and optimize organized complexity effectively to achieve a strong adaptation. Within the scope of sustainable homeostasis, the subcellular components of the organism must strictly comply with the principle of minimum error and maximum efficiency in coordination. Advanced defense systems are evolution’s greatest gift to the cell. One of the most important components of cellular defense systems is the antioxidant defense. When it comes to antioxidant defense, the first thing that comes to mind is the peroxisome organelle, because the peroxisome is a cytoplasmic organelle surrounded by a single membrane in which the very important enzyme, catalase, is localized. Furthermore, the role of this organelle in vital processes, such as lipid metabolism, antimicrobial defense, and intracellular signaling, is undeniable. In this chapter, attention has been tried on the mysteries related to peroxisome by performing a wide literature review. The chapter covers topics such as peroxisome production, targeted protein transport, roles in the oxidative mechanism, relationship with diseases, and mitochondria interaction. This chapter, which highlights the polygenic formation and pleiotropic features of peroxisome, will provide an important future projection for curious researchers and medical doctors seeking innovative treatment strategies.

Patent Blue V (PBV) is a water-soluble synthetic dyestuff that is used as a coloring agent in the food industry and for medical imaging in health monitoring. The aim of this study was to investigat...

Titanium dioxide (TiO2) nanoparticles (NPs) are widely used in industry, pharmacy, medicine, and food sectors. Therefore, this study deals with the effects of TiO2 NPs in female rats following oral...

Rhus coriaria has been important in the treatment of many diseases in traditional use. In this content, the genotoxic, antigenotoxic, and oxidative stress effects of methanol extract of R. coriaria (RCE) were investigated in this study. Two hundred fifty, 500, or 750 µg/mL concentrations of RCE were not found to have DNA damaging effect on pET22-b(+) plasmid and were unable to induce micronuclei in human lymphocytes (24 or 48 h treatment period). However, it did not inhibit the genotoxic effect of mitomycin-c (0.25 µg/mL). Cytotoxic effects of RCE were investigated using mitotic index (MI) and nuclear division index (NDI). Five hundred, 1000, and 2000 mg/kg concentrations of RCE did not induce chromosome aberrations in rat bone marrow cells for 12 or 24 h treatment period. In addition, 2000 mg/kg concentration of RCE showed an antigenotoxic effect by decreasing to genotoxic effect of 400 mg/kg urethane at 12 and 24 h treatment periods. RCE showed cytotoxic effects by significantly decreasing NDI. Moreover, RCE increased cytotoxic effect of Mitomycin C (MMC). However, RCE did not induce cytotoxicity in rat bone marrow cells. The highest concentration of RCE reduced total oxidant level in 12 h treatment. Interestingly, the lowest total oxidant level was found in rats blood treated with the lowest concentration RCE and urethane together. Thousand and 2000 mg/kg concentrations of RCE decreased total antioxidant levels of rat blood at 24 h treatment period. Our results showed that RCE possess cytotoxic effect in short-term treatments in vitro. However, it does not demonstrate genotoxic or cytotoxic effects in vivo. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

Alzheimer's disease (AD) is the most common type of dementia worldwide, involving a multifactorial combination of environmental, genetic and epigenetic factors. It is characterized by the accumulation of abnormal amyloid beta (Aß) and tau fibrillar tangles, oxidative stress, neuroinflammation, and disruption of autophagy mechanisms. The agents used for the treatment of the disease only prevent the symptoms of the disease. Epigenetic modifications such as DNA methylations and histone modifications that occur in learning and memory processes have come to the fore in the search for new and reliable potential therapeutic agents for AD. Against these multiple mechanisms of AD, natural products are currently considered an alternative strategy for the discovery of new multipotent drugs. Phytocompounds of Gentiana olivieri, Gentiopicroside and Isoorientin, which have been known to have many benefits for health, act as a neuroprotective effect by acting as an anti-inflammatory and antioxidant. Based on this, in order to determine the possible effects of Gentiopicroside and Isoorientin phytocompounds on Sirtüin-1 (SIRT1), Sirtüin-2 (SIRT2), Sestrin 2 (SESN2), Histone deacetyl transferase-6 (HDAC6) and divalent metal transporter 1 (DMT1) enzymes, which are seen as targets in AD, molecular docking analysis was carried out. AutoDock 4.0 software was used to predict the interaction of ligands with possible active binding sites on the target molecule crystal structure. As a result of the analyzes, the best coupling occurred between the Gentiopicroside and DMT1 and HDAC6 enzymes. In the light of this information, it can be suggested that the molecular clamping analysis is carried out by the neuroprotective effect of Gentiopicroside by DMT1 enzyme inhibition, while Izoorientine performs through the HDAC6 enzyme. As a result, it is thought that our results will contribute to the search for new therapeutic agent studies using epigenetic approaches against AD.

Patent Blue V (PBV) is a water-soluble synthetic dyestuff that is used as a coloring agent in the food industry and for medical imaging in health monitoring. The aim of this study was to investigate the in vitro clastogenic, aneugenic and cytotoxic effects of PBV in human peripheral lymphocytes using micronucleus assay, comet assay, as well as plasmid DNA interaction and bacterial AMES tests. In addition to

PubMedID: 30421368 Metal-oxide nanoparticles (NPs), as a new emerging technological compound, promise a wide range of usage areas and consequently have the potential to cause environmental toxicology. In the present work, aluminum (Al 2 O 3 ), copper (CuO), and titanium (TiO 2 ) nanoparticles (NPs) were administered via oral gavage to mature female rats (Rattus norvegicus var. albinos) for 14 days with a dose series of 0 (control), 0.5, 5, and 50 (mg/kg b.w./day). Enzyme activities of the antioxidant system such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), and glutathione reductase (GR) in the liver were measured. Transmission electron microscope (TEM) images of the liver were taken to demonstrate NP accumulation and distribution in liver tissue. Data showed that all NPs caused some significant (P > 0.05) alterations in the activities of antioxidant enzymes. CAT activity increased after CuO and TiO 2 administrations, while SOD activity decreased after Al 2 O 3 administration. The activities of enzymes associated with glutathione (GR, GPx, GST) metabolisms were also significantly altered by NPs. GPx activity increased in rats received Al 2 O 3 , CuO NPs, while GR activity increased only by Al 2 O 3 . However, there were increases (TiO 2 ) and decreases (CuO) in GST activity in the liver of rats. TEM images of the liver demonstrated that all NPs accumulated in the liver, even at the lowest dose. This study indicated that the antioxidant enzymes in the liver of rats were affected by all NPs, suggesting the antioxidant system of rats suffered after NP administration. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Acknowledgements This study was produced from PhD Thesis of Dr. E.G. Canli, except nanoparticle characterizations and supported by the research fund (FDK-2017-8197) of Cukurova University (Turkey). We thank Dr. G. Atli for her help.

Life is a short process between mortality and immortality. In fact, immortality is not as interesting as imagined. Together with the transition from unicellular cells to multicellular organisms, cytotoxicity has a different meaning. While cytotoxicity in a single-celled organism refers to death, it acts as one of the driving forces of differentiation outside of death in the multicellular organism. To understand cytotoxicity it is necessary to understand cell cycle stages and control of these stages. In the cell cycle process, the progression of one of the progressive stages to the next phase is very important in terms of cell health and integrity. Causes that hinder the progression of this process may sometimes induce cytostatic or cytotoxic outcome. However, there is a thin line between cytotoxicity and immortality, which is the contrast of each other. Occasionally, if the cytotoxicity that has to take place does not occur, immortality may occur. To what extent which cell is affected by which cytotoxic agent is one of the most important issues that science should focus on. It must be known that drugs are poisons that dose and duration are optimized.

Cell division is a phenomenon that is encountered in all cells in nature. While normal cell division results in proliferation in single-celled organisms, and development and repair in multicellular organisms, aberrant and untimely cell division results in tumor formation. Therefore, the understanding of the cell division is hidden in identifying the details of the molecular mechanisms that govern cellular division at the exact time and under right conditions. Sometimes these molecular mechanisms are distorted by both intrinsic and extracellular factors, and the division process halts or deviates to an abnormal pathway. At this point, it is essential that the abnormal cells are removed from the tissue by an appropriate mechanism. In this context, in this review, general and specific information about cell division and its molecular control mechanisms were discussed, and different types of cell death mechanisms were mentioned accordingly. In addition, chemical, biological, and physical cytotoxic agents that negatively affect cell division and their mechanisms of action are explained. Finally, a brief review of the principles of different cytotoxicity (cell viability and proliferation) test systems has been performed to provide a source of information for investigators who study cell viability, proliferation, or different types of cellular death pathways.

PubMedID: 30965278 Nanoparticle (NP) forms of aluminium oxide (Al 2 O 3 ) are used in various fields such as engineering, pharmacy, medicine etc. Compounds containing aluminium oxide NPs may present toxic effects after certain thresholds. Thus, the present study was carried out to determine the effects of Al 2 O 3 nanoparticles (Al-NPs) in rats. For this aim, different doses (0, 0.5, 5, 50 mg/kg b.w./day) of Al NP (˜40 nm) were orally administered to female rats (Rattus norvegicus var. albinus) for 14 days and the response of several biomarkers such as activities of ATPases (total ATPase, Na,K-ATPase, Mg-ATPase) and acetylcholinesterase (AChE), levels of different glutathione forms and thiobarbituric acid reactive substances (TBARS) were measured in different tissues. Additionally, tissue accumulation of Al-NPs was demonstrated by a transmission electron microscope (TEM). The images showed the presence of Al-NP aggregates in all the tissues at all doses. The sizes of NP aggregates were dependent on NP doses and it was a bit more loose in the brain than in the liver and kidney. AChE activity in the brain decreased significantly at all NP doses, whereas TBARS levels in the liver did not alter significantly at any NP dose. Although there was no significant change in ATPase activities in the intestine at any NP dose, there were significant decreases in the kidney and brain. There were some variations in the levels of total glutathione (tGSH), oxidized glutathione (GSSG) and reduced glutathione (rGSH), though these variations were not significant (P > 0.05). Likewise, the ratio of rGSH/GSSG also did not differ significantly among NP doses and control. The brain seems most affected organ following Al-NP administration. This study demonstrated that most biomarkers in the tissues of rats were affected by Al-NP, showing the signal of toxic effects and suggests further studies to understand better the effects of Al NPs, especially in their use for pharmacology. © 2019 Elsevier B.V. This study was produced from PhD Thesis of E.G. Canli, except nanoparticle characterization and supported by the research fund ( FDK-2017-8197 ) of Cukurova University (Turkey). We thank physician Dr. C. Gumus for his valuable help about nanoparticles.

PubMedID: 25733130 Deferasirox (commercially formulated as Exjade®) is one of the effective iron chelators used in treatment of iron overload diseases. In this study the effect of this substance for chromosome aberration, sister chromatid exchange and mitotic index was studied by in vitro (by using human peripheral lymphocytes) and in vivo (by using rat) analysis. Deferasirox increased the sister chromatid exchange frequency in all tested concentrations and periods in vitro. Also, in the presence of metabolic activator, the substance led to a statistically significant increase in the sister chromatid exchange frequencies only at high concentration. While in in vitro analysis the substance significantly increased abnormal cell percentages in all concentrations, in in vivo study the substance increased chromosome aberrations only in two concentrations at 12. h treatment. In the cultured lymphocytes, deferasirox showed cytotoxicity by significantly reducing proliferation index and mitotic index values. While in the presence of metabolic activation it did not affect the proliferation index frequency, it had a stimulant effect on the mitotic index frequency. Deferasirox reduced significantly the mitotic index value in the bone marrow cells especially in high concentration and short treatment period (12. h). © 2015 Elsevier B.V. UGC-DAE Consortium for Scientific Research, University Grants Commission We wish to thank the Cukurova University Scientific Research Commission for supporting our study through project grants no. FEF2010D11 . We would like to thank Ebrahim Valipour for helping to edit our manuscript language carefully.

Sertraline (SRT) is an antidepressant agent used as a neuronal selective serotonin-reuptake inhibitor (SSRI). SRT blocks serotonin reuptake and increases serotonin stimulation of somatodendritic serotonin 1A receptor (5-HT1AR) and terminal autoreceptors in the brain. In the present study, the genotoxic potential of SRT was evaluated using cytokinesis-block micronucleus (CBMN) cytome assay in peripheral blood lymphocytes of healthy human subjects. DNA cleavage-protective effects of SRT were analyzed on plasmid pBR322. In addition, biochemical parameters of total oxidant status (TOS) and total antioxidant status (TAS) in blood plasma were measured to quantitate oxidative stress. Human peripheral blood lymphocytes were exposed to four different concentrations (1.25, 2.5, 3.75 and 5 µg/mL) of SRT for 24-or 48-h treatment periods. In this study, SRT was not found to induce MN formation either in 24-or 48-h treatment periods. In contrast, SRT concentration-dependently decreased the percentage of MN and MNBN (r=-0.979, p

Delphinidin is an anthocyanidin which is found in fruits and vegetables as a primary plant pigment used for various purposes. The purpose of this study was to investigate the in vitro genotoxic and antigenotoxic effects of delphinidin chloride (DC) in human peripheral blood lymphocytes. Final concentrations of 25 µM, 50 µM, 75 µM and 100 µM of DC were tested for 24 or 48 hours treatment periods. For detection of possible antigenotoxic potential of DC, human peripheral lymphocytes were co-treated with DC and a known clastogenic agent mitomycin-C (MMC). Genotoxic and antigenotoxic effects of DC were determined with the chromosome aberration (CA) and micronucleus (MN) tests. Cytotoxic effect of DC was determined by measuring the nuclear division index (NDI) and mitotic index (MI). Additionally, total oxidant and antioxidant values were determined by a spectrophotometric method. CA variations resulting from DC treatments did not reveal statistical significance as compared with controls. In tubes treated with DC and MMC together, DC significantly decreased the CA frequency caused by MMC (P?0.01). This decrease was almost 50% as compared to the positive control MMC. In this study, DC alone did not lead to the CA and MN formation in all culture tubes. DC did not cause a significant oxidative stress. DC has an antigenotoxic effect against the mutagenic effects of MMC. © 2018 Marmara University Press. UGC-DAE Consortium for Scientific Research, University Grants Commission: FLY-2014-2688 Acknowledgements: This study was supported by the Cukurova University Scientific Research Commission [grant numbers FLY-2014-2688].

Bu calisma antitiroid ilac Propycil®’in cesitli test bakterileri uzerindeki antibakteriyel aktivitesinin belirlenmesi ve potansiyel mutajenik etkisinin Ames / Salmonella / Mikrozom test sistemi ile saptanmasi amaciyla yapilmistir. Antibakteriyel aktivite testleri esnasinda test bakterisi olarak Staphylococcus aureus ATCC 6538, Pseudomonas aeruginosa ATCC 9027, Bacillus megaterium DSM 32 ve klinik izolat olan Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae kullanilmistir. Mutajen etki calismalarinda ise Ames Testi tercih edilmis olup, Salmonella typhimurium TA 98 ve TA 100 suslari kullanilmistir. Elde edilen bulgular neticesinde Propycil®’in test edilen bakterilerinden sadece Klebsiella pneumoniae’ye karsi 13,35 mm ve Pseudomonas aeruginosa ATCC 9027’ye karsi ise 15,46 mm inhibisyon zonu olusturdugu tespit edilmistir. Ames testi sonucunda denenen dozlarin hic biri TA 98 susu uzerinde cerceve kaymasi mutasyonuna neden olmazken, TA 100 susu uzerinde denenen en yuksek doz haric diger tum dozlar baz cifti degisimi mutasyonuna sebep oldugu belirlenmistir.

PubMedID: 25308555 This study was performed to investigate cytogenetic effects of NSAID flurbiprofen which was used as active ingredient in some analgesic, antipyretic and anti-inflammatory drugs. Genotoxic effect of flurbiprofen was investigated using in vivo chromosome aberration (CA) test and random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) test. Also, oxidative stress potential of flurbiprofen was determined by measuring total oxidant and antioxidant level which occurred with flurbiprofen treatment in rat peripheral blood. For these purposes, rats were treated with three concentrations of flurbiprofen (29.25, 58.50 and 117 mg/kg, body weight) in single dose at two different treatment periods (12 and 24 h). According to the results, flurbiprofen did not affect chromosome aberrations in rat bone marrow cells with CA test. In RAPD-PCR test, polymorphic bands were unaffected. Also, test substance did not change total oxidant and antioxidant status (except for 58.50 and 117 mg/kg, 12 h) and therefore it did not lead to significant increase on oxidative stress (again except 58.50 and 117 mg/kg, 12 h). However, flurbiprofen reduced to mitotic indexes and these reductions were dose-dependent for 12 h treatment. In summary, flurbiprofen did not show significant genotoxic effect. But it caused cytotoxicity in rat bone marrow cells. © 2014 Informa Healthcare USA, Inc. FEF2013YL25 The authors report no financial conflicts of interest. The authors alone are responsible for the content and writing of this paper. This study was funded by Cukurova University Research Fund: FEF2013YL25.

PubMedID: 27600436 Flurbiprofen (FLB) (anti-inflammatory and analgesic drug) and roxithromycin (RXM) (antibiotic) were widely used in world wide. This study deals with investigation of genotoxicity, cytotoxicity, and oxidative stress effects of a particular combination of these drugs in human cultured lymphocytes. Also, DNA damaging-protective effects of combination of these drugs were analyzed on plasmid DNA. Human lymphocytes were treated with different concentrations (FLB + RXM; 10 µg/mL + 25 µg/mL, 15 µg/mL + 50 µg/mL, and 20 µg/mL + 100 µg/mL) of the drugs following by study of their genotoxic and cytotoxic effects by analysis of cytokinesis-block micronucleus test and nuclear division index, respectively. The effect of the combination in aspect of anti-oxidative and DNA damaging activity was evaluated on Pet-22b plasmid. According to our results, the combination of FLB and RXM did not show a notable genotoxic effect on cells. Although each of the substances had been shown as a cytotoxic agent by previous researchers, in this research, the combination of these drugs did not exhibit any adverse effect on cell division. FLB had DNA protection effect against H2O2 while in combination with RXM had not the same effect on the plasmid. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

Eucalyptus also is known as cineol, is a colorless organic compound belongs to the terpene group. It is the main compound of essential oils of Eucalyptus globulus plant. It is used as a wide range of processed food and some medicines due to certain preferred properties. In vitro genotoxic and cytotoxic effect of eucalyptol was investigated by using cultured human peripheral blood lymphocytes. The various concentrations of eucalyptol (at very low doses) were tested some treatment periods. Eucalyptol did not affect sister-chromatid exchange frequency at any concentrations and treatment periods. Eucalyptol slightly increased chromosome aberration but this increase was not statistically significant. Alike, the test substance did not induce formation of micronuclei. Eucalyptol reduced the replication index significantly at the highest concentration when compared with control and solvent control. Higher concentrations (210 and 280nL/mL) of eucalyptol reduced the mitotic index (MI) significantly. The same concentrations of eucalyptol reduced the nuclear division index. NDI decreased at all concentrations (except the lowest). Eucalyptol did not affect total oxidant or total antioxidant values at all concentrations. As a result, there was not any significantchangesinoxidativestressindex. Eucalyptol showed cytotoxic effect in general but this effect is not caused by oxidative stress.

PubMedID: 27998191 Macrolide antibiotic roxithromycin was evaluated in terms of its genotoxic, cytotoxic and oxidative stress effects. For this purpose; 25, 50, 100 and 200 µg/mL concentrations of roxithromycin were dissolved in dimethyl sulfoxide and treated to human peripheral blood lymphocytes for two different treatment periods (24 and 48 h). In chromosome aberration (CA) and micronucleus (MN) tests, roxithromycin did not show genotoxic effect. But it induced sister chromatid exchange (SCE) at the highest concentration (200 µg/mL) for the 24-h treatment period and at all concentrations (except 25 µg/mL) for the 48-h treatment period. Looking at cytotoxic effect of roxithromycin, statistically insignificant decreases on mitotic index and proliferation index were observed. Roxithromycin decreased nuclear division index (NDI) at highest two concentrations (100 and 200 µg/mL) for the 24-h treatment period and at all concentrations (expect 25 µg/mL) for the 48-h treatment period. Total oxidant values, total antioxidant values and oxidative stress index did not change with roxithromycin treatment. Eventually, roxithromycin did not have genotoxic and oxidative stress effects in human-cultured lymphocytes. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

PubMedID: 18692594 Cyfluthrin (CAS no. 68359-37-5), a synthetic fluorinated pyrethroid insecticide, is widely used in the home environment and in agriculture because of its high activity against a broad spectrum of insect pests and its low animal toxicity. There are no adequate data on genotoxic effects of cyfluthrin. The aim of this study was to analyze the potential genotoxic effects of cyfluthrin. The genotoxicity of cyfluthrin was evaluated, in vitro, by assessing the ability of the insecticide to induce gene mutation (evaluated using the Ames/microsome test), chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronucleus (MN) formation in cultured human peripheral blood lymphocytes. Additionally, CAs and cytotoxicity induced by cyfluthrin were investigated in rat (Rattus norvegicus var. Albinos) bone-marrow cells to assess in vivo genotoxicity of cyfluthrin. The counts of reverse mutations in Salmonella typhimurium were not significantly increased (P > 0.05). The frequency of CAs in human lymphocytes, treated with any concentration of cyfluthrin (500, 1000 or 2000 µg/ml) for a 24-h period, was not significantly increased (P > 0.05). In contrast, CA was significantly increased for the highest two concentrations (1000 and 2000 µg/ml) in the 48-h treatment group compared with the control group (dimethyl sulfoxide, DMSO). Micronucleus formation was significantly (P < 0.05) increased for all doses after the 48-h treatment, although the frequency of SCE did not increase significantly (P > 0.05). Mitotic index (MI), proliferation index (PI) and nuclear division index (NDI) decreased significantly (P < 0.05) due to the potential cytotoxicity of cyfluthrin, especially after the 48-h treatment period. The frequency of chromosome aberrations in bone-marrow cells of rats treated with the test substance increased significantly (P < 0.05) for all doses (250, 500 and 1000 mg/kg body weight) for the two treatment periods (12 and 24 h) and the two administration routes, viz. intraperitoneal injection (i.p.) and oral gavage (gvg). In vivo cytotoxicity of cyfluthrin was detected only after administration by gavage for the 24-h treatment period. All these findings were not dose-dependent. © 2008 Elsevier B.V. All rights reserved.

PubMedID: 18338376 Potassium metabisulfite (PMB) is used as an antimicrobial substance in many kinds of foods. In the present study, the effects of PMB on chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and micronucleus (MN) formation in human lymphocytes and as well as its effect on CAs in bone marraw cells of rats were investigated. The human lymphocytes were treated with 25, 50, 100, and 200 ng/ml of PMB for 24 and 48 hr. PMB was also intraperitoneally (ip) injected to the rats as a single dose of 150, 300, and 600 mg/kg body weight (b.w.) for 12 and 24 hr before sacrifice. PMB induced abnormalities such as structural and numerical (total) CAs, SCEs, and MN formations in a dose dependent manner in the lymphocytes of the 24-and 48-hr treatment periods. In addition, PMB showed a cytotoxic effect by decreasing the replication index (RI), mitotic index (MI) and nuclear division index (NDI) in a dose dependent manner in human lymphocytes. The compound induced CA as well and decreased the MI in bone marrow cells of rats. It might be concluded that PMB had a high genotoxic and cytotoxic risk. © 2008 Wiley-Liss, Inc.

PubMedID: 26738809 Flurbiprofen is non-steroidal anti-inflammatory drug which is commonly used for its analgesic, antipyretic, and anti-inflammatory effects. The purpose of the study was to explore the genotoxic and cytotoxic effects of flurbiprofen in human cultured lymphocytes by sister chromatid exchange, chromosome aberration, and cytokinesis-blocked micronucleus tests. 10, 20, 30, and 40 g/mL concentrations of flurbiprofen (solvent is DMSO) were used to treatment of human cultured lymphocytes at two different treatment periods (24 and 48 h). Flurbiprofen had no significant genotoxic effect in any of these tests. But exposing to flurbiprofen for 24 and 48 h led to significant decrease on proliferation index, mitotic index, and nuclear division index (NDI). Also, all decreases were concentration-dependent (except NDI at 24 h treatment period). Consequently, the findings of this research showed that flurbiprofen had cytotoxic effects in human blood lymphocytes. © 2016 Taylor & Francis.

The aim of this study was to investigate the mutagenic and antimutagenic effects of Ecballium elaterium (EE) fruit juice, which has an anti-inflammatory effect, using in vitro human peripheral lymphocytes. To investigate the mutagenic effects of the EE fruit juice, human peripheral lymphocytes were treated with three doses (18, 36, and 72 µl/l) of fruit juice alone for 24 and 48 h. For investigating the antimutagenic effects of the EE fruit juice, the human lymphocytes were also treated with the mixture of the fruit juice and 0.25 µg/ml MMC. The EE fruit juice induced the percentage of total CA when used alone (especially the percentage of structural CA than the percentage of the numerical CA) and synergically induced the percentage of total CA when used as a mixture with MMC. The EE fruit juice did not affect the SCE frequency for 24 and 48 h treatment time. In contrast, EE and MMC as a mixture sinergically induced the SCE frequency at the highest concentration for 48 h treatment time only. EE alone did not decrease the RI while it decreased the MI in a dose-dependent manner. EE and MMC as a mixture have a higher cytotoxic effect than the cytotoxic effects of EE alone. As a result, it can be concluded that EE had no antimutagenic effect while EE had a mutagenic and a cytotoxic effect in human peripheral lymphocytes. © Pleiades Publishing, Inc., 2006. ACKNOWLEDGMENTS This study was supported by the C.U. Research Fund, project no. FEF2002BAP17.

WOS: 000223950300005, PubMed ID: 15478947, In the present study, the genotoxic effects of the low-calorie sweetener aspartame (ASP), which is a dipeptide derivative, was investigated using chromosome aberration (CA) test, sister chromatid exchange (SCE) test, micronucleus test in human lymphocytes and also Ames/Salmonella/ microsome test. ASP induced CAs at all concentrations (500, 1000 and 2000 mug/ml) and treatment periods (24 and 48 h) dose-dependently, while it did not induce SCEs. On. the other hand, ASP decreased the replication index (RI) only at the highest concentration for 48 h treatment period. However, ASP decreased the mitotic index (MI) at all concentrations and treatment periods dose-dependently. In addition, ASP induced micronuclei at the highest concentrations only. This induction was also dose-dependent for 48 hours treatment period. ASP was not mutagenic for Salmonella typhimurium TA98 and TA 100 strains in the absence and presence of S9 mix.

This study was performed to determine the cytogenetic effects of short-term thermal stress in human cultured lymphocytes. Experimental heat shock (39 °C) was performed alone or with the addition of mitomycin C (MMC) to determine the synergistic or antagonistic effects of heat shock on genotoxicity induced by MMC. In this study, during culture periods of 72 h, human peripheral blood lymphocytes were exposed to heat shock for specified durations (30, 60, 120, and 240 min) 24 or 48 h before harvest. According to our results, the selected temperatures did not show genotoxic or mutagenic effects. In summary, the heat shock tested did not show any cytogenetic effect on the cultured blood cells and did not cause significant alterations in genotoxicity induced by MMC. This study was performed to determine the cytogenetic effects of short-term thermal stress in human cultured lymphocytes. Experimental heat shock (39 °C) was performed alone or with the addition of mitomycin C (MMC) to determine the synergistic or antagonistic effects of heat shock on genotoxicity induced by MMC. In this study, during culture periods of 72 h, human peripheral blood lymphocytes were exposed to heat shock for specified durations (30, 60, 120, and 240 min) 24 or 48 h before harvest. According to our results, the selected temperatures did not show genotoxic or mutagenic effects. In summary, the heat shock tested did not show any cytogenetic effect on the cultured blood cells and did not cause significant alterations in genotoxicity induced by MMC.

Iron overload is a major health problem for patients who have to have continuous blood transfusions. It brings some metabolic problems together. Various iron chelating agents are being used for treatment of hemochromatosis which arises from excess iron accumulation. This study was conducted with the aim of determining whether deferasirox used as an iron chelator in patients with hemochromatosis has genotoxic effects. Commercial form of deferasirox, Exjade was used as test material. Test material showed a general mutagen character in mutant strains of Salmonella typhimurium. Deferasirox has also led to an increase in mutagenity-related polymorphic band count in random amplification of polymorphic DNA test done with bone marrow cells of rats. Similarly, test material has increased micronucleus formation in cultured in vitro human peripheral lymphocytes particularly in 48 h period. Consistently with the abovementioned findings, deferasirox reduced nuclear division index (NDI) compared to controls and some part of these reductions are statistically significant. NDI reductions were found at positive control levels at high concentrations. © 2013 Springer Science+Business Media. 111T017 Acknowledgments This work was supported by the Basic Science Research and Support Group at the TUBITAK (Project no: 111T017).

This study was conducted with the aim of determining the effects of periodical hormonal fluctuations related to the menstrual cycle on chromosome sensitivity and cytotoxicity. The study group consisted of 8 healthy donors (4 nonsmokers and 4 smokers). Cytogenetic tests were done in vitro (in test tubes), and the known mutagenic effect of mitomycin C was added to determine chromosome sensitivity. Blood was drawn from the donors at specified time intervals (follicular phase, ovulation phase, and luteal phase), and control groups and mitomycin C-treated groups were formed. In the controls, the highest sister chromatid exchange frequency was detected in the follicular phase and the lowest frequency was detected in the luteal phase of nonsmokers. In smokers, the highest sister chromatid exchange frequency was detected in the ovulation phase and the lowest frequency was detected in the luteal phase. In terms of chromosomal aberrations, the highest values were detected in the follicular phase and the lowest values were detected in the luteal phase in nonsmokers. On the contrary, the highest rate of anomaly was detected in the luteal phase and the lowest rate of anomaly was detected in the follicular phase in smokers. However, there was no statistically significant difference between these findings. The data of the MMC application were similar in both groups. In this study, both the follicular phase and the ovulation phase showed slightly higher chromosome sensitivity, while the chromosomes in the luteal phase were the most stable. These results are probably due to hormonal fluctuation. This study was conducted with the aim of determining the effects of periodical hormonal fluctuations related to the menstrual cycle on chromosome sensitivity and cytotoxicity. The study group consisted of 8 healthy donors (4 nonsmokers and 4 smokers). Cytogenetic tests were done in vitro (in test tubes), and the known mutagenic effect of mitomycin C was added to determine chromosome sensitivity. Blood was drawn from the donors at specified time intervals (follicular phase, ovulation phase, and luteal phase), and control groups and mitomycin C-treated groups were formed. In the controls, the highest sister chromatid exchange frequency was detected in the follicular phase and the lowest frequency was detected in the luteal phase of nonsmokers. In smokers, the highest sister chromatid exchange frequency was detected in the ovulation phase and the lowest frequency was detected in the luteal phase. In terms of chromosomal aberrations, the highest values were detected in the follicular phase and the lowest values were detected in the luteal phase in nonsmokers. On the contrary, the highest rate of anomaly was detected in the luteal phase and the lowest rate of anomaly was detected in the follicular phase in smokers. However, there was no statistically significant difference between these findings. The data of the MMC application were similar in both groups. In this study, both the follicular phase and the ovulation phase showed slightly higher chromosome sensitivity, while the chromosomes in the luteal phase were the most stable. These results are probably due to hormonal fluctuation.

The aim of this study was to evaluate the genotoxic effect of a bovine bone-derived hydroxyapatite (HA), Boneplus-xs (B-P-XS). The genotoxicity of B-P-XS was investigated by examining the potential of the xenograft (B-P-XS) to induce gene mutation (evaluated using the Ames test), in vitro chromosome aberration (CA), and sister chromatid exchange (SCE) with tests in cultured human peripheral lymphocytes. Counts of reverse mutations in Salmonella typhimurium TA98 and TA100 strains were not found to be signifi cantly increased after treatment with B-PXS (P > 0.05). The presence of B-P-XS in peripheral blood culture for 24 and 48 h did not lead to a significant increase in the frequency of CAs (P > 0.05) and SCEs (P > 0.05) when compared to the solvent control (dimethyl sulfoxide). When compared with the control group (untreated), B-P-XS significantly decreased the mitotic index; however, the decrement was not statistically significant when compared with the solvent control in any of the concentrations and treatment times (P > 0.05). In addition, no significant changes in the proliferation index were observed after treatment with B-P-XS when compared to both the control and the solvent control. As a result of this study, we suggest that HA microparticles greater than 200 µm do not constitute a genotoxic risk for patients undergoing dental surgery. The aim of this study was to evaluate the genotoxic effect of a bovine bone-derived hydroxyapatite (HA), Boneplus-xs (B-P-XS). The genotoxicity of B-P-XS was investigated by examining the potential of the xenograft (B-P-XS) to induce gene mutation (evaluated using the Ames test), in vitro chromosome aberration (CA), and sister chromatid exchange (SCE) with tests in cultured human peripheral lymphocytes. Counts of reverse mutations in Salmonella typhimurium TA98 and TA100 strains were not found to be signifi cantly increased after treatment with B-PXS (P > 0.05). The presence of B-P-XS in peripheral blood culture for 24 and 48 h did not lead to a significant increase in the frequency of CAs (P > 0.05) and SCEs (P > 0.05) when compared to the solvent control (dimethyl sulfoxide). When compared with the control group (untreated), B-P-XS significantly decreased the mitotic index; however, the decrement was not statistically significant when compared with the solvent control in any of the concentrations and treatment times (P > 0.05). In addition, no significant changes in the proliferation index were observed after treatment with B-P-XS when compared to both the control and the solvent control. As a result of this study, we suggest that HA microparticles greater than 200 µm do not constitute a genotoxic risk for patients undergoing dental surgery.

The aim of this study was to investigate the genotoxic and/or cytotoxic effects of Tamiflu, commercial form of the oseltamivir antiviral and most frequently prescribed for the treatment of influenza infections, on cultured human peripheral lymphocytes by using sister chromatid exchange (SCE), chromosomal aberration (CA), and cytokinesis-blocked micronucleus (CBMN) assays. Cells were treated with 0.5, 1, 2 µg/mL oseltamivir, the Tamiflu capsule ingredient, for 24 or 48 h in the absence or presence of an exogenous metabolic activation system (S9 mix). The test chemical did not demonstrate any genotoxic effect dose-dependently but it showed a weak cytotoxicity on cells in this study. On the other hand, some concentrations of Tamiflu (2 µg/mL without S9 mix for 48 h and 1 µg/mL with S9 mix) induced SCE and also decreased significantly the proliferation index (PI) (48 h period) and the nuclear division index (NDI) (24 h period) (P < 0.05) in the absence of S9 mix. Considering the results, Tamiflu did not induce significant increases of CA or micronucleated cells in vitro in cultured peripheral blood lymphocytes under the treatment conditions used but weak SCE induction was observed. On the other hand, the weak cytotoxic effects observed disappeared in the cultures treated in presence of the S9 mix. © Springer Science+Business Media B.V. 2011. Fundamental Research Fund of Shandong University: FEF2008YL3 Acknowledgments This study was funded by University Research Fund; FEF2008YL3.

PubMedID: 18330787 The aim of this study was to determine the possible genotoxic effects of biphenyl (E230), which is used as an antimicrobial agent in food by using sister chromatid exchanges (SCEs), chromosome aberrations (CAs), and micronucleus (MN) tests in human peripheral lymphocytes. The human peripheral lymphocytes were treated with four concentrations of biphenyl (10, 30, 50, and 70 µg/mL) for 24- and 48-h treatment periods. In the present study, biphenyl significantly increased the frequency of SCEs, CAs, and the frequency of MN when compared with both untreated control and solvent (dimethyl sulfoxide) control. The inductions of these abnormalities were in a dose-dependent manner. Biphenyl was capable to induce the structural CAs instead of numerical CAs. Biphenyl also showed a cytotoxic effect by decreasing the replication index at the highest two concentrations for 48 h and nuclear division index at the highest two concentrations for the 24- and 48-h treatment periods. However, biphenyl did not affect the mitotic index (MI). Copyright © Informa Healthcare USA, Inc. Fundamental Research Fund of Shandong University Çukurova Üniversitesi The Çukurova University Research Fund funded this study (grant no. FEF2006YL22).

WOS: 000179021800003 PubMed ID: 12395403 The aim of this study was to investigate, by using chromosome aberration (CA) and sister chromatid exchange (SCE) tests, whether or not the workers employed in the iskenderun (Turkey) iron and steel factory have any genotoxic risk. The CA and the SCE were investigated in 48 males employed in a coke ovens unit and 8 males employed in a product side unit of the factory and in control groups. The frequency of CA was higher while the frequency of the SCE was not in all the smoker-nonsmoker workers than in smoker-nonsmoker control groups. In addition, there was no significant decrease in the RI, while the MI was significantly lower than in the controls. (C) 2002 Wiley-Liss, Inc.

PubMedID: 11342236 The aim of this study was to investigate the ability of sodium metabisulfite (SMB) which is used as an antimicrobial substance in food, to induce chromosome aberrations (CA) and sister chromatid exchanges (SCE) in human lymphocytes. SMB-induced CAs and SCEs at all concentrations (75, 150 and 300 µg/ml) and treatment periods (24 and 48 h) dose-dependently. However, SMB decreased the replication index (RI) and the mitotic index (MI) at the concentrations of 150 and 300 µg/ml for 24 and 48 h treatment periods. This decrease was dose-dependent as well. © 2001 Elsevier Science B.V.

The aim of this study was to investigate potential clastogenicity/genotoxicity of the antibiotic spiramycin in bone marrow cells of rats (Rattus norvegicus var. albinos). In the study, spiramycin induced the chromosome aberations at all concentrations (100, 200, 400 mg/kg bwt. (body weight) /d oral) in 21 d when compared with the solvent control group (sunflower seed oil). In addition, spiramycin induced the chromosomal aberration (CA) at only 200 mg/kg bwt. intraperitoneal (i.p.) in 12 h and 100 and 400 mg/kg bwt. i.p. in 24 h when compared with the control group. Spiramycin induced the micronucleated polichromatic erythrocytes (MNPCE) only at 200 mg/kg bwt. i.p. in 12 h and 100 mg/kg bwt. i.p. in 24 h. However, there was no significant difference in the formation of micronuclei at the other concentrations.

The aim of this study was to investigate the genotoxic effects of spiramycin which is an effective ingredient of the antibiotic rovamycine in bone marrow cells of rats (Rattus norvegicus var. albinos). The rats were treated with 100, 200, 400 mg/kg bwt/day of spiramycin. Animals were treated with the above concentrations for 7 days and the bone marrow preparations were prepared after 6 and 12 h from the last administration. In 100 mg/kg bwt/day, spiramycin increased the percentages of the abnormal cells and the chromosomal aberration per cell (CA/cell) in the bone marrow cells of rats that were sacrificed after 6 h from the last administration. It could not induce the abnormalities however at the other concentrations (200 and 400 mg/kg bwt/day). The mitotic index (MI) was not decreased by any treatment of spiramycin. Spiramycin did not increase neither the percentage of abnormal cells nor the CA/cell in bone marrow cells of rats which sacrificed after 12 h from the last administration, whereas it generally decreased the MI in this treatment. Spiramycin did not affect the formation of chromosomal gaps.

Etoxazole is a member of the diphenyl oxazoline class of insecticide, which was newly developed for use on pome fruits, cotton and strawberries as an acaricide. In the present study, genotoxic effects of acaricide etoxazole (ETX) (miticide/ovicide) were investigated using chromosome aberration (CA) test, sister chromatid exchange (SCE) test, and micronucleus test in human lymphocytes. ETX induced the CAs at all concentrations (5, 10, and 20 µg/ml) for 24 h and also induced the CA at the highest concentration (20 µg/ml) for 48 h only. The inducing the CAs for 48 h treatment period was dose-dependent. In addition, it induced the SCE at all concentrations and treatment periods in a dose-dependent manner as well. Although ETX decreased the mitotic index (MI) at all concentrations and treatment periods dose-dependently, it did not decrease the replication index (RI) when compared to the negative and solvent controls. In addition, ETX induced the micronucleus at all concentrations except 5 µg/ml for 48 h. This inducing was dose-dependent as well. It can be concluded that ETX has a potential genotoxic effects in cultured human peripheral lymphocytes. Copyright © 2004 by Rencüzogullari, Basri Ila, Kayraldiz, Arslan, Diler, and Topaktaş.