Genotoxic effects of chlorophenoxy herbicide diclofop-methyl in mice in vivo and in human lymphocytes in vitro

Diclofop-methyl (DM) is a chlorophenoxy derivative used in large quantities for the control of annual grasses in grain and vegetable crops. In this study, the genotoxic effects of DM were investigated by measuring chromosomal aberrations (CAs) in mouse bone-marrow cells and CA and the comet assay in human peripheral lymphocytes. Mice were treated with 15.63, 31.25, 62.5, and 125?mg/kg body weight of DM intraperitoneally for 24 hours, and 15.63-, 31.25-, 62.5-, 125-, and 250-μg/mL concentrations were applied to human lymphocytes for both 24 and 48 hours. In in vivo treatments, DM significantly, but not dose dependently, increased the total chromosome aberrations, compared to both negative and solvent controls. Cell proliferation was significantly, but not dose dependently, affected by all doses. In in vitro treatments, DM (except 15.63 μg/mL) significantly and dose dependently increased the frequency of chromosome aberrations. Also, 250 μg/mL of 48-hour treatment was found to be toxic. Cell proliferation was significantly and dose dependently affected by DM applications, when compared to negative control. In in vitro treatments, DM significantly decreased the mitotic index only at the highest concentration for 24 hours, and 62.5- and 125-μg/mL concentrations for 48 hours. In the comet assay, a significant and dose-dependent increase in comet-tail intensity was observed at 62.5-, 125-, and 250-μg/mL concentrations. The mean comet-tail length was significantly increased in all concentrations. Our results demonstrate that DM is genotoxic in mammalian cells in vivo and in vitro.     

Genotoxic evaluation of terbinafine in human lymphocytes in vitro

Terbinafine is an antimycotic drug usually used against several superficial fungal infections and with a potential application in the treatment of human cancers. Since to date there are few data on the genotoxic effects of terbinafine in mammalian cells, current study evaluated the potential genotoxic of such antifungal agent in cultured human peripheral blood lymphocytes. Terbinafine was used at the peak plasma concentration (1.0?μg/ml) and in four additional concentrations higher than the human plasmatic peak (5.0?μg/ml, 25.0?μg/ml, 50.0?μg/ml and 100.0?μg/ml). Chromosomal aberrations (CA), sister chromatid exchanges (SCE), micronuclei (MN), nucleoplasmic bridges (NP) and nuclear buds (NB) were scored as genetic endpoints. In all analysis no significant differences (α?=?0.05, Kruskal-Wallis test) were observed. Complementary criterion adopted to obtain the final response in cytogenetic agreed with statistical results. Therefore, results of this study showed that terbinafine neither induced CA, SCE, MN, NP and NB nor affected significantly mitotic, replication and cytokinesis-block proliferation indices in any of the tested concentrations. It may be assumed that terbinafine was not genotoxic or cytotoxic to cultured human peripheral blood lymphocytes in our experimental conditions.     

Genotoxic effects of chlorpyrifos,cypermethrin, endosulfan and 2,4‐D on human peripheral lymphocytes cultured from smokers and nonsmokers

Pesticides often cause environmental pollution and adverse effects on human health. We have chosen four structurally different pesticides (endosulfan, an organochlorine pesticide; chlorpyrifos, an organophosphate insecticide; cypermethrin, type II pyrethroid insecticide, and 2,4‐dichlorophenoxyacetic acid, a chlorinated aromatic hydrocarbon acid pesticide) to examine and compare their effects on DNA damage in acutely cultured human lymphocytes by the comet assay. In addition, possible differences in response between smoking and nonsmoking subjects were also investigated. Venous blood samples were obtained from healthy male nonsmoker (n = 7) and smoker (n = 8) donors. Primary cultures of lymphocytes were prepared and test groups were treated with three different concentrations (1, 5, and 10 μM) of endosulfan, chlorpyrifos, cypermehrin, and 2,4‐D. DNA damage was assessed by alkaline comet assay. We determined an increase in the ratio of DNA migration in human lymphocyte cell cultures as a result of treatment with cypermethrin, 2,4‐D and chlorpyrifos at high concentration. Endosulfan had no significant genotoxic effect even at 10 μM concentration. We suggest that chlorpyrifos and cypermethrin are more potentially genotoxic than endosulfan and 2,4‐D. Our findings also indicate that the only significant DNA damage between smokers and nonsmokers was observed in the 2,4‐D‐treated group. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2010.     

Genotoxic effects of 4-methylimidazole on human peripheral lymphocytes in vitro

4-Methylimidazole (4-MEI), a heterocyclic organic chemical compound, is widely found in many foods and consumed by people worldwide. In this research, we aimed to investigate the cytotoxic and genotoxic effects of 4-MEI on human lymphocytes. For this purpose, human peripheral blood lymphocytes were treated with four concentrations of 4-MEI (300, 450, 600 and 750?μg/ml) for 24?h and 48?h periods and in vitro sister chromatid exchange (SCE), chromosome aberration (CA) and micronucleus (MN) tests were used. 4-MEI induced SCE in human peripheral lymphocytes at three highest concentrations (450, 600 and 750?μg/ml) in 48?h treatment period. CA and MN were induced in human peripheral lymphocytes at two highest concentrations of 4-MEI (600 and 750?μg/ml) in 24?h and 48?h treatment periods. The highest concentration of 4-MEI (750?μg/ml) induced MN formation more than the positive control MMC in 24?h treatment period. In addition, 4-MEI led to a decrease in MI at the highest concentration (750?μg/ml) in 24?h treatment period and at all concentrations in 48?h treatment period. 4-MEI reduced PI at all concentrations in 24?h treatment period and at all concentrations (expect the lowest) for 48?h treatment period. 4-MEI reduced nuclear division index (NDI) at 24 and 48?h treatment periods, even at the highest two concentrations, decreased more than the positive control MMC. Our results showed that 4-MEI pose a genotoxic and cytotoxic effects for human peripheral lymphocytes.     

In vitro assessment of cytotoxic,genotoxic and mutagenic effects of antimalarial drugs artemisinin and artemether in human lymphocytes

Artemisinin is a substance extracted from the Chinese plant Artemisia annua L. widely used in natural medicine for the treatment of various diseases. Artemether is a substance synthesized from artemisinin, and both drugs are commonly administered in the treatment of malaria. Although considered effective antimalarial drugs, very little is known about the genotoxic, cytotoxic and mutagenic effects of these drugs. Therefore, in the present study, we evaluated the genotoxic, mutagenic and cytotoxic effects of artemisinin (12.5, 25 and 50?µg/mL) and artemether (7.46; 14.92 and 29.84?µg/mL) in cultured human lymphocytes using the comet assay, the micronucleus test and the cytotoxicity assay for detection of necrosis and apoptosis by acridine orange/ethidium bromide staining. Our results showed a significant increase (p?<?0.05) in the rate of DNA damage measured by comet assay and in the micronucleus frequency after treatment with both drugs. It was also observed that only artemisinin induced a statistically significant increase (p?<?0.05) in the number of lymphocytes with death by necrosis 48?h after treatment. The results demonstrated that these two drugs induce mutagenic, genotoxic and cytotoxic effects in cultured human lymphocytes. Our data indicate the need for caution in the use of such drugs, since genotoxic/mutagenic effects may increase the risk of carcinogenesis.     

Evaluation of salidroside in vitro and in vivo genotoxicity

It is reported that salidroside, the main component of a traditional Chinese medicine, Rhodiola rosea, has the efficacy of protecting Coxsackie virus impairment. As part of a safety evaluation on salidroside for use in the treatment of viral myocarditis, the present study evaluated potential genotoxicity of salidroside by using the standard battery of tests (i.e., bacterial reverse mutation assay, chromosomal aberrations assay, and mouse micronucleus assay) recommended by the State Food and Drug Administration of China. The results showed that salidroside was not genotoxic under the conditions of the reverse mutation assay, chromosomal aberrations assay, and mouse micronucleus assay conditions. The anticipated clinical dose seems to be smaller than the doses administered in the genotoxicity assays. With confirmation from further toxicity studies, salidroside would hopefully prove to be a safe anti-Coxsackie virus agent.     

Genotoxic effects of silver nanoparticles with/without coating in human liver HepG2 cells and in mice

With the rapid expansion of human exposure to silver nanoparticles (AgNPs), the genotoxicity screening is critical to the biosafety evaluation of nanosilver. This study assessed DNA damage and chromosomal aberration in the human hepatoma cell line (HepG2) as well as the effects on the micronucleus of bone marrow in mice induced by 20 nm polyvinylpyrrolidone‐coated nanosilver (PVP‐AgNPs) and 20 nm bare nanosilver (AgNPs). Our results showed that the two types of AgNPs, in doses of 20‐160 μg/mL, could cause genetic toxicological changes on HepG2 cells. The DNA damage degree of HepG2 cells in 20 nm AgNPs was higher than that in 20 nm PVP‐AgNPs, while the 20 nm PVP‐AgNPs caused more serious chromosomal aberration than 20 nm AgNPs. Both kinds of AgNPs caused genetic toxicity in a dose‐dependent manner in HepG2 cells. In the micronucleus test on mouse bone marrow cells, in doses of 10, 50 and 250 mg/kg body weight administered orally for 28 days once a day, the two kinds of AgNPs have no obvious inhibitory effect on the mouse bone marrow cells, and the effect of chromosome aberration could be documented at the high dose of 250 mg/kg. These results suggest that AgNPs have genotoxic effects in HepG2 cells and limited effects on bone marrow in mice; both in vitro and in vivo tests could be of great importance on the evaluation of genotoxicity of nanosilver. These findings can provide useful toxicological information that can help to assess genetic toxicity of nanosilver in vitro and in vivo.     

Evaluation of in vivo cytogenetic toxicity of europium hydroxide nanorods (EHNs) in male and female Swiss albino mice

Our group already demonstrated that europium hydroxide nanorods (EHNs) show none or mild toxicity in C57BL/6 mice even at high dose and exhibited excellent pro-angiogenic activity towards in vitro and in vivo models. In the present study, we evaluated the in vivo cytogenetic toxicity of intraperitoneally administered EHNs (12.5–250?mg/kg/b.w.) in male and female Swiss albino mice by analyzing chromosomal aberrations (CAs), mitotic index (MI), micronucleus (MN) from bone marrow and peripheral blood. Furthermore, we performed the cytogenetic toxicity study of EHNs towards Chinese hamster ovary (CHO) cells, in order to compare with the in vivo results. The results of CA assay of mice treated with EHNs (12.5–125?mg/kg/b.w.) showed no significant change in the formation of aberrant metaphases compared to the control group. Also, there was no significant difference in the number of dividing cells between the control group and EHNs-treated groups observed by MI study, suggesting the non-cytotoxicity of EHNs. Additionally, FACS study revealed that EHNs do not arrest cells at any phase of cell cycle in the mouse model. Furthermore, MN test of both bone marrow and peripheral blood showed no significant differences in the induction of MNs when compared with the control group. In vitro results from CHO cells also support our in vivo observations. Considering the role of angiogenesis by EHNs and the absence of its genotoxicity in mouse model, we strongly believe the future application of EHNs in treating various diseases, where angiogenesis plays an important role such as cardiovascular diseases, ischemic diseases and wound healing.     

Cytotoxic and genotoxic effects of paraquat in Hordeum vulgare and human lymphocytes in vitro

Two phylogenetically distant types of test‐systems—root tip meristems of barley (Hordeum vulgare) and human lymphocytes in vitro were used to detect genotoxicity and cytotoxicity induced by the herbicide paraquat (PQ) in the concentration range (10^?6 to 5 × 10^?4 mol/l). As an endpoint for cytotoxicity the mitotic index (MI) was evaluated. The frequency of chromosome aberrations (CA) and the frequency of micronuclei (MN) were used as endpoints for genotoxicity. A dose‐dependent increase of CA and MN was observed in both test systems, although the values for PQ‐induced MN were somewhat lower. The increase of the genotoxic effect corresponds to a decrease of mitotic activity. The structurally reconstructed barley karyotype MK14/2034 allowed the allocation of the PQ‐specific features of aberration distribution patterns and gave information about which chromosome segments in different chromosomal positions were involved in induced aberrations. Paraquat produced preferably isochromatid breaks and “aberration hot spots” in a restricted number of heterochromatin‐containing segments. The comparative analysis of susceptibility in the used test‐systems to PQ with respect to its cytotoxic and clastogenic effect showed that the human lymphocytes were more sensitive than Hordeum vulgare. © 2009 Wiley Periodicals, Inc. Environ Toxicol, 2010.     

Assessment of genotoxic effects of (4-methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone in human lymphocytes

(4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (PHT) belongs to the phenstatin family. This compound has been studied due to its potent cytotoxicity and ability to inhibit tubulin assembly. The present study aimed to evaluate the mutagenic potential of PHT in human lymphocytes. PHT displayed cytotoxicity in human lymphocytes with an IC₅₀ value of 5.68 μM, and therefore, concentrations of 0.25, 0.5, 1.0, 2.0, and 4.0 μM were used for all protocols. The alkaline comet assay and chromosome aberration (CA) analysis were performed in different phases of the cell cycle (G₁, G₁/S, transition, and G₂), to evaluate the DNA-damaging and clastogenic effects of PHT, respectively. CA analysis was carried out in the presence or absence of colchicine to evaluate the action of PHT in the mitotic phase. PHT was cytotoxic and significantly reduced the mitotic index with drug exposure in all phases of cell cycle. Interestingly, it induced an increase in mitotic index in experimental protocols without colchicine, corroborating its action as an antitubulin agent. It also induced DNA damage and was clastogenic with drug exposure in all phases of the cell cycle, in the presence or absence of colchicine. In conclusion, PHT induces DNA damage and exerts clastogenic effects in human lymphocytes.     

Genotoxic and cytotoxic effects of doxycycline in cultured human peripheral blood lymphocytes

Doxycycline (DOX) is a broad-spectrum tetracycline antibiotic used in the treatment of many infections. In this study, the genotoxic and cytotoxic effects of DOX in cultured human peripheral blood lymphocytes were investigated by measuring chromosome aberrations (CAs), cytokinesis-block micronucleus (CBMN) assay, mitotic index (MI), and nuclear division index (NDI). Cultures were treated with DOX at three concentrations (2, 4, and 6 µg/mL) for 48 hours. Mitomycin C (MMC) was used as a positive control. All the tested concentrations of DOX for MI and the higher concentrations (4 and 6 µg/mL) for NDI significantly decreased mitotic activity. However, there are no significant differences between negative control and all the tested concentrations of DOX for CA and MN frequencies. In conclusion, our results indicate that DOX has a cytotoxic effect, but not a genotoxic effect, on human peripheral blood lymphocyte cultures. Further detailed studies, especially about the cell-cycle kinetics of DOX, are required to elucidate the decreases in dividing cells and make a possible risk assessment on cells of patients receiving therapy with this drug. Further, if the specific cytostatic and cytotoxic potential of DOX to different types of cancer cells is investigated in detail, it may also have been used as an antitumoral drug.     

Induction of chromosomal aberrations by carbon nanotubes and titanium dioxide nanoparticles in human lymphocytes in vitro

Abstract

We examined if three commercially available nanomaterials – short singlewall carbon nanotubes (SWCNTs), short multiwall carbon nanotubes (MWCNTs) and nanosized titanium dioxide anatase (TiO₂; primary particle size <25 nm) – can induce structural chromosomal aberrations (CAs) in cultures of isolated human lymphocytes. To find a suitable sampling time, the cells were treated with 6.25–300 μg/ml of the nanomaterials for 24, 48 and 72 h. The 48-h treatment was the most effective, inducing a dose-dependent increase in chromosome-type CAs (all materials) and chromatid-type CAs (SWCNTs and TiO₂ anatase). The 72-h treatment yielded a positive result with SWCNTs. None of the treatments significantly affected cell count or the mitotic index. Our results suggest that with nanomaterials a continuous treatment for about two cell cycles is needed for CA induction, possibly reflecting access of nanomaterials to the nucleus during the first mitosis or delayed secondary genotoxic effect associated with the inflammatory process.     

Uranyl Nitrilotriacetate, a Stabilized Salt of Uranium, is Genotoxic in Nontransformed Human Colon Cells and in the Human Colon Adenoma Cell Line LT97

Previous uranium mining in the "Wismut" region in Germany enhancedenvironmental distribution of heavy metals and radionuclides.Carryover effects may now lead to contamination of locally producedfoods. Compounds of "Wismut" origin are probably genotoxic viatheir irradiating components (radon) or by interacting directlywith cellular macromolecules. To assess possible hazards, weinvestigated the genotoxic effects of uranyl nitrilotriacetate(U-NTA) in human colon tumor cells (HT29 clone 19A), adenomacells (LT97), and nontransformed primary colon cells. Theseare target cells of oral exposure to environmentally contaminatedfoods and represent different cellular stages during colorectalcarcinogenesis. Colon cells were incubated with U-NTA. Cellsurvival, cytotoxicity, cellular glutathione (GSH) levels, genotoxicity,and DNA repair capacity (comet assay), as well as gene- andchromosome-specific damage combination of comet assay and fluorescencein situ hybridization [FISH], 24-color FISH) were determined.U-NTA inhibited growth of HT29 clone 19A cells (75–2000µM,72 h) and increased GSH (125–2000µM, 24 h). U-NTAwas genotoxic (1000µM, 30 min) but did not inhibit therepair of DNA damage caused by hydrogen peroxide (H₂O₂), 4-hydroxynonenal,and 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]-pyridine.U-NTA was also genotoxic in LT97 cells and primary colon cells,where it additionally increased migration of TP53 into the comettail. In LT97 cells, 0.5–2mM U-NTA increased chromosomalaberrations in chromosomes 5, 12, and 17, which harbor the tumor-relatedgenes APC, KRAS, and TP53. It may be concluded that uraniumcompounds could increase alimentary genotoxic exposure in humansif they reach the food chain in sufficient amounts.     

Evaluation of cytotoxicity and genotoxicity of pesticide mixtures on lymphocytes

The cytotoxicity and genotoxicity of pesticide mixtures viz. endosulfan?+?chlorpyrifos, chlorpyrifos?+?profenofos, and endosulfan?+?profenofos were evaluated on cultured human peripheral blood lymphocytes using assays for cell viability, and genotoxicity using chromosomal aberrations test and comet assay. The LC₅₀ values for cytotoxicity were 3.50?μM, 4.18?μM, and 10.5?μM for profenofos, endosulfan, and chlorpyrifos respectively. When combined in equimolar concentrations, the LC₅₀ values for cytotoxicity were 1.4?μM, 1.8?μM, and 2.0?μM for endosulfan?+?chlorpyrifos, chlorpyrifos?+?profenofos, and endosulfan?+?profenofos, respectively. Higher concentrations of individual pesticides (0.5–4.0?μM) but very low concentrations of pesticide mixtures caused significant DNA damage. Additive index values indicated a synergistic effect of toxicity for endosulfan?+?chlorpyrifos combination (1.12 TTU). The binary mixture of chlorpyrifos?+?profenofos showed an additive toxicity (0.46 TTU) while an antagonistic effect was observed for endosulfan?+?profenofos combination. Synergism could be due to these complementary pesticides simultaneously acting in different ways, magnifying their efficacy, whereas an additive interaction would imply that the chemicals are acting by the same mechanism and at the same target. Analysis of toxicity of pesticide mixtures may serve as important biomarker for occupational and household exposure to pesticides, with different modes of action.     

Nanoscale zerovalent iron particles induce differential cytotoxicity,genotoxicity, oxidative stress and hemolytic responses in human lymphocytes and erythrocytes in vitro

The growing usage of nanoscale zerovalent iron particles (nZVI) in the remediation of soil, ground/surface water has elicited large‐scale environmental release triggering human exposure. The size of nanomaterials is a key regulator of toxicity. However, the effect of a variable size of nZVI on genotoxicity is unexplored in human cells. To the best of our knowledge, in this study, the cytotoxic, genotoxic and hemolytic potential of nZVI‐1 (15 nm) and nZVI‐2 (50 nm) at concentrations of 5, 10 and 20 μg/mL was evaluated for the first time in human lymphocytes and erythrocytes treated for 3 hours. In erythrocytes, spherocytosis and echinocytosis occurred upon exposure to nZVI‐1 and nZVI‐2, respectively, leading to hemolysis. Lymphocytes treated with 20 μg/mL nZVI‐2 and 10 μg/mL nZVI‐1, incurred maximum DNA damage, although nZVI‐2 induced higher cyto‐genotoxicity than nZVI‐1. This can be attributed to higher Fe ion dissolution and time/concentration‐dependent colloidal destabilization (lower zeta potential) of nZVI‐2. Although nZVI‐1 showed higher uptake, its lower genotoxicity can be due to lesser Fe content, Fe ion dissolution and superior colloidal stability (higher zeta potential) compared with nZVI‐2. Substantial accumulation of Ca²⁺, superoxide anions, hydroxyl radicals and H₂O₂ leading to mitochondrial impairment and altered antioxidant enzyme activity was noted at the same concentrations. Pre‐treatment with N‐acetyl‐cysteine modulated these parameters indicating the indirect action of reactive oxygen species in nZVI‐induced DNA damage. The morphology of diffused nuclei implied the possible onset of apoptotic cell death. These results validate the synergistic role of size, ion dissolution, colloidal stability and reactive oxygen species on cyto‐genotoxicity of nZVI and unlock further prospects in its environmental nano‐safety evaluation.     

A research on the genotoxicity of stevia in human lymphocytes

Stevia extracts are obtained from Stevia rebaudiana commonly used as natural sweeteners. It is ～250–300 times sweeter than sucrose. Common use of stevia prompted us to investigate its genotoxicity in human peripheral blood lymphocytes. Stevia (active ingredient steviol glycoside) was dissolved in pure water. Dose selection was done using ADI (acceptable daily intake) value. Negative control (pure water), 1, 2, 4, 8 and 16?μg/ml concentrations which were equivalent to ADI/4, ADI/2, ADI, ADI?×?2 and ADI?×?4 of Stevia were added to whole-blood culture. Two repetitive experiments were conducted. Our results showed that there was no significant difference in the induction of chromosomal aberrations and micronuclei between the groups treated with the concentrations of Stevia and the negative control at 24 and 48?h treatment periods. The data showed that stevia (active ingredient steviol glycosides) has no genotoxic activity in both test systems. Our results clearly supports previous findings.     

An alkaline comet assay study on the antimalarial drug atovaquone in human peripheral blood lymphocytes: a study based on clinically relevant concentrations

Atovaquone, a hydroxynaphthoquinone, is an anti‐parasite drug, selectively targeting the mitochondrial respiratory chain of malaria parasite. It is used for both the treatment and prevention of malaria, usually in a fixed combination with proguanil. Although atovaquone has not often been associated with severe adverse reactions in the recommended dosages and has a relatively favorable side effect profile, the present study was undertaken to evaluate its cytogenotoxic potential towards human peripheral blood lymphocytes. Two different concentrations of atovaquone found in plasma when used in fixed‐dose combination with proguanile hydrochloride were used with and without S9 metabolic activation: 2950 ng ml^?1 used for prophylactic treatment and 11 800 ng ml^?1 used in treatment of malaria. The results showed that lymphocyte viability was not affected after the treatment, suggesting that atovaquone was not cytotoxic in the given concentrations. With the alkaline comet assay we demonstrated that in human peripheral blood lymphocytes no significant changes in comet parameters occurred after the treatment. There were no differences in tested parameters with the addition of S9 metabolic activation, indicating that atovaquone either has no metabolite or it is not toxic in the given concentrations. Since no effects were observed after the treatment, it is to be concluded that atovaquone is safe from the aspect of genototoxicity in the recommended dosages. Copyright © 2011 John Wiley & Sons, Ltd.     

The in vitro genotoxic and cytotoxic effects of remeron on human peripheral blood lymphocytes

Remeron (Mirtazapine) is an antidepressant drug which exerts its action by blocking presynaptic α-2-adrenergic receptors and postsynaptic serotonin types 2 and 3 receptors. In this in vitro analysis, human peripheral blood lymphocytes was treated by remeron (10, 25, 40 and 55 μg/mL) for 24 hours and 48 hours periods, then it was attempted to study of genotoxic and cytotoxic effects of the substance on human peripheral blood lymphocytes by some tests such as sister chromatid exchange (SCE), chromosomal abnormalities (CA) and micronucleus (MN) tests. Also proliferating effect of the substance was investigated. Remeron didn’t significantly cause chromosomal abnormalities and sister chromatid exchange while caused micronucleus at 40 μg/mL concentration and 24?h periodic time and increased proliferation index of the both 24 and 48 hours treated cells was decreased in a concentration manner. Also, exposing to the remeron for 24 and 48 hours leaded to a decrease in mitotic index and nucleus division index in the cells by concentration dependent manner. These findings showed that remeron did not have significantly genotoxic effects on human peripheral blood lymphocytes while it showed cytotoxic effects on the cells, which is the first report on genotoxic and cytotoxic properties of remeron.     

Assessment of the genotoxic effects of organophosphorus insecticides phorate and trichlorfon in human lymphocytes

In vitro genotoxic effects of organophosphorus insecticides Phorate (PHR) and Trichlorfon (TCF) were investigated using four genotoxicity endpoints. Different concentration ranges between 0.25–2.00 μg mL^?1 of PHR and 2.34–37.50 μg mL^?1 of TCF were applied to lymphocytes. PHR and TCF significantly increased the frequency of chromosomal aberrations (except 2.34 μg mL^?1 for TCF) and sister chromatid exchanges at all treatment times and concentrations. Most of the used concentrations induced a significant increase in the frequency of micronuclei. Furthermore, PHR and TCF significantly decreased the mitotic index at the higher concentrations after 24‐ and 48‐h treatments. In the comet assay, PHR and TCF significantly increased the comet tail at all concentrations. However, the comet tail intensity was significantly increased at only the highest concentration of PHR and at all concentrations of TCF. According to these results, PHR and TCF possess clastogenic, mutagenic, and DNA damaging effects in human lymphocytes in vitro. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 577–587, 2014.     

Effect of size and shape on toxicity of zinc oxide (ZnO) nanomaterials in human peripheral blood lymphocytes

The multi-industrial applications of zinc oxide nanomaterials (ZnO NMs) lead to increasing exposure to humans. Though the ZnO nanoparticles (NPs) toxicity had been evaluated previously, toxicity of other forms of ZnO nanomaterials has not been evaluated. In this study, cytotoxicity and genotoxicity of four different types of ZnO NMs were evaluated using human peripheral blood lymphocytes (HPBL). In addition, the effect of anti-oxidants on ZnO NMs induced toxicity was also evaluated. Our results suggest that, size and shape of the nanomaterials have profound effects on their toxicity. The NPs and nanorods (NRs) possessed higher level of oxidative potential and ROS generation capacity than microparticles (MPs) and microrods (MRs). In contrast, MPs and MRs possessed higher level of lipid peroxidation capacity. The smaller NPs are more genotoxic while larger MPs and MRs were more cytotoxic in nature. Treatment with vitamin C or Quercetin significantly reduces the genotoxicity associated with ZnO NMs. The influence of size and shape in mediating NMs toxicity should be taken into account and the possible supplementation of anti-oxidants might mitigate the toxicity.