Chromosomal aberrations in cultured human lymphocytes treated with the fungicide, Thiram

In vitro effects of different concentrations of Thiram were tested on human lymphocytes to determine, by means of the chromosome aberrations (CAs) assay, whether this fungicide could induce clastogenic damage. Evidences of the effect of Thiram on human lymphocytes were limited to sister chromatid exchange, micronuclei formation, and comet assays. We evaluated 0.01, 0.1, 1.2, and 12.0 μg/mL of Thiram, where 0.01 μg/mL represent the acceptable daily intake dose set by the World Health Organization and the Food and Agriculture Organization for fruit and vegetables, whereas 0.1, 1.2, and 12.0 μg/mL are its multiple values. Results indicated that human lymphocytes treated in vitro with Thiram at concentrations of 1.20 and 12.0 μg/mL significantly increased CAs frequency, compared with the negative control, whereas at lower concentrations (0.01 and 0.1 μg/mL), this effect was not observed. However, Thiram showed a clastogenic effect also at the concentration value of 1.2 μg/mL that represents a lower value with respect to the residue limits found in Italy for grapes, strawberries, potatoes, tobacco, and other fruits and vegetables. Finally, according to some evidence obtained from the study of other fungicides, Thiram produced a significant reduction in the mitotic index with increasing concentration.     

Evaluation of cytogenetic and DNA damage induced by the antidepressant drug-active ingredients,trazodone and milnacipran,in vitro

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.     

In vitro investigation of the genotoxic and cytotoxic effects of thiacloprid in cultured human peripheral blood lymphocytes

Thiacloprid, a neonicotinoid insecticide, is widely used for controlling various species of pests on many crops. The potential genotoxic effects of thiacloprid on human peripheral blood lymphocytes (PBLs) were investigated in vitro by the chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and cytokinesis‐block micronucleus (MN) assays. The human PBLs were treated with 75, 150, and 300 μg/mL thiacloprid in the absence and presence of an exogenous metabolic activator (S9 mix). Thiacloprid increased the CAs and SCEs significantly at all concentrations (75, 150, and 300 μg/mL) both in the absence and presence of the S9 mix and induced a significant increase in MN and nucleoplasmic bridge formations at all concentrations for 24 h and at 75 and 150 μg/mL for 48‐h treatment periods in the absence of the S9 mix; and at all concentrations in the presence of the S9 mix when compared with the control and solvent control. Thiacloprid was also found to significantly induce nuclear bud (NBUD) formation at 300 μg/mL for 24 h and at 150 μg/mL for 48‐h treatment times in the absence of the S9 mix and at the two highest concentrations (150 and 300 μg/mL) in the presence of the S9 mix. Thiacloprid significantly decreased the mitotic index, proliferation index, and nuclear division index for all concentrations both in the absence and presence of the S9 mix. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 631–641, 2014.     

Genotoxic effects of a particular mixture of acetamiprid and α‐cypermethrin on chromosome aberration,sister chromatid exchange,and micronucleus formation in human peripheral blood lymphocytes

The genotoxic effects of a particular mixture of acetamiprid (Acm, neonicotinoid insecticide) and α‐cypermethrin (α‐cyp, pyrethroid insecticide) on human peripheral lymphocytes were examined in vitro by chromosomal aberrations (CAs), sister chromatid exchange (SCE), and micronucleus (MN) tests. The human peripheral lymphocytes were treated with 12.5 + 2.5, 15 + 5, 17.5 + 7.5, and 20 + 10 μg/mL of Acm+α‐cyp, respectively, for 24 and 48 h. The mixture of Acm+α‐cyp induced the CAs and SCEs at all concentrations and treatment times when compared with both the control and solvent control and these increases were concentration‐dependent in both treatment times. MN formation was significantly induced at 12.5 + 2.5, 15 + 5, 17.5 + 7.5, μg/mL of Acm+α‐cyp when compared with both controls although these increases were not concentration‐dependent. Binuclear cells could not be detected sufficiently in the highest concentration of the mixture (20 + 10 μg/mL) for both the 24‐ and 48‐h treatment times. Mitotic index (MI), proliferation index (PI) and nuclear division index (NDI) significantly decreased because of the cytotoxic and cytostatic effects of the mixture, at all concentrations for two treatment periods. Significant decreases in MI and PI were concentration dependent at both treatment times. The decrease in NDI was also concentration‐dependent at 48‐h treatment period. In general, Acm+α‐cyp inhibited nuclear division more than positive control, mitomycin C (MMC) and showed a higher cytostatic effect than MMC. Furthermore, in this article, the results of combined effects of Acm+α‐cyp were compared with the results of single effects of Acm or α‐cyp (Kocaman and Topaktas, 2007 , 2009 , respectively). In conclusion, the particular mixture of Acm+α‐cyp synergistically induced the genotoxicity/cytotoxicity in human peripheral blood lymphocytes. © 2009 Wiley Periodicals, Inc. Environ Toxicol, 2010.     

The Assesment of Genotoxicity of Carbamazepine Using Cytokinesis-Block (CB) Micronucleus Assay in Cultured Human Blood Lymphocytes

The genotoxic effect of CBZ has been investigated in few studies. There is little evidence linking carbamazepine (CBZ) with any genotoxic effects, particularly in vitro micronucleus test using cytogenesis-block technique. In this study, the genotoxicity of the antiepileptic drug, carbamazepine, was tested using cytokinesis-block (CB) micronucleus assay. In vitro analysis was performed in human blood lymphocytes from four healthy persons at five different concentrations of carbamazepine (6, 8, 10, 12, 14 μg/mL). Genotoxic potential and cytotoxic effects of carbamazepine were evaluated by using micronucleus assay and cytokinesis-block proliferation index (CBPI), called the parameter of cytotoxicity in human peripheral blood lymphocyte cultures, respectively. The results of this study indicate that CBZ caused the genotoxic effect under in vitro conditions, except at the dose of 6 μg/mL, and cytotoxic effects of carbamazepine were revealed by a decrease in the cytokinesis-block proliferation index at all the concentrations.     

Micronuclei,nucleoplasmic bridges,and nuclear buds induced in human lymphocytes by the fungicide signum and its active ingredients (boscalid and pyraclostrobin)

The aim of this study was to investigate the genotoxic and cytotoxic potential of the Signum fungicide and its active ingredients (boscalid and pyraclostrobin) on human peripheral blood lymphocytes using the cytokinesis‐block micronucleus (CBMN) assay. Micronuclei (MNi), nucleoplasmic bridges (NPBs), nuclear bud (NBUDs) formations, and the cytokinesis‐block proliferation index (CBPI) were evaluated in treated lymphocytes in Go (cells were treated and then kept in culture without stimulation for 24 h) and proliferation phases (cells were treated after 44 h culture in medium containing phytohemagglutinin). MN formation in lymphocytes treated in G₀ statistically increased at doses of 2, 6, and 25 μg/mL signum; 0.5 and 2 μg/mL boscalid; and 0.5, 1.5, and 2 μg/mL pyraclostrobin; while NPB formation increased at a dose of 0.25 μg/mL pyraclostrobin. All concentrations of each fungicide did not statistically increase NBUD formation, while the cytotoxicity increased the dependent on concentration in lymphocytes treated in G₀. Doses of 0.5, 1, 1.5, and 3 μg/mL signum; 0.5, 1, and 1.5 μg/mL boscalid; and 0.75 μg/mL pyraclostrobin statistically increased the MN formation in proliferating lymphocytes. NPB formation increased in proliferating lymphocytes at doses of 1, 1.5, 2, and 3 μg/mL signum and at a dose of 0.75 μg/mL pyraclostrobin. In addition, a dose of 0.75 μg/mL pyraclostrobin increased NBUD frequencies. Cytotoxicity increased with increasing concentrations of each fungicide. It is concluded that signum, boscalid, and pyraclostrobin may be genotoxic and cytotoxic in vitro human peripheral blood lymphocytes in consideration of each of the two protocols. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 723–732, 2014.     

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.     

Effects of natamycin on sister chromatid exchanges,chromosome aberrations and micronucleus in human lymphocytes

Natamycin (pimaricin) (E235) is an antifungal that can be used as an antibiotic to treat most fungus infections. It has been globally used in a variety of foods and beverages. In the present study, the effects of natamycin on chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and micronucleus (MN) formation in human lymphocytes cells were investigated. The human lymphocytes were treated with 13, 18, 23, and 28 μg/mL of natamycin for 24 and 48 h. Natamycin induced the SCE frequency at the highest concentration for 48 h only; however, it induced the structural CA and MN frequency at all concentrations when compared to control and at all concentrations, except the lowest concentration (13 μg/mL), when compared to solvent control. Natamycin showed a cytotoxic effect by decreasing the replication index, mitotic index, and nuclear division index (NDI), especially at the highest concentrations for two treatment periods.     

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.     

The Effects of Food Protector Biphenyl on Sister Chromatid Exchange,Chromosome Aberrations,and Micronucleus in Human Lymphocytes

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).     

Genotoxicity Assessment of HM10620 Containing Recombinant Human Interferon-α

HM10620 is a recombinant human interferon-α (rhIFN-α) linked to immunoglobulin via N-terminal–specific non-peptidyl polyethylene glycol linker to improve the in vivo stability of interferon. Potential genotoxic effects of HM10620 in three short-term mutagenicity assays were investigated, which included the Ames assay, in vitro chromosomal aberration assay, and the in vivo micronucleus assay. HM10620 did not cause any mutation in the Ames assay tested using five tester strains at six concentrations of 6.25, 12.5, 25, 50, 100, and 200 μg/plate. To assess clastogenic effect, the in vitro chromosomal aberration assay and the in vivo micronucleus assay were performed using Chinese hamster lung cells and male ICR mice, respectively. Chromosomal aberration was not induced at the concentrations of 10, 20, and 40 μg/mL. Also, there was no difference in the incidence of micronucleated polychromatic erythrocytes at doses of 10, 20, and 40 mg/kg in male mice compared with the vehicle control group. Therefore, based on the results obtained from the three studies, it is concluded that HM10620 is not a mutagenic agent in bacterial cells and causes no chromosomal damage in mammalian cells both in vitro and in vivo.     

Cytogenetic alterations in human lymphocyte cultures following exposure to ofloxacin

Ofloxacin (OFX), a second-generation of quinolones, is a broad-spectrum flouroquinolone antibiotic used in the treatment of various bacterial infections. In this article, we aimed to investigate the cytotoxic and genotoxic potentials of OFX in cultured human peripheral lymphocytes. The cytotoxicity and genotoxicity of OFX on human peripheral blood lymphocytes were examined in vitro by sister chromatid exchange (SCE), chromosomal aberrations (CAs) and micronucleus (MN) tests. Cultures were treated with 30, 60 and 120?μg/ml of OFX for 48?h. Dimethylsulfoxide (DMSO) was used as a solvent control. OFX decreased the mitotic index (MI) and nuclear division index (NDI) significantly, especially at higher concentrations (60 and 120?μg/ml) compared with solvent control. OFX signi?cantly induced CAs at all concentrations and SCEs at higher concentrations (60 and 120?μg/ml) compared with solvent control. In conclusion, our results indicated that OFX has cytotoxic, cytostatic and genotoxic potential especially at higher concentrations on human peripheral blood lymphocyte cultures under the experimental conditions.     

Genotoxicity of monosodium glutamate

Monosodium glutamate (MSG) is one of the most widely used flavor enhancers throughout the world. The aim of this study is to investigate the genotoxic potential of MSG by using chromosome aberrations (CAs), sister-chromatid exchanges (SCEs), cytokinesis-blocked micronucleus (CBMN), and random amplified polymorphic DNA-polimerase chain reaction (RAPD-PCR) in cultured human lymphocytes and alkaline comet assays in isolated human lymphocytes, which were incubated with six concentrations (250, 500, 1000, 2000, 4000 and 8000 μg/mL) of MSG. The result of this study indicated that MSG significantly and dose dependently increased the frequencies of CAs, SCE and MN in all treatments and times, compared with control. However, the replication (RI) and nuclear division indices (NDI) were not affected. In this paper, in vitro genotoxic effects of the MSG was also investigated on human peripheral lymphocytes by analysing the RAPD-PCR with arbitrary 10-mer primers. The changes occurring in RAPD profiles after MSG treatment include increase or decrease in band intensity and gain or loss of bands. In the comet assay, this additive caused DNA damage at all concentrations in isolated human lymphocytes after 1-h in vitro exposure. Our results demonstrate that MSG is genotoxic to the human peripheral blood lymphocytes in vitro.     

Evaluation of genotoxic effects of 3-methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione on human peripheral lymphocytes

Context: Tranexamic acid is commonly used for curing abnormal bleeding in a variety of diseases. In a previous study, 12 different tetrahydro-2H-1,3,5-thiadiazine derivatives were synthesized from the amine group of tranexamic acid. Their antifibrinolytic and antimicrobial activities were compared with tranexamic acid. 3-Methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione (3-MTTT) was the most remarkable one, which may be used as a drug.

Objectives: In vitro genotoxicity of 3-MTTT was investigated using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronucleus (MN) and comet assays.

Materials and methods: Various concentrations 0.78, 1.56, 3.13, 6.25, 12.50 and 25.00?μg/mL of 3-MTTT were applied to lymphocytes obtained from two donors for periods of 24 and 48?h. A negative (distilled water), a solvent (2:1 PBS:10% NaOH for cultured lymphocyte, and PBS for isolated lymphocytes) and a positive control (MMC for cultured lymphocytes and H₂O₂ for isolated lymphocytes) were also maintained.

Results: While this compound did not increase the frequency of abnormal cells and CA/cell ratio compared to negative control (except 48?h, 25?μg/mL), it significantly increased the frequency of SCEs at the four highest concentrations at both treatment periods (except 6.25?μg/mL, 48?h). It significantly decreased the MI in all the concentrations at 24?h (except 0.78?μg/mL) and in the highest three concentrations at 48?h. This compound did not significantly increase the frequency of MN and DNA damage compared to negative control. This compound did not affect the replication and nuclear division index.

Discussion and conclusion: Our results demonstrated that this compound does not represent a significant risk at the genetic level in in vitro human lymphocytes.     

Effects of water extract of Cajanus cajan leaves on the osteogenic and adipogenic differentiation of mouse primary bone marrow stromal cells and the adipocytic trans-differentiation of mouse primary osteoblasts

The effects of water extract of Cajanus cajan (Linn.) Millsp. (Leguminosae) leaves (WECML) on the osteogenic and adipogenic differentiation of mouse primary bone marrow stromal cells (BMSCs) and the adipocytic trans-differentiation of mouse primary osteoblasts (OBs) were studied. The results indicated that WECML promoted the proliferation of BMSCs and OBs at most concentrations. WECML promoted the osteogenic differentiation and formation of mineralized matrix nodules of BMSCs at concentrations of 0.1, 1, and 10 μg/mL, but inhibited the osteogenic differentiation and formation of mineralized matrix nodules of BMSCs at concentration of 0.01 μg/mL. WECML inhibited the adipogenic differentiation of BMSCs and adipocytic trans-differentiation of OBs at concentrations of 0.001, 0.1, 1, 10, and 100 μg/mL, but had no effects at concentration of 0.01 μg/mL. The results suggest that WECML has protective effects on bone and these protective effects may be mediated by decreasing adipocytic cell formation from BMSCs, which may promote the proliferation, differentiation, and mineralization function of OBs. The defined active ingredients in the WECML and the active mechanism need to be further studied.     

Assessment of genomic damage and repair on human lymphocytes by paint thinner in vitro

Paint thinners are organic-solvent complex mixtures frequently used by car painters around the world in industries and shops. Some studies have revealed the oxidative effect induced by thinner inhalation; however, its genotoxic effect is poorly studied. The aim of this study was to assess the cytotoxicity, genomic damage and DNA repair in vitro induced by commercial paint thinner 0.14 in human lymphocytes. Cytotoxicity was determined by cell-viability analysis with trypan blue after 4?h treatment with different thinner concentrations (0.025 to 1.2?µL/mL). Genomic damage was evaluated by means of the alkaline single-cell gel electrophoresis (SCGE; pH > 13) in treated cultures after 1?h with three low-cytotoxic thinner concentrations (0.05, 0.1 and 0.2?µL/mL). In order to evaluate the genomic DNA repair, one set of SCGE slides was prepared immediately after treatment, and another one was prepared after 4?h of liquid-holding recovery. A significant level of cytotoxicity was observed over the entire concentration range of paint thinner in lymphocytes (F?=?175.98; p?≤?0.001). In the SCGE % tail DNA assessment, a significant increase of lymphocyte genomic damage was evidenced (F?=?72.32; p?p?相似文献   

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.     

In vitro cytogenetic and genotoxic effects of curcumin on human peripheral blood lymphocytes

Curcumin has shown a wide range of properties such as anti-inflammatory and anti-carcinogenic properties. Many of these effects, mainly the anti-carcinogenic effect, could be linked to its anti-oxidant effects. Nevertheless, some studies suggest that this natural compound possesses both pro- and anti-oxidative effects and that curcumin could be a genotoxic agent for some cell lines. We evaluated the genetic damage induced by curcumin to human lymphocytes exposed to increasing concentrations (0–50 μg/ml) of curcumin. Biomarkers such as chromosome aberrations (CAs) and sister chromatid exchange (SCE) were analyzed. In addition to the cytogenetic analysis, the effect of curcumin in the cell proliferation kinetics (CPK) by the proliferation index (PI) was also analyzed. The results indicated that high concentrations of curcumin induced CAs, mainly acentric fragments. SCEs rate was not statistically different from the control group in any curcumin treated cell group. The PI of cells treated with 2 and 5 μg/ml of curcumin were statistically significant from the control group and finally, the MI showed a tendency to increase in all the concentrations of curcumin tested. In conclusion, it can be assumed that the higher concentrations of curcumin evaluated have a cyto and genotoxic effect, in vitro, for human peripheral lymphocytes.     

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.     

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.