Mehmet Topaktas

Chromosome aberrations and sister chromatid exchanges in cultured human lymphocytes treated with sodium metabisulfite, a food preservative

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 microg/ml) and treatment periods (24 and 48h) dose-dependently. However, SMB decreased the replication index (RI) and the mitotic index (MI) at the concentrations of 150 and 300 microg/ml for 24 and 48h treatment periods. This decrease was dose-dependent as well.

Genotoxicity of Aspartame

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 µg/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 TA100 strains in the absence and presence of S9 mix.

The in vitro genotoxic effects of a commercial formulation of α‐cypermethrin in human peripheral blood lymphocytes

α‐Cypermethrin, a highly active pyrethroid insecticide, is effective against a wide range of insects encountered in agriculture and animal husbandry. The potential genotoxicity of a commercial formulation of α‐cypermethrin (Fastac 100 EC, containing 10% α‐cypermethrin as the active ingredient) on human peripheral lymphocytes was examined in vitro by sister chromatid exchange (SCE), chromosomal aberrations (CAs), and micronucleus (MN) tests. The human lymphocytes were treated with 5, 10, 15, and 20 μg/ml of α‐cypermethrin for 24‐ and 48‐hr. α‐Cypermethrin induced SCEs and CAs significantly at all concentrations and treatment times and MN formation was significantly induced at 5 and 10 μg/ml of α‐cypermethrin when compared with both the control and solvent control. Binuclear cells could not be detected sufficiently in the highest two concentration of α‐cypermethrin (15 and 20 μg/ml) for both the 24‐ and 48‐hr treatment times. α‐Cypermethrin decreased the proliferation index (PI) at three high concentrations (10, 15, and 20 μg/ml) for both treatment periods as compared with the control groups. In addition, α‐cypermethrin reduced both the mitotic index (MI) and nuclear division index (NDI) significantly at all concentrations for two treatment periods. The PI and MI were reduced by α‐cypermethrin in a concentration‐dependent manner during both treatment times. In general, α‐cypermethrin showed higher cytotoxic and cytostatic effects than positive control (MMC) at the two highest concentrations for the 24‐ and 48‐hr treatment periods. The present study is the first to report the genotoxic and cytotoxic effects of commercial formulation of α‐cypermethrin in peripheral blood lymphocytes. Environ. Mol. Mutagen., 2009.

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.

Genotoxic potential of cyfluthrin

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 microg/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 microg/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.

In vivo chromosomal aberrations in bone marrow cells of rats treated with Marshal

In this study, the cytogenetic effects of Marshal (insecticide/nematocide) were investigated in bone marrow cells of rats. The results obtained from animals treated with Marshal were compared with the results of animals treated with ethyl carbamate (EC) and with controls. Concentrations of 12.5, 25 and 50 mg/kg b.wt. of Marshal and 100, 200 and 400 mg/kg b.wt. of EC were used and animals were sampled at three different times (6, 12 and 24 h). Marshal increased the number of chromosomal aberrations (CA) per cell, and the number of cells with abnormalities, at all concentrations and treatment times. Generally, Marshal could increase the number of the abnormal cells and the formation of CA as easily as EC. However, Marshal, at 50 mg/kg b.wt. did not increase the frequency of abnormal cells or CA as strongly as EC, at 400 mg/kg b.wt. for 6 h. Marshal also decreased the mitotic index (MI) compared with the control group. The MI was higher in the group treated with Marshal for 6 h than that treated with EC. However, the effects of Marshal and EC on the MI in the groups treated for 12 and 24 h were similar. We found that the effect of Marshal on the formation of abnormal cells and CA was dependent on concentration and treatment time.

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.

Chromosome numbers of four Pistacia (Anacardiaceae) species

Summary There is little cytological information for Pistacia species in the literature and they are old or require confirmation. This study aims to adapt a chromosome count procedure for Pistacia species and to determine chromosome numbers of four Pistacia species in root tip cells. Chromosome counts were performed for P. vera L., P. terebinthus L., P. atlantica Desf. and in a new species P. eurycarpa Yalt., which have been characterized at the molecular level. Dehulled Pistacia nuts were stratified and treated with 500 ppm GA3 and then germinated on plates. Growing root tips were used for counting at c-metaphase of mitosis cells. A good chromosome counting procedure was established for Pistacia species that provided well-spread and well-stained chromosome at metaphase of mitosis. Chromosome numbers of all four Pistacia species were found to be 2n = 30. Chromosome numbers of P. atlantica and P. eurycarpa (syn. P. atlantica subsp. kurdica) species are reported here for the first time as 2n = 30. This study provides important information on pistachio cultivars/rootstocks for breeders and cytogeneticists.

The genotoxic effect of potassium metabisulfite using chromosome aberration, sister chromatid exchange, micronucleus tests in human lymphocytes and chromosome aberration test in bone marrow cells of rats

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 marrow cells of rats were investigated. The human lymphocytes were treated with 25, 50, 100, and 200 μg/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. Environ. Mol. Mutagen., 2008.

Confirmation of the Chromosome Damaging Effects of Lamivudine in In Vitro Human Peripheral Blood Lymphocytes

The aim of this study was to investigate genotoxic effects of lamivudine (an analogue of cytidine) using in vitro sister chromatid exchange (SCE), chromosome aberration (CA), and micronucleus (MN) tests in human peripheral lymphocytes. The cells were treated with 75, 100, 125, and 150 μg/ml concentrations of lamivudine (roughly 30–60 times higher than plasma levels achieved in patients receiving this drug) for two (24‐ and 48‐hr) treatment periods. Lamivudine induced SCEs at the highest concentration (150 μg/ml) in the 24‐hr treatment, and at 125 and 150 μg/ml in the 48‐hr treatment, when compared to the solvent control. During both treatment periods, structural chromosome aberrations were significantly increased at 100, 125, and 150 μg/ml lamivudine concentrations. However, the increases of SCEs (22%) and CAs (50%) were weak. In addition, lamivudine reduced both the proliferation index (PI) and the mitotic index (MI) significantly at all concentrations for the two treatment periods. The MI was reduced by lamivudine in a dose‐dependent manner during both the 24‐ and 48‐hr treatment periods. In contrast, the PI was reduced by lamivudine only during the 48‐hr treatment period. A weak but significant increase in MN formation was observed following lamivudine treatment at 100, 125, and 150 μg/ml for 48 hr, but no significant increase in micronuclei were observed following 24‐hr treatment. In conclusion, lamivudine has a weak genotoxic effect at elevated doses on human peripheral lymphocytes. Environ. Mol. Mutagen., 2008.