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In a previous study, 3-amino-4-[4-(dimethylamino)phenyl]-4,5-dihydro-1,2,5-thiadiazole 1,1-dioxide (DPTD), which is five-membered cyclosulfamide, was synthesized and structurally characterized. The aim of this study was to investigate the cytotoxic and genotoxic effects of DPTD on cultured human lymphocytes in the presence and absence of a metabolic activation system (S9 mix). The cytotoxicity and genotoxicity of DPTD in human peripheral blood lymphocytes were examined in vitro by using chromosomal aberration (CA) and micronucleus (MN) tests. Mitomycin-C (MMC) for cultures without S9 mix and cyclophosphamide monohydrate (CP) for cultures with S9 mix were used as positive controls. The cultures were treated with DPTD (45, 90, and 180??g/mL) in the absence and presence of S9 mix. The cells were also co-treated with DPTD together with MMC or CP. DPTD showed cytotoxic activity due to decreases in mitotic index (MI) and nuclear division index (NDI) in the absence and presence of S9 mix. DPTD also increased the CAs, aberrant cells with CAs and MN values in cultures with and without S9 mix. When DPTD and MMC or CP were used together, lower MI and NDI values and higher CA and MN values were found than those DPTD treated alone. Both DPTD and its metabolites have cytotoxic, cytostatic and genotoxic potential on human peripheral blood lymphocyte cultures under the experimental conditions. Furthermore, co-treatment of DPTD and MMC or CP can cause more cytotoxicity and genotoxicity. Our results indicated that the use of DPTD with other chemotherapeutic drugs may display more effective results.

Acrolein (AC), a highly reactive hazardous pollutant, poses serious threats to human health. Whey protein (WP) and conjugated linoleic acid (CLA) have beneficial health implications. We investigated the protective effects of WP and CLA against AC-induced toxicity in rats. The animals were orally gavaged with CLA (200 mg/kg/day), WP (200 mg/kg/day), AC (5 mg/kg/day), CLA + AC (200 + 5 mg/kg/day), and WP + AC (200 + 5 mg/kg/day) six days per week for 30 days. The oral administration of AC significantly induced oxidative stress by increasing thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PCOs) levels and decreasing glutathione (GSH) level in the spleen, thymus, and polymorphonuclear leukocytes (PMNs). It also increased the frequencies of micronucleus (MN) and megakaryocytic emperipolesis (ME) and decreased the ratio of polychromatic erythrocytes (PCEs) in bone marrow. Slight alterations in urinary 8-hydroxydeoxyguanosine (8-OHdG) levels were not significant. Co-treatment with CLA + AC or WP + AC ameliorated the values of oxidative stress, MN, PCE, and ME. These data suggest that CLA and WP can improve the antioxidant defenses and preclude the formation of genetic damage and ME.

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 significantly 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.

Clothianidin (CHN) is a broad-spectrum neonicotinoid insecticide. Limited studies have been carried out on the cytotoxic and genotoxic effects of both CHN using different genotoxicity tests in human cells with or without human metabolic activation system (S9 mix). Therefore, the aim of this study is to investigate the cytotoxic and genotoxic effects of CHN and its metabolites on human lymphocyte cultures with or without S9 mix using chromosomal aberration (CA) and micronucleus (MN) tests. The cultures were treated with 25, 50, and 100 µg/ml of CHN in the presence (3 h treatment) and absence (48 h treatment) of S9 mix. Dimethyl sulfoxide (DMSO) was used as a solvent control. CHN showed cytotoxic and genotoxic effects due to significant decreases in mitotic index (MI) and nuclear division index (NDI), and significant increases in the CAs, aberrant cells, and MN formation in the absence of S9 mix when compared with solvent control. However, CHN did not significantly induce cytotoxicity and genotoxicity in the presence of S9 mix. Our results indicated that CHN has cytotoxic, cytostatic, and genotoxic potential on human peripheral blood lymphocyte cultures, but not its metabolites under the experimental conditions.

WOS: 000406544200008 PubMed: 27894189 It has been stated that some antipsychotic drugs might cause genotoxic and carcinogenic effects. Ziprasidone (ZIP) is commonly used an antipsychotic drug. However, its genotoxicity and carcinogenicity data are very limited. The cytotoxicity and genotoxicity of ZIP on human peripheral blood lymphocytes were examined in vitro by sister chromatid exchange (SCE), chromosome aberration (CA) and micronucleus (MN) tests in this study. Lymphocyte cultures were treated with 50, 75 and 100 mg/ml of ZIP in the presence and absence of a metabolic activator (S9 mix). Dimethylsulfoxide was used as a solvent control. While the cells were treated with ZIP for 24 h and 48 h in cultures without S9 mix, the cultures with S9 mix were exposed to ZIP for 3 h. ZIP and its metabolites can exert cytotoxic activities due to significant decreases in mitotic index, proliferation index and nuclear division index in the presence and absence of S9 mix. Statistically significant increases in CAs, aberrant cells and MN values in the presence and absence of S9 mix were found in cultures treated with ZIP. While ZIP significantly increased the SCE values in the absence of S9 mix at all concentrations, increased SCE values in cultures with S9 mix were not found to significantly at all concentrations tested. Our results indicated that both ZIP and its metabolites have cytotoxic, cytostatic and genotoxic potential on lymphocyte cultures under the experimental conditions. Further studies are necessary to make a possible risk assessment in patients receiving therapy with this drug. Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) We would like to thank to The Scientific and Technological Research Council of Turkey (TUBITAK) for the financial support of this work.

Loratadine (LOR) is a new generation antihistamine used in the treatment of allergic disorders.The aim of this study was to evaluate the cytogenotoxic effect of LOR on human peripheral blood lymphocytes.We investigated the genotoxic effect of this drug in cultured human peripheral blood lymphocytes using sister chromatid exchange (SCE), chromosomal aberrations (CA) and micronucleus (MN) assay in culture conditions. Proliferation index (PI), mitotic index (MI) and nuclear division index (NDI) were also calculated to determine the cytotoxic/cytostatic effect. Cultures were treated with LOR at three concentrations (5, 15 and 25 µg/ml) for 48 h.Although the MI significantly decreased at the higher concentrations (15 and 25 µg/ml) compared with negative (solvent) control, LOR indicated weaker cytotoxic potential in PI and NDI values at all the tested concentrations. LOR increased the frequencies of SCE, CA and MN in all lymphocyte cultures. However, significant increase was observed in MN at the medium and highest doses (15 and 25 µg/ml) and in CA at the medium dose (15 µg/ml) compared with negative (solvent) control culture. Our results indicate that LOR has cytotoxic and genotoxic effects on human peripheral blood lymphocyte cultures.Although most of previously findings have shown that LOR does not reflect genotoxicity, our results indicated that it may be a genotoxic drug.More studies are necessary to elucidate the relationship between cytotoxic, genotoxic and apoptotic effects, and to make a possible risk assessment in patients receiving therapy with this drug.

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.