Berrin Ayaz Tüylü

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.

Synthesis and mutagenicity of 2-aryl-substitute (o-hydroxy-, m-bromo-, o-methoxy-, o-nitro-phenyl or 4-pyridyl) benzothiazole derivatives on Salmonella typhimurium and human lymphocytes exposed in vitro

Derivatives of 2-aryl-substitute (o-hydroxy-, m-bromo-, o-methoxy-, o-nitro-phenyl or 4-pyridyl) benzothiazole were synthesized and tested for their mutagenicity in in vitro assays: (i) in the Ames test with Salmonella typhimurium TA98 and TA100 strains; and (ii) in the sister chromatid exchange (SCE) in cultured human lymphocytes. The four of compounds (BT-11, B-12, BT-14 and BT-15) caused statistically significant increase in revertant colonies of TA98 and TA100. Treatment of lymphocytes with compounds also caused a significant increase in SCE/cell in association with high levels and long exposure (300 µg/mL and 48 h) of the four compounds. It can be concluded that benzothiazole derivatives showed mutagenic activity and were also able to exert a genotoxic effect reducing both the replication index and mitotic index.

Synthesis and characterization of a new macrocyclic ligand and its copper (II), cadmium (II), and lead (II) complexes : Genotoxic activity of these complexes in cultured human lymphocytes

A new macrocyclic ligand 1,1′-bis(bis-(6,6′-oxymethylenyl-2,2′-bipyridine) binaphthyl, (L), and its complexes CuL(ClO4)2, CuL(NO3)2·3H2O, CdL(ClO4)2, and PbL(ClO4)2 have been synthesized and characterized on the basis of IR, 1H NMR, 13C NMR, FAB mass, and elemental analyses. Genotoxicity of these metal complexes has also been investigated by cytokinesis-blocked micronucleus assay in cultured human lymphocytes. Blood cultures were set up from two healthy donors, and treatment was done with different test concentrations for 24 and 48 h. The current results indicate that all compounds caused cytotoxicity by decreasing the cell number at the 150 μg/mL doses for 48-h treatments. On the other hand, CuL(ClO4)2, CuL(NO3)2·3H2O and PbL(ClO4)2 exhibited genotoxicity by inducing the number of micronucleated cells at doses of 150 μg/mL for 24-h treatments, but CdL(ClO4)2 did not significantly alter micronucleus induction. Hence, some test compounds may act as mutagens or produce clastogenic effects depending upon their chemical structures.

Mutagenicity Assay in Salmonella for Thirteen 2-Substituted-1H-phenanthro (9,10-d) Imidazoles

Abstract Some 2-substituted-1H-phenanthro [9,10-d] imidazole compounds synthesized as a predrugs were tested in mutagenicity assays in Salmonella strains TA97, TA98, and TA100 using a plate incorporation assay both with and without S9 mix. The 10 substances were mutagenic in TA97 and five of them were mutagenic only with metabolic activation, whereas one of them did not require the addition of S9. The eight substances were mutagenic in TA98 only with S9. For TA100, seven substances showed positive results both with and without S9, however another four required S9, whereas only one of them did not required metabolic activation. In summary, all of 13 substances derived from phenanthro [9,10-d] imidazole were found to be mutagenic for at least one or two of the three strains and their mutagenicity are discussed.

Genetic polymorphisms in preoperative myocardial infarction

Objective This study compared plasminogen activator inhibitor 1 and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in patients with myocardial infarction with ST-segment elevation before undergoing to coronary artery bypass grafting, and in patients who had previously undergone coronary artery bypass grafting. Method Seventy patients with myocardial infarction with ST-segment elevation, scheduled to undergo coronary artery bypass grafting, were included in the study group, and 70 patients who had previously undergone coronary artery bypass grafting were included in the control group. Genetic polymorphisms were determined using real-time polymerase chain reaction methods. Results Our data showed that there were no significant differences in plasminogen activator inhibitor 1 and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms or allele frequencies between the 2 groups. Conclusion Plasminogen activator inhibitor 1 and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms were not associated risk factors in patients who had myocardial infarction with ST-segment elevation and planned to have coronary artery bypass grafting.

Assessment of in vitro cytotoxic and genotoxic activities of some trimethoprim conjugates

Trimethoprim, a commonly used antibacterial agent, is widely applied in the treatment of variety of infections in human. A few studies have demonstrated an extensive exposure of man to antibiotics, but there is still a lack of data for cytotoxic effects including nephrotoxicity, gastrointestinal toxicity, hematotoxicity, neurotoxicity and ototoxicity. The main purpose behind this study was to determine cytotoxic and genotoxic activities of trimethoprim (1), trimethoprim with maleic acid (2) and trimethoprim in conjugation with oxalic acid dihydrate (3). The cytotoxic effects of these three conjugates were elucidated by employing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoium bromide (MTT) assay using embryonic rat fibroblast-like cell line (F2408) and H-ras oncogene activated embryonic rat fibroblast-like cancer cell line (5RP7). Additionally, determination of genotoxic activity of these three compounds were studied by using cytokinesis blocked micronucleus assay (CBMN) in human lymphocytes. The results demonstrated that trimethoprim alone and its combination with other compounds are able to induce both cytotoxic and genotoxic damage on cultured cells (F2408, 5RP7, human lymphocytes).

Investigation of genotoxic effects of paraben in cultured human lymphocytes

Abstract Paraben is a phenolic derivative of benzoic acid extensively used as preservatives in food, pharmaceutical, and cosmetic industries due to its antimicrobial characteristics. The objective of this study was to evaluate the in vitro genotoxic effects of paraben in human lymphocyte cultures. Cells were analyzed by cytokinesis-block micronucleus (CBMN), chromosome aberration (CA), sister chromatid exchange (SCE), and comet tests. For CBMN, CA, and SCE assays, the human lymphocytes were isolated from healthy donors and incubated with 500, 250, 100, and 50 µg/mL of paraben for 24 and 48 h, and for comet assay, cells were exposed to 1000, 750, 500, and 250 µg/mL of paraben for an hour. Results showed that numbers of MN and SCEs were not significant in the cells exposed to paraben when compared to the solvent control. However, 500 and 250 µg/mL of paraben induced the CA after 24 h. Also, we observed a significant decrease in the cytokinesis-block proliferation index in cells exposed 250–500 µg/mL paraben for 24 h, and 100, 250, and 500 µg/mL for 48 h. The mitotic index was also decreased at all concentrations and periods. However, the proliferation index was statistically decreased at all concentrations after 48 h treatments. Only the highest concentration of paraben caused DNA migration (mean tail length) in human lymphocytes analyzed by Comet assay. Taken together, results indicated that paraben had cytotoxic effects and caused genotoxicity by affecting directly chromosomes and DNA in human lymphocyte cells in vitro, and may have genotoxic potential for human.

In vitro genotoxic and cytotoxic effects of some paraben esters on human peripheral lymphocytes

Abstract Parabens (PBs) are p-hydroxybenzoic acid ester compounds commonly employed as antimicrobial preservatives, mainly in food, cosmetic, and pharmaceutical products. The aim of the present study was to investigate the genotoxic and cytotoxic effects of some paraben esters (butyl paraben, propyl paraben, isobutyl paraben, and isopropyl paraben) on human peripheral lymphocytes, using in vitro sister chromatid exchange (SCE), chromosome aberration (CA), and cytokinesis-block micronucleus (CBMN) tests. Lymphocyte cultures were treated with four concentrations of PBs (100, 50, 25 and 10 µg/mL) for 24 and 48 h. Paraben esters significantly induced MN formations as compared to solvent control. Furthermore, butyl paraben and propyl paraben increased MN formations a concentration-dependent manner at 24 and 48 h. PBs increased the CA at 24 and 48 h. However, this increase was not meaningful for butyl paraben and isopropyl paraben at 48 h when compared with solvent control. Butyl, isobutyl, and isopropyl paraben significantly increased the SCE at 24 and 48 h. However, propyl paraben did not induce SCE meaningfully in both treatment periods. A significant decrease in the cytokinesis-block proliferation index and mitotic index was observed in cells exposed to all concentrations of PBs at 24 and 48 h. However, proliferation index was not affected at all concentrations of PBs after 24 h treatment, although it was decreased at the highest concentration of PBs at 48 h. It is concluded that all of the paraben esters used in this study have highly genotoxic and cytotoxic effects on human lymphocytes cells in vitro.Parabens (PBs) are p-hydroxybenzoic acid ester compounds commonly employed as antimicrobial preservatives, mainly in food, cosmetic, and pharmaceutical products. The aim of the present study was to investigate the genotoxic and cytotoxic effects of some paraben esters (butyl paraben, propyl paraben, isobutyl paraben, and isopropyl paraben) on human peripheral lymphocytes, using in vitro sister chromatid exchange (SCE), chromosome aberration (CA), and cytokinesis-block micronucleus (CBMN) tests. Lymphocyte cultures were treated with four concentrations of PBs (100, 50, 25 and 10 µg/mL) for 24 and 48 h. Paraben esters significantly induced MN formations as compared to solvent control. Furthermore, butyl paraben and propyl paraben increased MN formations a concentration-dependent manner at 24 and 48 h. PBs increased the CA at 24 and 48 h. However, this increase was not meaningful for butyl paraben and isopropyl paraben at 48 h when compared with solvent control. Butyl, isobutyl, and isopropyl paraben significantly increased the SCE at 24 and 48 h. However, propyl paraben did not induce SCE meaningfully in both treatment periods. A significant decrease in the cytokinesis-block proliferation index and mitotic index was observed in cells exposed to all concentrations of PBs at 24 and 48 h. However, proliferation index was not affected at all concentrations of PBs after 24 h treatment, although it was decreased at the highest concentration of PBs at 48 h. It is concluded that all of the paraben esters used in this study have highly genotoxic and cytotoxic effects on human lymphocytes cells in vitro.

An in vitro investigation of genotoxic effects of dexketoprofen trometamol on healthy human lymphocytes

Abstract Non-steroidal anti-inflammatory drugs are drugs with analgesic, antipyretic, and anti-inflammatory effects. This study uses in vitro methods to investigate the potential and unknown genotoxic effects of dexketoprofen trometamol, an active substance in painkillers, on healthy human lymphocytes. In this study, a cytokinesis-block micronucleus cytome assay is used to investigate potential clastogenic, aneugenic activity and to identify chromosome breakages caused by the active drug substance dexketoprofen trometamol; a comet assay is performed to identify the genotoxic damage resulting from DNA single-strand breaks; a real-time reverse transcription polymerase chain reaction panel system is used to evaluate the potential negative effects on the expression of the genes responsible for DNA damage assessment. Dexketoprofen trometamol induces toxic effects in healthy human lymphocytes at concentrations of 750–1000 µg/mL and above, and shows clastogenic, aneugenic activity by inducing micronucleus formations at exposures of 750–500 µg/mL. At concentration intervals of 1000, 500, 250, 100 µg/mL, dexketoprofen trometamol also resulted in DNA damage in the form of strand breaks, as demonstrated by highly significant increases in DNA tail length and density comet parameters when compared to spontaneous values. Human lymphocytes exposed to 750–100 µg/mL dexketoprofen trometamol were found to have significantly increased levels of expression of the XPC, XRCC6, PNKP genes in the DNA damage signaling pathway. It can be concluded that dexketoprofen trometamol may have cytotoxic, cytostatic, genotoxic effects on healthy human lymphocytes in vitro, depending on the concentration and duration of exposure. It is anticipated that this outcome will be supported by advanced studies.