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1.
Context: Loratadine (LOR) is a new generation antihistamine used in the treatment of allergic disorders. Objective: The aim of this study was to evaluate the cytogenotoxic effect of LOR on human peripheral blood lymphocytes. Materials and methods: 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. Results: 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. Discussion: Although most of previously findings have shown that LOR does not reflect genotoxicity, our results indicated that it may be a genotoxic drug. Conclusion: 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.  相似文献   

2.
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.  相似文献   

3.
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.  相似文献   

4.
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.  相似文献   

5.
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.  相似文献   

6.
There has been considerable debate about the relationship between epilepsy and cancer. Oxcarbazepine (OXC) is used for treating certain types of seizures in patients with epilepsy. There have been no detailed investigations about genotoxicity of OXC and its metabolites. Therefore, the aim of this study is to investigate the cytotoxic and genotoxic effects of OXC and its metabolites on cultured human lymphocytes. The cytotoxicity and genotoxicity of OXC on human peripheral blood lymphocytes were examined in vitro by sister chromatid exchange (SCE), chromosomal aberration (CA) and micronucleus (MN) tests. Cultures were treated with 125, 250 and 500?μg/ml of OXC in the presence (3?h treatment) and absence (24?h and 48?h treatment) of a metabolic activator (S9 mix). Dimethyl sulfoxide (DMSO) was used as a solvent control. OXC showed cytotoxic activities due to significant decreases in mitotic index (MI), proliferation index (PI) and nuclear division index (NDI) in the absence of S9 mix when compared with solvent control. Metabolites of OXC also significantly reduced MI and PI in cultures with S9 mix. OXC significantly increased the CAs, aberrant cells, SCE and MN values in the presence and absence of S9 mix. Our results indicated that both OXC and its metabolites have cytotoxic, cytostatic and genotoxic potential on human peripheral blood lymphocyte cultures under the experimental conditions. Further studies are necessary to elucidate the relationship between cytotoxic, cytostatic and genotoxic effects, and to make a possible risk assessment in patients receiving therapy with this drug.  相似文献   

7.
Abstract

The aim of this study was to investigate the genotoxic and antigenotoxic effects of Salvia fruticosa (Sf) leaf extract with the absence and presence of S9 mix using sister chromatid exchange (SCE), chromosome aberration (CA) and micronucleus (MN) formation test systems in human peripheral blood lymphocytes (HPBLs) that were treated with 1.5-, 3.0- and 6.0-µL/mL concentrations for 24- and 48-hour treatment periods. The cytotoxicity of Sf leaf extract was also investigated by calculating the mitotic index (MI), proliferation index (PI) and nuclear division index (NDI). In the absence of S9 mix, Sf leaf extract alone increased SCE frequency at the 48-hour treatment period; however, it induced the CA and MN at all concentrations and at all treatment periods. Sf plus MMC (mitomycin C) synergically induced SCE and CA, except the highest concentration of Sf leaf extract and MMC on induction of SCE. In addition, Sf leaf extract induced the effect of MMC on MN frequency for 24 hours, but it significantly decreased the effect of MMC on MN frequency for the 48-hour treatment period. Sf leaf extract showed a cytotoxic effect by decreasing the MI; however, it did not decrease the PI and NDI. In the presence of S9 mix, Sf leaf extract did not increase the SCE, when compared to solvent control, whereas it reduced the effect of cyclophosphamide (Cyp). Sf leaf extract induced the CA and MN, but could not increase the effect of Cyp on CA and MN formation. Sf leaf extract had no cytotoxic effect; however, it induced the cytotoxicity of Cyp.  相似文献   

8.
Macrolide antibiotic roxithromycin was evaluated in terms of its genotoxic, cytotoxic and oxidative stress effects. For this purpose; 25, 50, 100 and 200?μg/mL concentrations of roxithromycin were dissolved in dimethyl sulfoxide and treated to human peripheral blood lymphocytes for two different treatment periods (24 and 48?h). In chromosome aberration (CA) and micronucleus (MN) tests, roxithromycin did not show genotoxic effect. But it induced sister chromatid exchange (SCE) at the highest concentration (200?μg/mL) for the 24-h treatment period and at all concentrations (except 25?μg/mL) for the 48-h treatment period. Looking at cytotoxic effect of roxithromycin, statistically insignificant decreases on mitotic index and proliferation index were observed. Roxithromycin decreased nuclear division index (NDI) at highest two concentrations (100 and 200?μg/mL) for the 24-h treatment period and at all concentrations (expect 25?μg/mL) for the 48-h treatment period. Total oxidant values, total antioxidant values and oxidative stress index did not change with roxithromycin treatment. Eventually, roxithromycin did not have genotoxic and oxidative stress effects in human-cultured lymphocytes.  相似文献   

9.
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.  相似文献   

10.
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.  相似文献   

11.
The aim of this study was to evaluate the potential cytotoxic effects of Benodanil fungicide by employing both mitotic index (MI) and mitotic phases on the root meristem cells of Allium cepa and genotoxic effects by using in vitro micronucleus assay (MN) in human peripheral blood lymphocyte. In the Allium root growth inhibition test, the EC50 value was first determined as 25?ppm. Then, 2?×?EC50 value (50?ppm), EC50 value (25?ppm), and 1/2?×?EC50 value (12.5?ppm) were tested with different treatment periods (24, 48, and 72?h). Both negative and positive controls were also used in parallel experiments. We obtained that mitotic index and prophase index decreased when compared with the control in all concentrations. In the micronucleus assay, lymphocytes were treated with various concentrations (250, 500, 750, and 1000?µg/ml) of Benodanil for 24 and 48?h. The results showed that Benodanil did not induce MN frequency in all concentrations of both treatment periods. Additionally, it was determined that this pesticide decreased nuclear division index (NDI) significantly. It was concluded that Benodanil has a cytotoxic effects depending on decreasing of MI and NDI.  相似文献   

12.
The effects of the low-calorie artifical sweetener maltitol (E965), a sugar alcohol (Polyol), on sister chromatid exchange (SCE), chromosome aberration (CA), and micronucleus formation (MN) were investigated in human peripheral lymphocytes. Maltitol did not induce SCE at all concentrations (1.25, 2.5, and 5 mg/mL) and treatment periods (24 and 48 h). Maltitol induced CA, although not statistically significantly. Maltitol induced the frequency of MN at 24 and 48 h in a non-dose-dependent manner. In addition, maltitol did not decrease the replication index (RI) and the mitotic index (MI) at all concentrations and treatment periods. Maltitol did not alter the pH and osmolality of the medium. In conclusion, it can be concluded that maltitol has a weak genotoxic potential and it appears non-cytotoxic to human peripheral lymphocytes in vitro.  相似文献   

13.
The effects of the low-calorie artifical sweetener maltitol (E965), a sugar alcohol (Polyol), on sister chromatid exchange (SCE), chromosome aberration (CA), and micronucleus formation (MN) were investigated in human peripheral lymphocytes. Maltitol did not induce SCE at all concentrations (1.25, 2.5, and 5 mg/mL) and treatment periods (24 and 48 h). Maltitol induced CA, although not statistically significantly. Maltitol induced the frequency of MN at 24 and 48 h in a non-dose-dependent manner. In addition, maltitol did not decrease the replication index (RI) and the mitotic index (MI) at all concentrations and treatment periods. Maltitol did not alter the pH and osmolality of the medium. In conclusion, it can be concluded that maltitol has a weak genotoxic potential and it appears non-cytotoxic to human peripheral lymphocytes in vitro.  相似文献   

14.
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.  相似文献   

15.
Flurbiprofen is non-steroidal anti-inflammatory drug which is commonly used for its analgesic, antipyretic, and anti-inflammatory effects. The purpose of the study was to explore the genotoxic and cytotoxic effects of flurbiprofen in human cultured lymphocytes by sister chromatid exchange, chromosome aberration, and cytokinesis-blocked micronucleus tests. 10, 20, 30, and 40?μg/mL concentrations of flurbiprofen (solvent is DMSO) were used to treatment of human cultured lymphocytes at two different treatment periods (24 and 48 h). Flurbiprofen had no significant genotoxic effect in any of these tests. But exposing to flurbiprofen for 24 and 48 h led to significant decrease on proliferation index, mitotic index, and nuclear division index (NDI). Also, all decreases were concentration-dependent (except NDI at 24 h treatment period). Consequently, the findings of this research showed that flurbiprofen had cytotoxic effects in human blood lymphocytes.  相似文献   

16.
Potential mutagenic and genotoxic effects of Chlorthiophos, an organophosphate pesticide, were evaluated using four standard assays. Five different concentrations of the pesticide were tested by an Ames test using Salmonella typhimurium strains TA97, TA98, TA100, and TA102, with and without S9 metabolic activation. No concentrations of Chlorthiophos showed mutagenic activity on the TA97, TA100, and TA102 strains, with and without S9 fraction, but were all mutagenic to the TA98 strain without S9. Sister chromatid exchange (SCE), chromosome aberration (CA), and micronucleus (MN) tests were used to investigate the genotoxic effects of Chlorthiophos in human peripheral lymphocytes treated with 25, 50, 100, and 200 µg/mL concentrations of Chlorthiophos for 24 and 48 h. The nuclear division index (NDI), replication index (RI), and mitotic index (MI) were also calculated to determine the cytotoxicity of Chlorthiophos. No increase in SCE frequency was seen for any treatment period or concentration, but Chlorthiophos at 200 µg/mL increased the frequency of CAs. Increases in MN formation were only observed at Chlorthiophos concentrations of 200 µg/mL following 24 and 48 h treatments. Chlorthiophos treatment reduced the MI and NDI significantly, but had no effect on the RI. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 937–945, 2015.  相似文献   

17.
In this study, the genotoxic effects of sodium benzoate (SB) and potassium benzoate (PB) were investigated in cultured human peripheral lymphocytes using chromosomal aberrations (CA), sister chromatid exchange (SCE), and micronuclei (MN). The level of nuclear DNA damage of SB and PB were also evaluated using the comet assay. The lymphocytes were incubated with different concentrations of SB (6.25, 12.5, 25, 50, and 100 μg/ml) and PB (62.5, 125, 250, 500, and 1000 μg/ml). A significant increase was observed in CA, SCE, and MN, in almost all treatments compared to negative controls. SB and PB significantly decreased the mitotic index (MI) in all the treatments, compared to the negative controls. However, neither of the additives affected the replication index (RI). Although SB significantly increased DNA damage, PB did not cause a significant increase in DNA damage. The present results indicate that SB and PB are clastogenic, mutagenic and cytotoxic to human lymphocytes in vitro.  相似文献   

18.
The color additive, tartrazine (TRZ), is widely used in food products, drugs and cosmetics. Genotoxicity of TRZ and its metabolites has not been investigated in detail in the presence and absence of a metabolic activator (S9 mix) in human. Therefore, the aim of this study is to investigate the cytotoxic and genotoxic effects of TRZ and its metabolites on cultured human lymphocytes by using chromosome aberration (CA) and micronucleus (MN) tests. Cultures were treated with 625, 1250 and 2500?μg/ml of TRZ in the presence and absence of S9 mix. TRZ showed cytotoxic activity at the highest concentration due to significant decrease in mitotic index (MI) in the absence of S9 mix when compared with solvent control. TRZ and metabolites significantly increased the CAs and aberrant cells in the presence and absence of S9 mix at the higher concentrations. Increased MN values in cultures with and without S9 mix were found to significantly at the highest concentration when tested. Our results indicated that while both TRZ and its metabolites have genotoxic potential on human lymphocyte cultures with and without S9 mix, TRZ can induce cytotoxicity at the highest concentration in culture without S9 mix under the experimental conditions.  相似文献   

19.
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.  相似文献   

20.
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 microg/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).  相似文献   

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