Ameliorative effect of certain antioxidants against mercury induced genotoxicity in peripheral blood lymphocytes

Various antioxidants play an important role in reducing the reactive oxygen species (ROS) by scavenging them directly or indirectly. Mercury (Hg) is one of the known hazardous genotoxicant, induces the genotoxicity by enhancing the ROS. In the present study, three structurally different bioactive compounds such as melatonin (0.2?mM), curcumin (3.87?µM) and andrographolide (0.4?µM) were evaluated against the genotoxic effect of mercury. All the experiments were conducted using the peripheral blood lymphocytes In Vitro. The cultures were exposed to different doses (2.63?µM; 6.57?µM; 10.52?µM) of mercury salt (HgCl₂) for studying various genotoxic indices. All three antioxidant compounds, alone and in combination with high dose of mercury, were added to the cultures with controls. For ascertaining genotoxicity, sister chromatid exchanges (SCEs), cell cycle proliferative index/replicative index (CCPI/RI), average generation time (AGT), population doubling time (PDT), %M1, %M2 and %M3 were assessed and analyzed using suitable statistical analysis. The results revealed a dose dependent increase in SCEs, AGT and PDT, with a concomitant reduction in CCPI values after treatment of mercury. Supplementation of these three antioxidant compounds effectively negated these genotoxic endpoints in treated cultures with improvement in the cell cycle kinetics i.e. CCPI. The antimutagenic activity of these compounds on mercury induced genotoxicity was in the following order: melatonin?>?curcumin?>?andrographolide. In conclusion, these compounds have ameliorated mercury induced increase in genotoxic indices due to their excellent antioxidant properties and the combination seems to be effective.     

Genotoxic effects in human lymphocytes exposed to arsenic and vitamin A.

Arsenic is a ubiquitous trace element and a well-established human carcinogen. In search for an 'antidote' to this global poison, this work was undertaken to study the probable beneficial effect of vitamin A upon arsenic induced genotoxicity. Peripheral blood lymphocyte culture was carried out to study the effects of arsenic at three different dose levels (0.5, 1 and 2 microg) for 24 h prior to harvesting. In addition, mutagenic in vitro effect of ethyl methanesulphonate was studied as a positive control. Genotoxic variables presented here are sister chromatid exchanges (SCE), cell cycle proliferative index/replicative index (CCPI/RI), average generation time (AGT) and population doubling time (PDT). Inevitably, arsenic treatment showed dose-dependent augmentation in the incidences of SCE and CCPI/RI together with AGT and PDT. However, vitamin A supplemented arsenic cultures demonstrated remarkable resurgence in the described genotoxic parameters. This data shows that vitamin A might be a useful interventional treatment in arsenic poisoning.     

Mitigative role of melatonin and α-tocopherol against mercury-induced genotoxicity

Abstract

The present study was conducted to elucidate the protective effect of melatonin (MLT) and α-tocopherol on mercury-induced genotoxicity in human blood cultures. The in vitro effects of inorganic mercury added to human lymphocytes on the cell-cycle proliferative index (CCPI)/proliferation replicative index (PRI) and sister chromatid exchange (SCE) using fluorescence plus Giemsa staining were examined. A significant increase occurred in SCE per metaphase (SCE/chromosome and SCE/cell) and inhibition of proliferative kinetics, which resulted in a decline of the replicative index, in comparison to the controls. Treated lymphocyte cultures also exhibited a reduction in %M1 and %M2 metaphase plates, but an increase in %M3 metaphase plates was noticed. Adding α-tocopherol and MLT individually and in combination indicated a mitigative effect by reducing the genotoxic potential of treated cultures. The percent amelioration for all the three parameters, namely, frequency of SCE, SCE/plate and SCE/chromosome as well as CCPI, was comparatively high with MLT and α-tocopherol in combination than MLT followed by α-tocopherol. The percent mitigation was better in combined antioxidant additions to toxicant-exposed cultures, compared to MLT, whereas the percent mitigation by α-tocopherol alone was less for average generation time and population doubling time, respectively.     

Investigation of cytotoxic and genotoxic effects of the antihistaminic drug,loratadine, on human lymphocytes

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.     

Argemone oil induces genotoxicity in mice

Context: Argemone mexicana L. is native to Mexico and the plant extracts are used in traditional medicine in India and South American countries. Argemone oil (AO) is a common adulterant of mustard oil in India and causes serious pathophysiological consequences leading to outbreaks of epidemic dropsy among consumers. In vivo cytogenetic studies on the toxicological effects of AO and its component alkaloids are limited. Objective: The present study was undertaken to evaluate the safety of AO by assessment of their in vivo genotoxic potential in bone marrow cells of mice. Materials and methods: AO mixed in corn oil in the proportions of 0.01, 0.1, and 1?ml AO/kg body weight in a total volume of 10?ml/kg body weight and a single undiluted dose of AO (10?ml/kg body weight) were administered intraperitoneally in separate groups of male Swiss Albino mice for 24?h. In addition, a single concentration of sanguinarine (SG) (50?mg/kg body weight) was also administered. Genotoxicity was evaluated by chromosome aberration (CA) and sister chromatid exchange (SCE) tests. Bromodeoxyuridine (BrdU) differential technique was used to study the effect on cell replication by the calculation of average generation time (AGT). Results: The minimum effective concentrations that produced significant frequencies of CA and SCE were 0.1 and 0.01?ml/kg, respectively. AO and SG induced an insignificant increase of AGT indicating that they are non-cytotoxic in the concentrations tested.

Discussion and conclusion: Our results confirm that AO is genotoxic even at low concentrations and its usage should be checked.     

Evaluation of DNA damage induced by norcantharidin in human cultured lymphocytes

Norcantharidin (NCTD) is currently used in the treatment of several cancers such as leukemia, melanoma and hepatoma. The mechanism of action of NCTD is suggested to involve induction of apoptosis of cancer cells via production of reactive oxygen species. In this study, the genotoxic effect of different concentrations of NCTD (1, 10 and 20?μm) in human lymphocytes was investigated using sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) assays. The results revealed that NCTD significantly increased the rate of SCEs (p?<?0.05) in a dose-dependent manner. In addition, NCTD significantly increased the number of high-frequency cells (SCEs?≥?8, p?<?0.05). However, NCTD did not have any significant effect on the rate of CAs (p?>?0.05). In addition, no significant differences were detected in the mitotic index or proliferative index at examined doses (up to 20?μm). In conclusion, NCTD is genotoxic to human cultured lymphocytes as measured by SCE assay.     

Investigation of genotoxic effects of paraben in cultured human lymphocytes

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 and in vivo effects of melatonin on sister chromatid exchange in human blood lymphocytes exposed to hypoxia

Objective: Many studies have shown that melatonin (MLT) has an anti-genotoxic effect in various tissues and cell lines. The aim of this study was to investigate the anti-genotoxic effect of MLT on normal human peripheral lymphocytes by assessing sister chromatid exchange (SCE) in vitro and in vivo. Materials and methods: Cells were treated with 50 and 200?μM of MLT. The human volunteers (n?=?20) for the in vivo study were administered a single dose of 3?mg MLT daily for 2 weeks. After sufficient time for its clearance, 1.5?mg of MLT daily was then administered to the same volunteers at same the period. Results: Our results demonstrated the anti-genotoxic effect of MLT in human blood lymphocyte in vitro and in vivo. In vitro, hypoxia increased the SCE frequency compared to the control and both doses of MLT significantly decreased the SCE frequency in the hypoxic cells (p?<?0.001). In vivo, oral administration of 3?mg MLT significantly increased the frequency of SCE, yet a small increase of SCE by hypoxia was found. Oral administration of 1.5?mg MLT showed no DNA damage but it had an anti-genotoxic effect. Discussion and conclusion: MLT may prove useful for reducing the genotoxic effects of hypoxia in peripheral lymphocytes and suggest its possible role for ischemic diseases.     

Vitamin E protects human lymphocytes from genotoxicity induced by oxaliplatin

Oxaliplatin is a platinum-based anticancer drug that has been shown to be genotoxic to the normal cells. Vitamin E is a potent antioxidant that may protect and enhance the repair of the damaged DNA. In this study, we aimed to evaluate the genotoxic effect of oxaliplatin on DNA by measuring the frequency of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) in cultured human lymphocytes. We also attempted to explore the potential protective effect of vitamin E on chromosomal damage induced by oxaliplatin. Results showed that oxaliplatin significantly increased the frequency of CAs (p?<?0.001) and SCEs (p?<?0.001) as compared to control. This chromosomal damage, caused by oxaliplatin, was significantly decreased by pretreatment of cells with vitamin E. Moreover, the results showed that oxaliplatin caused a significant reduction in the cell kinetic parameters, the mitotic index (MI) and the proliferative index (PI). However, vitamin E did not affect this reduction in the MI and PI. Therefore, we conclude that oxaliplatin is genotoxic, and vitamin E can prevent the chromosomal damage induced by oxaliplatin but it has no effect on oxaliplatin-induced cytotoxicity.     

Ziprasidone induces cytotoxicity and genotoxicity in human peripheral lymphocytes

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?μg/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.     

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.     

Gossypol decreases tumor necrosis factor-α-induced intercellular adhesion molecule-1 expression via suppression of NF-κB activity

Gossypol is a yellowish polyphenolic compound originally from cotton plant, which has been shown to exert a potential for anti-cancer and anti-inflammatory effects. However, its molecular mechanism is not thoroughly understood on breast cancer cells known to highly express intercellular adhesion molecule-1 (ICAM-1) for their adhesion and metastasis. This study aims to investigate the effect of gossypol on tumor necrosis factor (TNF)-α-stimulated ICAM-1 via nuclear factor-kappa B (NF-κB) activity. Gossypol was shown to inhibit TNF-α-induced ICAM-1 expression and U937 cell adhesion to MDA-MB-231 and MCF-7 cells. Additionally, TNF-α-induced MDA-MB-231 cell invasion was blocked in the presence of gossypol. Chromatin immunoprecipitation analysis demonstrated that gossypol blocks NF-κB binding on the ICAM-1 promoter regions. Additionally, TNF-α-induced NF-κB activation was completely suppressed in the presence of gossypol. Gossypol did not directly suppress the binding of NF-κB to the DNA but rather inhibited the nuclear translocation of p65 and p50 via phosphorylation and degradation of IκB. We also found that gossypol suppresses NF-κB activation induced by a wide variety of agents, including taxol, okadaic acid, and phorbol myristate acetate. Taken together, gossypol effectively inhibited TNF-α-induced ICAM-1 expression via the suppression of NF-κB activation and in vitro adhesion and invasion in human breast cancer cells.     

Examination of Gossypol-Pluronic Micelles as Potential Radiosensitizers

Chemoradiotherapy, the combination of chemotherapy and radiotherapy to treat cancer, has the potential to enhance local therapeutic effects and simultaneously treat systemic disease. However, chemoradiotherapy may also enhance normal tissue effects leading to both acute and late toxicities. Furthermore, subtherapeutic chemoradiotherapy may result in aggressive tumor repopulation. Tumor-specific radiosensitizing chemotherapy may yield a synergistic therapeutic effect and avoid augmentation of normal tissue toxicity. In this study, the radiosensitizing effects of gossypol were investigated. Also, Pluronics were studied for gossypol solubilization and co-radiosensitization effects. Gossypol inhibits Bcl-2 and Bcl-X_L, antiapoptotic proteins that are overexpressed in various cancer cells. Pluronic micelles (P85, F88, L35, and P123) effectively encapsulated gossypol, raising its water solubility by more than 1000-fold. Cytotoxic, anticlonogenic, and radiosensitizing effects were evaluated to characterize gossypol and Pluronic combinations. Gossypol and P85 had the strongest antiproliferative effect on A549 human lung adenocarcinoma cells in a cell viability assay. The IC₅₀ value was seven times lower than gossypol only treatment (330 ± 70 nM vs 2400 ± 400 nM, (mean ± SE)). Gossypol and P85 showed significant inhibition of clonogenic survival, approximately 30% inhibition, compared to treatment with gossypol alone. An experimental sequencing study demonstrated greater inhibition of clonogenic survival when drug treatment followed radiation compared to a sequence of drug treatment followed by radiation. These results suggest that Pluronic micelles readily solubilize gossypol and that the combination of gossypol and P85 may augment the therapeutic effects of ionizing radiation.KEY WORDS: chemoradiotherapy, gossypol, Pluronic, polymeric micelles, radiosensitization     

AN IN VITRO STUDY OF INHIBITORY ACTIVITY OF GOSSYPOL, A COTTONSEED EXTRACT, IN HUMAN CARCINOMA CELL LINES

Gossypol, a cottonseed extract, has been shown to have antiproliferative activity in a variety of cancer cell lines. The objective of this study was to determine the inhibitory effects of gossypol on cell proliferation. Five human carcinoma cell lines were evaluated including endometrial (RL95-2), ovarian (SKOV-3), medullary thyroid (TT), and adrenocortical (NCI-H295R and SW-13). Gossypol and the metabolite, apogossypol hexaacetate, were examined at concentrations up to 500 μg ml⁻¹ and the IC₅₀ was determined using the MTT assay. Gossypol and apogossypol hexaacetate produced a dose-dependent growth inhibition in all cellular lines examined. The IC₅₀ for gossypol ranged from 1.3 to 18.9 μM while the IC₅₀ for apogossypol hexaacetate ranged from 5.2 to 9.0 μM. The results indicate that gossypol possesses antiproliferative action toward human carcinoma cells in vitro. These investigations suggest that gossypol may have therapeutic potential for the treatment of cancer.     

Oxcarbazepine-induced cytotoxicity and genotoxicity in human lymphocyte cultures with or without metabolic activation

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.     

Amelioration of melatonin on oxidative stress and genotoxic effects induced by cisplatin in vitro

In this study, we made an effort to evaluate the possible protective actions of melatonin on cisplatin-induced oxidative damage in mice brain homogenate and genotoxic effects in human lymphocytes under in vitro conditions. The tissue homogenate was divided into three parts. The first portion was kept as control treated with dimethyl sulphoxide (DMSO) (group 1) while the second and third portion were treated with 24 µg/g tissue cisplatin alone (group 2) and 24 µg/g tissue cisplatin in combination with 3?mM melatonin (group 3), respectively. We measured the oxidative stress biomarkers such as lipid peroxidation, 8-hydroxy 2′ deoxyguanosine (8-OHdG) and antioxidant parameters such as reduced glutathione, superoxide dismutase, glutathione peroxidase, and glutathione reductase in brain homogenate. Likewise peripheral venous blood was collected from healthy donors and human lymphocyte culture was done using karyotyping medium. Cultures were divided into three groups. Group 1 was the control i.e. lymphocytes treated with DMSO 5 µg/mL. In group 2, lymphocytes were treated with 2 µg/mL cisplatin and group 3 with a combination of 2 µg/mL cisplatin and 0.3?mM melatonin. Incubation of tissue homogenates with cisplatin elevated the malondialdehyde and 8-OHdG levels which were then reversed by melatonin. Reduction in antioxidant parameters with respect to corresponding controls were also restored by melatonin treatment. Furthermore, supplementation of melatonin was found to modulate the chromosome damage elicited by cisplatin which was determined using Giemsa (GTG) banding and karyotyping. These findings suggest that melatonin improves the cellular function and helps them to survive in the belligerent environment created by free radicals.     

Assessment of genotoxicity of pyrethrin in cultured human lymphocytes

Pyrethrin is an insecticide that is obtained from the Chrysanthemum flower (Pyrethrum). In this study, we examined the genotoxic effects of pyrethrin on cultured human lymphocytes using sister chromatid exchanges (SCEs) and 8-hydroxy deoxyguanosine (8-OHdG) assays. Cultures were treated with different concentrations of pyrethrin (25, 50, and 100?μg/mL), which was dissolved in in dimethyl sulfoxide (DMSO). The results showed that treatment of cultured lymphocytes with pyrethrin at 50?μg/mL and 100?μg/mL induced significant elevation in SCEs (p?p?p?相似文献   

Evaluation of genotoxic and antigenotoxic effects of boron by the somatic mutation and recombination test (SMART) on Drosophila

Objective: In this study, different concentrations of boron have been evaluated for genotoxic and antigenotoxic properties by using the somatic mutation and recombination test (SMART) on Drosophila melanogaster. Study Design: The treatment concentrations were chosen to a pretest. Third-instar larvae trans-heterozygous for two genetic markers, multiple wing hair (mwh) and flare (flr3), were treated at different concentrations (0.1, 5, 10, 20, and 40?mg/mL) of boron. In addition to investigating antigenotoxic effects, the same boron concentrations were co-administered with 0.1?mM Ethyl Methane Sulfonate (EMS). Distilled water was used as a negative control; 0.1?mM of EMS was used as a positive control. For the chronic feeding study, small plastic vials were prepared with 1.5?g of dry Drosophila Instant Medium and 5?mL of the respective test solution. Hundreds of trans-heterozygous larvae were embedded into this medium. Feeding ended with pupation of the surviving larvae. After metamorphosis, all surviving flies were collected and stored in a 70% ethanol solution. Preparation and microscopic analyses of wing were made after the treatment. Then the observed mutations were classified according to size and type of mutation per wing. Results: Results indicated that there is no significant genotoxic effect with all of the boron concentrations. In addition, the antigenotoxic activities of boron against EMS were tested. Results indicated that all boron concentrations (0.1, 5, 10, 20 and 40?mg/mL) were able to abolish the genotoxic effects induced by the EMS. Conclusion: It is suggested that the observed effects can be linked to the antioxidant properties of boron. Moreover, these in vivo results will contribute to the antigenotoxicity database of boron.     

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

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.     

Nitroimidazole derivatives: non-randomness sister chromatid exchanges in human peripheral blood lymphocytes

Nitroimidazole derivatives exhibited genotoxic effect in different experimental conditions. This study focuses on an evaluation of possible genomic targets, at a chromosomal level, of two 5-nitroimidazoles (ornidazole and metronidazole) using the in vitro human peripheral blood culture as experimental system. We observed that both derivatives showed a decrease in mitotic index (MI) (P < 0.001), an increase in sister chromatid exchanges (SCE) frequency (P < 0.001) and no modifications in cellular proliferation kinetics (CPK). As a null hypothesis we considered the assumption that larger chromosomes should harbor more SCE, which was viewed using a novel sequential G-band (400 band resolution)/SCE technique. The analysis showed highly significant chi square values (P < 0.001), indicating that SCE frequency per chromosome is not proportional to chromosome length. SCE could be considered an instability indicator due to the high correlation between SCEs in certain chromosomal bands and the exposure to nitroimidazole derivatives. Copyright © 2008 John Wiley & Sons, Ltd.