Assessment of imidacloprid-induced mutagenic effects in somatic cells of Swiss albino male mice

Pesticides are being used for plant protection to increase food protection and to reduce insect-borne diseases worldwide. Exposure to the pesticides may cause genotoxic effects on both the target and nontarget organisms, including man. Therefore, the mutagenicity evaluation of such pesticides has become a priority area of research. Imidacloprid (IMI), a neonicotinoid insecticide, is widely used in agriculture either alone or in combination with other insecticides. A combined approach employing micronucleus test (MNT) and chromosomal aberrations assay (CA) was utilized to assess the mutagenicity of imidacloprid in bone marrow of Swiss albino male mice. IMI suspension was prepared in 3% gum acacia and administered at doses of 5.5, 11 and 22 mg/kg body weight for 7, 14 and 28 days to mice. IMI treatment resulted in a dose and time-dependant increase in the frequencies of micronuclei per cell and chromosomal aberrations in bone marrow cells. A statistically significant increase in chromosomal aberrations and micronuclei/cell was found only after daily treatment of IMI at highest selected dose (22 mg/kg body weight) for longest selected time period (28 days) compared to the control group. Thus, daily exposure of imidacloprid at a dose level of 22 mg/kg body weight for 28 days caused mutagenic effects on the somatic cells of Swiss albino male mice.     

Zoledronic acid induces cytogenetic toxicity in male germline cells of Swiss albino mice

This study mainly focuses on the cytogenetic toxicity induction by zoledronic acid (ZA), a nitrogen containing bisphosphonate (N-BPs) in the male germline cells of Swiss albino mice. A single intraperitoneal exposure with three different doses of ZA (2, 4, and 8?mg/kg body weight), toxicity was assessed by analyzing spermatogonial metaphase chromosome aberrations at 24?h, aberrant primary spermatocytes at week 4, and abnormal spermatozoa at week 8 posttreatment. Cyclophosphamide (40?mg/kg) and 0.9% NaCl were used as positive and vehicle controls respectively in the study. The results showed that there was a significant induction in the number of chromosomal aberrations especially at two doses of ZA (4 and 8?mg/kg) after 24?h in the spermatogonial cells (p?<?0.001) compared to vehicle control. The transmission genetic damages were noticed as aberrant spermatocytes with atypical bivalents (X-Y/autosomal asynapsis) at 4?mg/kg of ZA (p?<?0.01) and at 8?mg/kg of ZA (p?<?0.001) at week 4 posttreatment. A statistically significant higher number of abnormal spermatozoa (sperm) were also noticed at week 8 posttreatment of both at 4 and 8?mg/kg of ZA (p?<?0.001). Hence, from these genotoxicity studies, it can be concluded that ZA is genotoxic in male germline cells and has the potential of transmitting the genotoxic effects from spermatogonial cells to sperm in male Swiss mice.     

Assessment of chromosomal aberration in the bone marrow cells of Swiss Albino mice treated by 4-methylimidazole

4-Methylimidazole (4-MEI) is formed during the production of certain caramel coloring agents used in many food and drink products. It may also be formed during the cooking, roasting, or other processing of some foods and beverages. So it was unintentionally consumed in worldwide. This study was aimed to investigate the genotoxic and cytotoxic effects of 4-MEI using chromosome aberration (CA) and mitotic index (MI) in Swiss Albino mice. In this research, CA and MI of the mouse bone marrow cells were analyzed after treating the animals with 4-MEI (100, 130 and 160 mg/kg) for 12 h and 24 h treatment times. All data were analyzed using statistical methods. 4-MEI significantly increased the percentage of CAs at all concentrations for 12 h and at highest concentration for 24 h treatment periods. 4-MEI at highest concentration for 12 h and at all concentrations for 24 h decreased the MI in comparison with control. Genotoxic and cytotoxic effects of 4-MEI at 24 h treatment periods were concentration dependent. Consequently, it can be said that 4-MEI have genotoxic and cytotoxic effect in mouse.     

Antimutagenic and anticlastogenic effects of Turkish Black Tea on TA98 and TA100 strains of Salmonella typhimurium (in vitro) and mice (in vivo)

Context: Black tea has been reported to have significant antimutagenic and anticarcinogenic properties associated with its polyphenols theaflavins (TF) and thearubigins (TR). Similarly, Turkish black tea (TBT) also contains a considerable amount of TF and TR.

Objective: This study investigated the mutagenic, antimutagenic and anticlastogenic properties of TBT.

Materials and methods: The mutagenic and antimutagenic effects of TBT (10 to 40000?μg/plate) were investigated in vitro on Salmonella strains TA98 and TA100 with and without S9 fraction. Anticlastogenic effect was studied at concentrations of 300–1200?mg/kg TBT extract by chromosomal aberrations (CA) assay from bone marrow of mice.

Results: The results of this study did not reveal any mutagenic properties of TBT. On the contrary, TBT extract exhibited antimutagenic activity at >1000?μg/plate concentrations in TA98 strain with and without S9 activation (40% inhibition with S9 and 27% without S9). In TA100 strain, the antimutagenic activity was observed at?>20,000?μg/plate TBT extracts without S9 activation (28% inhibition) and at >1000?μg/plate with S9 activation (59% inhibition). A significant decrease in the percentage of aberrant cells (12.33%?±?1.27) was observed in dimethylbenz(a)anthracene (DMBA) plus highest concentration (1200?mg/kg) of TBT extract-treated group when compared to only DMBA-treated group (17.00%?±?2.28).

Discussion and conclusion: Results indicated that TBT can be considered as genotoxically safe, because it did not exert any mutagenic and clastogenic effects. As a result, TBT exhibited antimutagenic effects more apparently after metabolic activation in bacterial test system and had an anticlastogenic effect in mice.     

Evaluation of in vivo cytogenetic toxicity of europium hydroxide nanorods (EHNs) in male and female Swiss albino mice

Our group already demonstrated that europium hydroxide nanorods (EHNs) show none or mild toxicity in C57BL/6 mice even at high dose and exhibited excellent pro-angiogenic activity towards in vitro and in vivo models. In the present study, we evaluated the in vivo cytogenetic toxicity of intraperitoneally administered EHNs (12.5–250?mg/kg/b.w.) in male and female Swiss albino mice by analyzing chromosomal aberrations (CAs), mitotic index (MI), micronucleus (MN) from bone marrow and peripheral blood. Furthermore, we performed the cytogenetic toxicity study of EHNs towards Chinese hamster ovary (CHO) cells, in order to compare with the in vivo results. The results of CA assay of mice treated with EHNs (12.5–125?mg/kg/b.w.) showed no significant change in the formation of aberrant metaphases compared to the control group. Also, there was no significant difference in the number of dividing cells between the control group and EHNs-treated groups observed by MI study, suggesting the non-cytotoxicity of EHNs. Additionally, FACS study revealed that EHNs do not arrest cells at any phase of cell cycle in the mouse model. Furthermore, MN test of both bone marrow and peripheral blood showed no significant differences in the induction of MNs when compared with the control group. In vitro results from CHO cells also support our in vivo observations. Considering the role of angiogenesis by EHNs and the absence of its genotoxicity in mouse model, we strongly believe the future application of EHNs in treating various diseases, where angiogenesis plays an important role such as cardiovascular diseases, ischemic diseases and wound healing.     

In vivo assessment of genotoxic potential of brown shammah (smokeless tobacco) in bone marrow cells of mice

This study was aimed to assess the genotoxicity of brown shammah (BS), a local form of smokeless tobacco, popular in Middle East countries including Yemen, Saudi Arabia and Sudan. The genotoxicity was explored using in vivo chromosomal aberration (CA), micronucleus (MN) and sperm abnormality (SA) assays. In addition, oxidative stress was also determined using various hepatic markers. Swiss albino mice were selected for the study, which were divided in to 5 groups of six animals each. They include, negative control (NC, received only vehicle) as well as positive control group (PC, received vehicle for 2 weeks followed by administration of cyclophosphamide, CP). Depending upon their dose, three BS treated animal groups were BS-100, 300 and 900 mg/kg. Doses of BS were obtained by suspending BS in 0.5% CMC (carboxy methyl cellulose) and orally administered once a day for 2 weeks. Significant augmentation of the average percentage of aberrant metaphase (AM), CA per cells and suppressed mitotic activity was observed on post administration of BS. In addition, BS increased the occurrence of MNPCEs (micronucleated polychromatic erythrocytes) formation, induced cytotoxicity and increased percentage of abnormal sperms as compared to NC. Moreover, BS also induced oxidative stress as the activities of hepatic superoxide dismutase (SOD) and glutathione (GSH) were reduced and malondialdehyde (MDA) content were increased by BS. Cyclophosphamide was utilized as clastogen, showed anticipated positive results and confirmed the sensitivity of test system. Therefore, it may be deduced from the study that the BS possesses genotoxic effects on mice bone marrow and germ cells in vivo.     

Evaluation of protective efficacy of Spirulina fusiformis against mercury induced nephrotoxicity in Swiss albino mice.

The toxicity of mercury to animals and man is well established and this depends greatly on the form of the mercury compounds. In most animals' species, including man, the kidney is the main site of deposition of inorganic mercury and target organ for its toxicity. In the present study Spirulina fusiformis (a cyanobacterium, belongs to family--Oscillatoriaceae) has been investigated as a possible modifier of mercury induced renal damages in Swiss albino mice. Animals were divided into four groups. (i) Control group--only vehicle (0.9% NaCl) was administered as i.p. (ii) HgCl(2) treated group--5.0 mg/kg b.wt. HgCl(2) was administered as i.p. (iii) Spirulina treated group--800 mg/kg b.wt. Spirulina extract was administered orally. (iv) Combination group--S. fusiformis was administered 10 days before mercuric chloride administration and continued upto 30 days after mercuric chloride administration (5.0 mg/kg b.wt.). The animals were autopsied on 1, 3, 7, 15 and 30 days after treatment and the activity of alkaline phosphatase (ALP), acid phosphatase (ACP), lactate dehydrogenase (LDH) and MDA (malondialdehyde) level were measured in kidney homogenates. The results indicated that there was a time-dependent significant enhancement in MDA content and ACP activity and decrease in LDH and ALP activity observed after HgCl(2) treatment. Mercury intoxication also induces pathological alterations in the kidney such as degeneration of glomerulus, proximal and distal tubules. A dose-dependent mortality was also observed following administration of different doses of HgCl(2). In combined treatment of Spirulina with HgCl(2), a significant decrease in MDA content and ACP activity and elevation in LDH and ALP activity was observed as compared to HgCl(2) treated group. Spirulina pre- and post-treatment with mercury also significantly reduces pathological alterations in kidney. Thus, the results from the present study suggest that S. fusiformis can significantly modify the renal damages against mercuric chloride induced toxicity.     

Cytogenetic risk assessment of etoposide from mouse bone marrow

Increased clinical applications of the anticancer drug etoposide (a non-intercalative epipodophyllotoxin derivative) and the frequent induction of a second malignancy, particularly leukaemia, in post-etoposide-treated cancer survivors warrant detailed genotoxicity testing of etoposide. The genotoxicity test results available on etoposide are either primarily in in vitro test systems or in lower organisms after treatment with unusually high doses, or after chronic exposures, having little extrapolative value to humans. Therefore, a cytogenetic risk assessment study on etoposide in mouse in vivo was undertaken after a low dose (in accordance with the human therapeutic dose) single exposure. The cytogenetic toxicity of etoposide was assessed from bone marrow of mouse at three separate endpoints: chromosomal aberration and mitotic index studies at 24 h post-treatment and the micronucleus test (MNT) at 30 h post-treatment. The flame drying technique using colchicine, hypotonic sodium citrate, methanol-glacial acetic acid and Giemsa was followed for the preparation of slides for the metaphase chromosomal aberration and mitotic index studies and a simple technique was followed for the MNT. Although induction of chromosomal aberrations, excluding gaps, per 100 metaphases by 10 and 15 mg kg(-1) etoposide was not significant statistically, 20 mg kg(-1) of etoposide induced a significantly higher number of chromosomal aberrations in female (P < or = 0.01) and male (P < or = 0.05) mice. There was no significant change in the induced percentages of dividing cells by any of the doses of etoposide tested. The micronucleus induction also was not significant statistically with the lowest dose but it was significant in female (P 相似文献   

Comparative study of the clastogenicity of functionalized and nonfunctionalized multiwalled carbon nanotubes in bone marrow cells of Swiss‐Webster mice

The development of nanotechnologies may lead to environmental release of nanomaterials that are potentially harmful to human health. Among the nanomaterials, multiwalled carbon nanotubes (MWCNTs) are already commercialized in various products which can be in direct contact with populations. However, few studies address their potential toxicity. Although a few reports on the cytotoxicity of carbon nanotubes (CNTs) have been published, very little is known about their toxicity or genotoxicity in mammalian cells. We have for the first time compared the clastogenic/genotoxic potential of functionalized and nonfunctionalized MWCNTs in bone marrow cells of Swiss‐Webster mice; using mitotic index (MI), chromosome aberrations (CA), micronuclei (MN) formation, and DNA damage in leukocytes as toxicologic endpoints. Six groups of five male mice, each weighing ～30 ± 2 g, were administered intraperitoneally, once a day for five days with doses of 0.25, 0.5, 0.75, mg/kg body weight (BW) of functionalized and nonfunctionalized MWCNTs. Four vehicle control groups (negative) and a positive control group (carbon black) were also made of 5 mice each. Chromosome and micronuclei from bone marrow cells and comet slides from leukocytes were examined following standard protocols. The results demonstrated that MWCNTs exposure significantly increased (P < 0.05) the number of structural chromosomal aberrations, the frequency of micronucleated cells and the level of DNA damage, and decreased the mitotic index in treated groups compared to control groups. MWCNTs were shown to be toxic at sufficiently high concentrations, however purified functionalized MWCNTs had a higher clastogenic/genotoxic potential compared to nonfunctionalized form of MWCNT. The results of our study suggest that exposure to MWCNT has the potential to cause genetic damage. Hence, careful monitoring should be done with respect to designing/synthesizing biocompatible carbon nanomaterials. Further characterization of their systemic toxicity, genotoxicity and carcinogenicity is also essential. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2010.     

The in vivo genotoxic effects of carvacrol and thymol in rat bone marrow cells

The aim of this study was to investigate the in vivo genotoxic effects of carvacrol and thymol in bone marrow cells of rats. In the present study, both carvacrol (10, 30, 50, and 70 mg/kg b.w.) and thymol (40, 60, 80, and 100 mg/kg b.w.) significantly induced the structural and total chromosome abnormalities (CA) for all treatment periods (6, 12, and 24 h) when compared with control in bone marrow cells of rats intraperitonally administered. Both carvacrol and thymol showed similar effects with the positive control urethane on induction of the percentage of structural and total CA at the highest concentrations except the effects of carvacrol for 6 h treatment (70 mg/kg b.w. and 100 mg/kg b.w., respectively). In addition, carvacrol induced the numerical CA at all concentrations when compared to control and at two highest concentrations (50 and 70 mg/kg b.w.) when compared to solvent control. Thymol also induced the numerical CA especially at the highest concentration (100 mg/kg b.w.) for all treatment periods. It was shown that there was a dose-dependent effect on induction of structural, numerical and total CA for both carvacrol and thymol. Carvacrol and thymol decreased the mitotic index (MI) in all the concentrations and treatment times when compared with control. Carvacrol showed the similar effects with EC on decreasing the MI at 70 mg/kg b.w. for 6 h, at 30 and 50 mg/kg b.w. for 12 h and at all concentrations for 24 h treatment periods. Thymol also showed a similar effect with urethane (ethyl carbamate, EC) on decreasing the MI at 60, 80, and 100 mg/kg b.w. for 6 h and at all concentrations for 24 h treatment periods. Test substances decreased the MI in a dose-dependent manner.     

Nandrolone androgenic hormone presents genotoxic effects in different cells of mice

Nandrolone is an androgenic–anabolic steroid (AAS) with diverse medical applications but taken indiscriminately by some to rapidly increase muscle mass. The aim of this study was to evaluate the genotoxic and clastogenic potential of nandrolone (deca‐durabolin®) in vivo in different cells of mice, using the comet assay and micronucleus test, respectively. The animals received subcutaneous injection of the three doses of the steroid (1.0, 2.5 and 5.0 mg kg^?1 body weight). Cytotoxicity was assessed by scoring 200 consecutive total polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE–NCE ratio). The results showed a significant dose‐related increase in the frequency of DNA damage in leukocytes, liver, bone marrow, brain and testicle cells at the three tested doses and a significant increase of the micronucleated polychromatic erythrocytes at all tested doses. Under our experimental conditions, the nandrolone steroid hormone showed genotoxic and clastogenic effects when administered subcutaneously to mice. Copyright © 2011 John Wiley & Sons, Ltd.     

Chemoprotective effects of hesperidin against genotoxicity induced by cyclophosphamide in mice bone marrow cells

The preventive effect of hesperidin as a flavonoid was investigated in mouse bone marrow cells against genotoxicty induced by cyclophosphamide. Mice were orally (gavages) pretreated with solutions of hesperidin at four different doses (50, 100, 200, and 400 mg/kg b.w.) for five consecutive days. Mice were injected intraperitoneally on the fifth day with cyclophosphamide (50 mg/kg b.w.) and killed after 24 h for the evaluation of micronucleated polychromatic erythrocytes (MnPCEs) and the ratio of PCE/(PCE+NCE) (polychromatic erythrocyte/ polychromatic erythrocyte + normochromatic erythrocyte). Three last doses of hesperidin significantly reduced frequency of MnPCEs induced by cyclophosphamide (p<0.0001). Hesperdin at dose 200 mg/kg b.w. reduced MnPCEs 2.37 time and also completely normalized PCE/ (PCE+NCE) ratio. Histological examination of bone marrow showed that hesperidin affected on proliferation and hyper cellularity of immature myeloid elements in bone marrow that reduced by cyclophsopahmide. It is obvious that hesperidin, may with antioxidative activity, reduced the oxidative stress and genotoxicity induced by cyclophosphamide in mouse bone marrow cells.     

Cytogenetic evaluation of functionalized single‐walled carbon nanotube in mice bone marrow cells

With their unique structure and physicochemical properties, single\‐walled carbon nanotubes (SWCNTs) have many potential new applications in medicine and industry. However, there is lack of detailed information concerning their impact on human health and the environment. The aim of this study was to assess the effects, after intraperitoneal injection of functionalized SWCNTs (f‐SWCNT) on the induction of reactive oxygen species (ROS), frequency of structural chromosomal aberrations (SCA), frequency of micronuclei induction, mitotic index, and DNA damage in Swiss–Webster mice. Three doses of f‐SWCNTs (0.25, 0.5, and 0.75 mg/kg) and two controls (negative and positive) were administered to mice, once a day for 5 days. Bone marrow and peripheral blood samples were collected 24 h after the last treatment following standard protocols. F ‐ SWCNT exposure significantly enhanced ROS, increased (p < 0.05) the number of SCA and the frequency of micronucleated cells, increased DNA damage, and decreased the mitotic index in exposed groups compared to negative control. The scientific findings reported here suggest that purified f‐SWCNT have the potential to induce oxidative stress mediated genotoxicity in Swiss–Webster mice at higher level of exposure. Further characterization of their systemic toxicity, genotoxicity, and carcinogenicity is also essential. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1091–1102, 2016.     

Naloxone blocks anxiolytic-like effects of benzodiazepines in Swiss but not in Balb/c mice

 The ability of naloxone to block the effects of the benzodiazepines chlordiazepoxide and diazepam was evaluated in Swiss and Balb/c mice subjected to the light/dark choice test of anxiety or to a choice paradigm for measuring spontaneous exploratory behaviour. In Swiss mice, naloxone (5 or 10 mg/kg) completely or partially suppressed the anxiolytic-like effects of chlordiazepoxide (5 mg/kg) and diazepam (1 mg/kg) in the light/dark test. Naloxone alone was ineffective. None of these compounds affected locomotion in the free exploratory test. In Balb/c mice, naloxone did not reduce the anxiolytic-like action of benzodiazepines in the light/dark test. Moreover, naloxone did not antagonize the decrease in neophobia observed after anxiolytic treatment in Balb/c mice in the free exploratory paradigm. In this strain, benzodiazepines produced an increase of locomotor activity, whereas naloxone decreased it. The stimulant effects of benzodiazepines on locomotor activity were abolished by naloxone. As naloxone (2 mg/kg) reversed the morphine-induced hyperthermia both in Swiss and in Balb/c mice, differences in possible pharmacokinetic factors between the two strains can be ruled out as an explanation for the failure of naloxone to antagonize anxiolytic-like effects in Balb/c mice. Therefore, the ability of naloxone to reverse anxiolytic effects does not hold for all strains of mice. Received: 19 April 1996 / Final version: 22 November 1996     

Cytogenetic effects of commercial formulations of deltamethrin and/or thiacloprid on wistar rat bone marrow cells

Deltamethrin (DEL) and thiacloprid (THIA) are two insecticides that are widely used in agriculture either separately or in combination. Studies on genotoxicity and cytotoxicity of TIA and the mixture of DEL and THIA insecticides have not been reported so far. Therefore, we investigated the cytotoxic and genotoxic effects of commercial formulations DEL and/or THIA in rat bone marrow cells, using mitotic index (MI), micronucleus (MN) and chromosome aberrations (CA) assay. In vivo cytokinesis‐block micronucleus ( CBMN) assay using cytochalasin‐B in bone marrow cells was performed for the first time in this study. Rats were orally gavaged with a single dose of DEL (15 mg/kg), THIA (112.5 mg/kg) or DEL + THIA (15 + 112.5 mg/kg) for 24 h (acute treatments), or DEL (3 mg/kg/day), THIA (22.5 mg/kg/day) or DEL + THIA (3 + 22.5 mg/kg/day) for 30 days (subacute treatments). A corn oil vehicle control group and cyclophosphamide (50 mg/kg) positive control group were also included. All DEL and/or THIA treatments significantly decreased MI and binucleated (BN) cell numbers, and significantly increased CA, as compared to the vehicle control group. The results of CBMN assay indicated that the combination of DEL and THIA for both treatment times and the 30‐day treatment with THIA alone caused a significant increase in micronucleus formation in BN cells. The present findings indicated the combined exposure of DEL and THIA showed genotoxic and cytotoxic effects more than those of individual exposure of DEL or THIA in rat bone marrow cells. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 524–531, 2013.     

Lack of genotoxic effect of food dyes amaranth,sunset yellow and tartrazine and their metabolites in the gut micronucleus assay in mice

The food dyes amaranth, sunset yellow and tartrazine were administered twice, at 24 h intervals, by oral gavage to mice and assessed in the in vivo gut micronucleus test for genotoxic effects (frequency of micronucleated cells) and toxicity (apoptotic and mitotic cells). The concentrations of each compound and their main metabolites (sulfanilic acid and naphthionic acid) were measured in faeces during a 24-h period after single oral administrations of the food dyes to mice. Parent dye compounds and their main aromatic amine metabolites were detected in significant amounts in the environment of colonic cells. Acute oral exposure to food dye additives amaranth, sunset yellow and tartrazine did not induce genotoxic effect in the micronucleus gut assay in mice at doses up to 2000 mg/kg b.w. Food dyes administration increased the mitotic cells at all dose levels when compared to controls. These results suggest that the transient DNA damages previously observed in the colon of mice treated by amaranth and tartrazine by the in vivo comet assay [Sasaki, Y.F., Kawaguchi, S., Kamaya, A., Ohshita, M., Kabasawa, K., Iwama, K., Taniguchi, K., Tsuda, S., 2002. The comet assay with 8 mouse organs: results with 39 currently used food additives. Mutat. Res. 519, 103–119] are unable to be fixed in stable genotoxic lesions and might be partly explained by local cytotoxicity of the dyes.     

Synthesis,characterization, and determination of genotoxic effect of a novel dimeric 8-hydroxyquinoline Cd(II) SCN complex

In this study, a Cd(II) complex was synthesized using 8-hydroxyquinoline and thiocyanate as the ligands and structurally characterized with the combination of FTIR, ¹H-NMR, ¹³C-NMR, UV–vis, and MS spectral data. Then, genotoxic effects of the prepared complex were investigated. Genotoxic properties of the dimeric 8-hydroxyquinolinthiocyanatoCd(II) [Cd₂(8Q)₂(SCN)₂] complex synthesized as drug raw material were analyzed in human peripheral blood lymphocytes. Concentrations of 1, 2, 4, 6, and 8?μg/mL [Cd₂(8Q)₂(SCN)₂] were used for 24 and 48 h durations. [Cd₂(8Q)₂(SCN)₂] significantly increased chromosomal aberrations (CAs) at 4, 6, and 8?μg/mL concentrations after a 24-?h period and 2 and 4?μg/mL after a 48-h period. [Cd₂(8Q)₂(SCN)₂] significantly decreased the mitotic index (MI) at all concentrations, both at 24 and 48?h. Micronuclei frequency (MN) was not affected by [Cd₂(8Q)₂(SCN)₂] treatment compared with the control. After application for a 48?h period, 6 and 8?μg/mL concentrations showed toxic effects both in chromosomal abnormality and in micronucleus tests. It also decreased the cytokinesis-block proliferation index (CBPI), but this result was statistically significant only at 6 and 8?μg/mL concentrations. In the comet assay (single-cell gel electrophoresis (SCGE)), significant increases in comet tail length, tail moment, and tail intensity were observed at all concentrations. [Cd₂(8Q)₂(SCN)₂] displays clastogenic effect in the concentrations used in human peripheral lymphocytes at chromosomal abnormality, micronucleus tests, and cytokinesis-block proliferation index parameters. Further studies should be conducted in other test systems to evaluate the complete genotoxic potential of [Cd₂(8Q)₂(SCN)₂].     

Assessment of cytotoxic and clastogenic effects of nimesulide: an NSAID drug in somatic cells of BALB/c mice in vivo

The in vivo genotoxicity of nimesulide, a sulfononilide nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic effects, was evaluated by employing a mouse in vivo chromosomal aberration test in bone marrow cells. Oral treatment of animals for 5 consecutive days with 1, 2.5, 5, and 7.5?mg/kg body weight of the drug resulted in a statistically nonsignificant reduction in mitotic index and increase in CAs/cell and percent abnormal metaphase. The results indicated that nimesulide does not induce cytotoxicity and is a weak clastogen in the bone marrow cells of the mouse in vivo. Thus, the drug presents a very weak genotoxic risk.     

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.     

Reproductive toxicity evaluation of vanadium in male mice

The reproductive toxicity of vanadium was studied in mice. Male Swiss mice were exposed to sodium metavanadate at doses of 0, 20, 40, 60, and 80 mg/kg per day given in the drinking water for 64 days. To evaluate the fertility of the vanadium-treated animals, males were mated with untreated females for 4 days. A significant decrease in the pregnancy rate was observed at 60 and 80 mg/kg per day of sodium metavanadate. However, metavanadate did not reduce fertility in male mt 20 and 40 mg/kg per day. Reproductive toxicity was measured by sperm count, sperm motility, organ weights, and histologic evaluation of the testes. Decreased body and epididymis weight was only observed in the 80 mg/kg per day group, while testicular weights were not altered by the treatment with all doses used. Sperm coung was significantly decreased at 40, 60, and 80 mg/kg per day, but the sperm motility was unaffected. Histopathological examination revealed that the testes were normal and that the epididymis of treated male mice contained normal appearing sperm. The no observed adverse effect level (NOAEL) was 40 mg/kg per day. Consequently, vanadium would not cause any adverse effect on fertility or testicular function in male mice at the concentrations usually ingested by humansthrough the diet and drinking water.