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Micronuclei

Distribution by Scientific Domains

Life Sciences	60%
Medical Sciences	22%
Earth and Environmental Science	11%

Selected Abstracts

Genotoxicity testing of the herbicide trifluralin and its commercial formulation Treflan using the piscine micronucleus test

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 6 2008
Serpil Könen
Abstract In this study, the genotoxic effects of a widely used herbicide, trifluralin, and its commercial formulation, Treflan, were evaluated using the micronucleus test in a commercially important fish species, Oreochromis niloticus (Nile Tilapia). Fish were exposed to 1, 5, and 10 ,g/L doses of trifluralin and Treflan for 3, 6, and 9 days under laboratory conditions. Ethylmethanesulfonate, at a single dose of 10 mg/L, was used as positive control. Micronuclei were evaluated on the peripheral erythrocytes. Both Treflan and trifluralin treatments significantly increased the micronucleus frequencies in peripheral erythrocytes of O. niloticus. Furthermore, the genotoxicity of the active ingredient, trifluralin, was observed to be higher than that of the commercial formulation Treflan. Our results indicate that herbicide trifluralin has genotoxic potential in fish. Environ. Mol. Mutagen., 2008. © 2008 Wiley-Liss, Inc. [source]

Micronuclei and chromatid buds are the result of related genotoxic events

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2001
Luis Serrano-García
Abstract Chromatin buds (CHB), broken eggs, or budding cell nuclei are structures similar to micronuclei (MN) in shape, structure, and size, which are linked to the main nuclei of cells by a thread or stalks of chromatin. They have been observed in numerous cell types and there are reports of their existence relating them with MN or with genotoxic events. However, there is no systematic study reporting their frequency and no experiment has been done to ascertain whether they are really induced by genotoxins. Furthermore, they have been discarded as genotoxic events with the argument that they are not formed in dividing cells. Studies are presented here that indicate that CHB can be considered as genotoxic events and that their origin is comparable to that of MN. Bromodeoxyuridine (BrdU) was used to label proliferating lymphocytes, which were later identified by means of an immunohistochemical method, using the H2O2,DAB stain. The results show that CHB are consistently formed where MN are seen. CHB were induced by the clastogen mitomycin C (MMC) as well as by the aneuploidogen colcemid, with frequencies similar to MN in both cases, and to multinucleated cells in the case of colcemid. CHB occur in lymphocytes of smokers with frequencies similar to those of MN, and we found that the infection with Taenia solium metacestodes induced a comparable increase of both MN and CHB frequency in lymphocytes from pigs. Environ. Mol. Mutagen. 38:38,45, 2001 © 2001 Wiley-Liss, Inc. [source]

Analysis of micronuclei in blue mussels and fish from the Baltic and North Seas

ENVIRONMENTAL TOXICOLOGY, Issue 4 2004
Janina Bar
Abstract Micronuclei (MN) were analyzed in erythrocytes of flounder (Platichthys flesus) and wrasse (Symphodus melops) and in gill cells of blue mussels (Mytilus edulis). The organisms were collected from three study stations in the Baltic Sea and from seven stations in the North Sea (Karmsund area, Norway) 4 times. The statistically significant differences obtained were related to the season, sex of the fish, and sampling locality. Higher MN frequencies were found in fish and mussels collected from the most polluted study stations in the North Sea. The same tendency could be described in the Baltic Sea; however, it was masked by the recent oil spill from the Butinge oil terminal. Our results showing higher MN frequencies in presumably what were the most polluted study locations suggest that MN tests in fish and mussels may be used for the detection of genotoxic effects in a marine environment. The endpoint is well characterized and can be easily recognized, and the technique is convenient to use in field samplings following standard procedures and protocols. © 2004 Wiley Periodicals, Inc. Environ Toxicol 19: 365,371, 2004. [source]

Cytogenetic status in newborns and their parents in Madrid: The BioMadrid study

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2010
Virginia Lope
Abstract Monitoring cytogenetic damage is frequently used to assess population exposure to environmental mutagens. The cytokinesis-block micronucleus assay is one of the most widely used methods employed in these studies. In the present study we used this assay to assess the baseline frequency of micronuclei in a healthy population of father-pregnant woman-newborn trios drawn from two Madrid areas. We also investigated the association between micronucleus frequency and specific socioeconomic, environmental, and demographic factors collected by questionnaire. Mercury, arsenic, lead, and cadmium blood levels were measured by atomic absorption spectrometry. The association between micronucleated cell frequency and the variables collected by questionnaire, as well as, the risk associated with the presence of elevated levels of metals in blood, was estimated using Poisson models, taking the number of micronucleated cells in 1,000 binucleated cells (MNBCs) as the dependent variable. Separate analyses were conducted for the 110 newborns, 136 pregnant women, and 134 fathers in whom micronuclei could be assessed. The mean number of micronucleated cells per 1,000 binucleated cells was 3.9, 6.5, and 6.1 respectively. Our results show a statistically significant correlation in MNBC frequency between fathers and mothers, and between parents and newborns. Elevated blood mercury levels in fathers were associated with significantly higher MNBC frequency, compared with fathers who had normal mercury levels (RR:1.21; 95%CI:1.02,1.43). This last result suggests the need to implement greater control over populations which, by reason of their occupation or life style, are among those most exposed to this metal. Environ. Mol. Mutagen., 2010. © 2009 Wiley-Liss, Inc. [source]

Radioprotective effects of Daflon against genotoxicity induced by gamma irradiation in human cultured lymphocytes

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 9 2009
Seyed Jalal Hosseinimehr
Abstract The ability of Daflon to protect against genotoxicity induced by gamma irradiation has been investigated in vivo and in vitro in cultured lymphocytes from healthy human volunteers. Peripheral human blood samples were collected predose (10 min before) and 1, 2, and 3 hr after a single oral ingestion of 1000 mg of Daflon. At each time point, whole blood was exposed in vitro to 150 cGy of cobalt-60 gamma rays, and then the lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis-blocked binucleated cells. For each volunteer, the results showed a significant increase in the incidence of micronuclei after exposure to gamma irradiation as compared to control unexposed samples. As early as 1 hr after Daflon administration, a significant decrease in the incidence of micronuclei was observed in comparison with similarly irradiated lymphocytes collected before administration. The maximum protection was reached 1 hr after administration of Daflon with a significant decrease in the frequency of micronuclei of 40%. These findings suggest the possible application of Daflon for the protection of human lymphocytes from the genetic damage and side effects induced by gamma irradiation. Environ. Mol. Mutagen. 2009. © 2009 Wiley-Liss, Inc. [source]

Arsenate and dimethylarsinic acid in drinking water did not affect DNA damage repair in urinary bladder transitional cells or micronuclei in bone marrow,

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 9 2009
Amy Wang
Abstract Arsenic is a human skin, lung, and urinary bladder carcinogen, and may act as a cocarcinogen in the skin and urinary bladder. Possible modes of action of arsenic carcinogenesis/cocarcinogenesis include oxidative stress induction and inhibition of DNA damage repair. We investigated the effects of arsenic in drinking water on DNA damage repair in urinary bladder transitional cells and on micronucleus formation in bone marrow. F344 rats were given 100 ppm arsenate [As(V)] or dimethylarsinic acid [DMA(V)] in drinking water for 1 week. The in vivo repair of cyclophosphamide (CP)-induced DNA damage resulting from a single oral gavage of CP, and the in vitro repair of hydrogen peroxide (H2O2)- or formaldehyde-induced DNA damage, resulting from adding H2O2 or formaldehyde into cell medium, were measured by the Comet assay. DMA(V) effects were not observed on either CP-induced DNA damage induction or on DNA repair. Neither DMA(V) nor As(V) increased the H2O2 - or formaldehyde-induced DNA damage, and neither inhibited the repair of H2O2 -induced DNA damage. Neither DMA(V) nor As(V) increased the micronucleus frequency, nor did they elevate micronucleus frequency resulting from CP treatment above the level observed by the treatment with CP alone. These results suggest that arsenic carcinogenesis/cocarcinogenesis in the urinary bladder may not be via DNA damage repair inhibition. To our knowledge this is the first report of arsenic effects on DNA damage repair in the urinary bladder. Environ. Mol. Mutagen. 2009. Published 2009 by Wiley-Liss, Inc. [source]

Centrosome amplification induced by the antiretroviral nucleoside reverse transcriptase inhibitors lamivudine, stavudine, and didanosine

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 8 2009
Mia Yu
Abstract In cultured cells, exposure to the nucleoside reverse transcriptase inhibitor (NRTI) zidovudine (AZT) induces genomic instability, cell cycle arrest, micronuclei, sister chromatid exchanges, and shortened telomeres. In previous studies, we demonstrated AZT-induced centrosome amplification (>2 centrosomes/cell). Here, we investigate centrosome amplification in cells exposed to other commonly used NRTIs. Experiments were performed using Chinese Hamster ovary (CHO) cells, and two normal human mammary epithelial cell (NHMEC) strains: M99005 and M98040, which are high and low incorporators of AZT into DNA, respectively. Cells were exposed for 24 hr to lamivudine (3TC), stavudine (d4T), didanosine (ddI), and thymidine, and stained with anti-pericentrin antibody. Dose response curves were performed to determine cytotoxicity and a lower concentration at near plasma levels and a 10 fold higher concentration were chosen for the experiments. In CHO cells, there was a concentration-dependent, significant (P < 0.05) increase in centrosome amplification for each of the NRTIs. In NHMEC strain M99005, an NRTI-induced increase (P < 0.05) in centrosome amplification was observed for the high concentrations of each NRTI and the low doses of 3TC and ddI. In NHMEC strain M98040, the high doses of ddI and d4T showed significant increases in centrosome amplification. Functional viability of amplified centrosomes was assessed by arresting microtubule nucleation with nocodazole. In cells with more than two centrosomes, the ability to recover microtubule nucleation was similar to that of unexposed cells. We conclude that centrosome amplification is a consequence of exposure to NRTIs and that cells with centrosome amplification are able to accomplish cell division. Environ. Mol. Mutagen., 2009. © 2009 Wiley-Liss, Inc. [source]

Protective effect of the cruciferous vegetable mustard leaf (Brassica campestris) against in vivo chromosomal damage and oxidative stress induced by ,-radiation and genotoxic chemicals

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 5 2008
Ashu B. Tiku
Abstract We evaluated the possible protective effect of the popular Indian cruciferous vegetable mustard leaf (Brassica campestris) against chromosomal damage and oxidative stress induced by ,-radiation, cyclophosphamide (CPH) and urethane (URE), in mice. In vivo bone marrow micronucleus test was performed to assess chromosomal damage, and oxidative stress was monitored by estimating the changes in lipid peroxidation and the status of glutathione (GSH) as well as redox cycle antioxidants. Pretreatment with 50,250 mg/kg body wt of mustard leaf extract (MLE) for seven days significantly reduced the frequencies of micronuclei induced by ,-radiation, CPH and URE. The protective effect against chromosomal damage was associated with modulation of lipid peroxidation as well as an increase in GSH and the GSH-dependent enzyme glutathione S -transferase (GST). Mass spectral analysis showed the presence of glucosinolates in MLE used for the pretreatment of mice. These findings indicate that intake of the green leafy cruciferous vegetable mustard leaf can lead to protection against in vivo genotoxicity and oxidative stress. Environ. Mol. Mutagen., 2008. © 2008 Wiley-Liss, Inc. [source]

Evaluation of river water genotoxicity using the piscine micronucleus test

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 6 2007
Serap Ergene
Abstract The Berdan River, which empties into the Mediterranean Sea on the east coast of Turkey, receives discharges of industrial and municipal waste. In the present study, the in vivo piscine micronucleus (MN) test was used to evaluate the genotoxicity of water samples collected from different locations along the Berdan River. Nile tilapia (Oreochromis niloticus) were exposed in the laboratory for 2, 4, and 6 days, and micronuclei were evaluated in peripheral blood erythrocytes, gill cells, and caudal fin epithelial cells. A single dose of 5 mg/L cyclophosphamide was used as a positive control. In addition to micronuclei, nuclear abnormalities (NAs), such as binucleated cells and blebbed, notched, and lobed nuclei, were assessed in the erythrocytes, and chemical analyses were carried out to determine the amount of heavy metals in the water samples. MN and NA frequencies were significantly elevated (up to 2- to 3-fold) in fish exposed to river water samples taken downstream of potential discharges, and the elevated responses in gill and fin cells were related to the concentration of heavy metals in the water. MN frequencies (expressed as micronucleated cells/1,000 cells), in both treated and untreated fish, were greatest in gill cells (range: 0.80,3.70), and generally lower in erythrocytes (range: 0.50,2.80), and fin cells (range: 0.45,1.70). The results of this study indicate that the Berdan River is contaminated with genotoxic pollutants and that the genotoxicity is related to the discharge of wastes into the river water. Environ. Mol. Mutagen., 2007. © 2007 Wiley-Liss, Inc. [source]

Feasibility of conducting the micronucleus test in circulating erythrocytes from different mammalian species: An anatomical perspective

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 9 2006
Ion Udroiu
Abstract The in vivo mammalian micronucleus test can be conducted easily on peripheral blood samples since the maturation of erythrocytes involves the loss of the major nucleus. In addition, mature erythrocytes are relatively long-lived, so that the test potentially can detect genotoxic damage caused by chronic exposures. However, some species have spleens that remove micronuclei from the peripheral circulation, making such measurements problematical. This report summarises haematological and mutagenesis studies dealing with this subject and provides an anatomical interpretation of the phenomenon. Anatomical features can be used to identify those species in which micronuclei are removed by the spleen. Environ. Mol. Mutagen., 2006. © 2006 Wiley-Liss, Inc. [source]

Detection of clastogenic and aneugenic damage in newborn rats

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 5 2006
Ion Udroiu
Abstract The last 25 years have seen an ever-growing use of the erythrocyte micronucleus test for measuring damage to mammalian chromosomes in vivo. In addition, staining micronuclei with antikinetochore antibodies from CREST serum discriminates aneugenic from clastogenic damage. The use of the micronucleus test in rats, however, has been problematic because the spleen of adult rats efficiently removes micronucleated erythrocytes from the blood. In the present study, we have treated 5-day-old rats with either X-rays (a clastogen) or vinblastine (an aneugen) and measured micronuclei in erythrocytes from the blood and liver. Each treatment increased the frequency of micronuclei in both tissues, with the percentages of CREST-staining micronuclei reflecting the mechanism of micronucleus induction by the two agents. The results indicate that performing the micronucleus assay in the liver and peripheral blood of 5-day-old rats may be a useful approach for detecting the in vivo genotoxicity of chemical and physical agents. Environ. Mol. Mutagen., 2006. © 2006 Wiley-Liss, Inc. [source]

Effect of mangiferin on radiation-induced micronucleus formation in cultured human peripheral blood lymphocytes

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2005
Ganesh Chandra Jagetia
Abstract Irradiation causes a variety of lesions in important biomolecules of the cell through generation of free radicals leading to genomic instability. DNA strand breaks, acentric fragments, or defective kinetochores are manifested as micronuclei after the first cell division. Chemicals that can trap free radicals may reduce the deleterious effects of ionizing radiation. Mangiferin (MGN), a glucosylxanthone derived from Mangifera indica (mango), was investigated for its ability to reduce the frequency of radiation-induced micronucleated binucleate cells (MNBNCs) in cultured human peripheral blood lymphocytes (HPBLs). HPBL cultures were pretreated with 0, 5, 10, 20, 50, and 100 ,g/ml of MGN for 30 min before exposure to 3 Gy of 60Co ,-radiation. The maximum decline in radiation-induced micronuclei was observed at a concentration of 50 ,g/ml MGN; thereafter, a nonsignificant elevation in MNBNC frequency was observed at 100 ,g/ml MGN. Since the lowest MNBNC frequency was observed for 50 ,g/ml MGN, dose-response studies were undertaken using this concentration. Irradiation of HPBLs with 0, 1, 2, 3, or 4 Gy of ,-radiation caused a dose-dependent elevation in the MNBNC frequency, while treatment of HPBLs with 50 ,g/ml MGN 30 min before radiation resulted in significant declines in these frequencies. MGN alone did not alter the proliferation index. Irradiation caused a dose-dependent decline in the proliferation index, while treatment of HPBLs with 50 ,/ml MGN significantly elevated the proliferation index in irradiated cells. MGN treatment reduced hydrogen peroxide-induced lipid peroxidation in HPBLs in a concentration-dependent fashion. In cell-free studies, MGN inhibited the induction of ·OH (hydroxyl), O2·, (superoxide), DPPH (1,1-diphenyl-2-picrylhydrazyl), and ABTS·+ (2,2-azino-bis-3-ethyl benzothiazoline-6-sulphonic acid) radicals in a dose-dependent manner. The results of this study indicate that MGN possesses radioprotective properties by suppressing the effects of free radicals. Environ. Mol. Mutagen. 45:000,000, 2005. © 2005 Wiley-Liss, Inc. [source]

Genotoxicity of inorganic lead salts and disturbance of microtubule function

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2005
Daniela Bonacker
Abstract Lead compounds are known genotoxicants, principally affecting the integrity of chromosomes. Lead chloride and lead acetate induced concentration-dependent increases in micronucleus frequency in V79 cells, starting at 1.1 ,M lead chloride and 0.05 ,M lead acetate. The difference between the lead salts, which was expected based on their relative abilities to form complex acetato-cations, was confirmed in an independent experiment. CREST analyses of the micronuclei verified that lead chloride and acetate were predominantly aneugenic (CREST-positive response), which was consistent with the morphology of the micronuclei (larger micronuclei, compared with micronuclei induced by a clastogenic mechanism). The effects of high concentrations of lead salts on the microtubule network of V79 cells were also examined using immunofluorescence staining. The dose effects of these responses were consistent with the cytotoxicity of lead(II), as visualized in the neutral-red uptake assay. In a cell-free system, 20,60 ,M lead salts inhibited tubulin assembly dose-dependently. The no-observed-effect concentration of lead(II) in this assay was 10 ,M. This inhibitory effect was interpreted as a shift of the assembly/disassembly steady-state toward disassembly, e.g., by reducing the concentration of assembly-competent tubulin dimers. The effects of lead salts on microtubule-associated motor-protein functions were studied using a kinesin-gliding assay that mimics intracellular transport processes in vitro by quantifying the movement of paclitaxel-stabilized microtubules across a kinesin-coated glass surface. There was a dose-dependent effect of lead nitrate on microtubule motility. Lead nitrate affected the gliding velocities of microtubules starting at concentrations above 10 ,M and reached half-maximal inhibition of motility at about 50 ,M. The processes reported here point to relevant interactions of lead with tubulin and kinesin at low dose levels. Environ. Mol. Mutagen., 2005. © 2005 Wiley-Liss, Inc. [source]

Cytogenetic damage in female Chilean agricultural workers exposed to mixtures of pesticides

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2005
Carolina Márquez
Abstract The VIII Region of Bío-Bío is a major fruit-growing area of Chile that makes intensive use of agricultural pesticides. The cytogenetic damage associated with exposure to mixtures of pesticides was evaluated by comparing peripheral blood lymphocyte micronucleus (MN) frequencies in a group of 64 female agricultural workers and 30 female controls. The exposed subjects worked during the spring and summer in thinning and pruning fruit trees and in harvesting and packing different fruits, such as raspberries, grapes, apples, and kiwis. They did not use any protective measures during their work activities. A significant increase in the frequency of binucleated cells with micronuclei (BNMN) was found in the exposed women as compared with the controls (36.94 ± 14.47 vs. 9.93 ± 6.17 BNMN/1000 BN cells; P < 0.001). The frequency of BNMN varied as a function of age in both the exposed and control groups, but no correlation was found between BNMN frequency and the duration of exposure. Also, smoking and other habits had no effect on MN frequency. Our study confirms that occupational exposure to pesticide mixtures results in cytogenetic damage. Environ. Mol. Mutagen., 2005. © 2004 Wiley-Liss, Inc. [source]

Genetic damage detected in CD-1 mouse pups exposed perinatally to 3,-azido-3,-deoxythymidine and dideoxyinosine via maternal dosing, nursing, and direct gavage

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2004
Jack B. Bishop
Abstract Human immunodeficiency virus (HIV)-infected pregnant women are administered nucleoside-analogue antiretrovirals to reduce maternal-infant viral transmission. The current protocol recommends treating newborns for 6 additional weeks postpartum. The treatment is effective, but the risk of drug-induced chromosomal damage in neonates remains undefined. We used a mouse model to investigate this concern. In a multigeneration reproductive toxicity study, female CD-1 mice received 3,-azido-3,-deoxythymidine (AZT) and dideoxyinosine (ddI) (50/250, 75/375, 150/750 mg/kg/day AZT/ddI) by gavage twice daily in equal fractions beginning prior to mating and continuing throughout gestation and lactation. Direct pup dosing (same regimen) began on postnatal day (PND) 4. Peripheral blood erythrocytes of male pups were screened for micronuclei, markers of chromosomal damage, on PNDs 1, 4, 8, and 21. Extraordinary increases in micronucleated cells were noted in pups for each treatment group at each sampling time; treated dams exhibited smaller yet significant increases in micronucleated erythrocytes. The frequencies of micronucleated cells in untreated pups were higher than in the untreated dams, and all pups had markedly elevated levels of circulating reticulocytes compared to dams. These observations suggest that fetal and neonatal mouse hematopoietic precursor cells have heightened sensitivity to genotoxic agents, perhaps due to rapid cell proliferation during the perinatal period of development. The amount of genetic damage observed in treated pups raises concern for the potential of similar damage in humans. Investigations of chromosomal integrity in exposed newborns and children are recommended. Environ. Mol. Mutagen. 43:3,9, 2004. © 2004 Wiley-Liss, Inc. [source]

Genetic toxicity of methamphetamine in vitro and in human abusers

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2003
Jih-Heng Li
Abstract Methamphetamine (METH) is a widely abused psychomotor stimulant. Although numerous studies have examined METH-induced neurotoxicity, its ability to produce genotoxic effects has not been evaluated. In this article, we report on the genotoxicity of METH in vitro and in human METH abusers. METH induced his+ revertants in Salmonella typhimurium strains TA98 and TA100, and increased the frequency of hprt mutants, micronuclei, and sister chromatid exchange (SCE) in cultured Chinese hamster ovary K1 (CHO-K1) cells. These METH-induced genotoxic effects were eliminated if METH exposure was conducted in the presence of rat liver S9, indicating that the genotoxicity was caused by METH, and not by metabolites of METH. In addition, reactive oxygen species (ROS) scavengers inhibited the METH-induced micronuclei in CHO-K1 cells. Further investigation with 76 human long-term METH abusers and 98 unexposed controls demonstrated that total METH exposure correlated with micronucleus and SCE frequencies in cultured lymphocytes. The results of this study indicate that METH is a genotoxic agent and that ROS may play a role in METH-induced genotoxicity. Environ. Mol. Mutagen. 42:233,242, 2003. © 2003 Wiley-Liss, Inc. [source]

Micronuclei and chromatid buds are the result of related genotoxic events

Evaluation of the rodent micronucleus assay by a 28-day treatment protocol: Summary of the 13th Collaborative Study by the Collaborative Study Group for the Micronucleus Test (CSGMT)/Environmental Mutagen Society of Japan (JEMS),Mammalian Mutagenicity Study Group (MMS)

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2001
Shuichi Hamada
Abstract To examine whether micronucleus tests can be incorporated into general toxicology assays, we performed micronucleus tests applying the treatment protocols typically used in such assays. In this 13th Collaborative Study of the CSGMT, both rats and mice were tested, although rats were used in the majority of the studies. Fifteen mutagens were tested in rats, mainly by oral (p.o.) administration. Micronucleus induction was evaluated 2, 3, and 4 days, and 1, 2, 3, and 28 days after the beginning of the treatment in the peripheral blood, and at 28 days in the bone marrow. Of the 15 chemicals that induced micronuclei in rats in short-term assays, two chemicals (1,2-dimethylhydrazine·2HCl and mitomycin C) were negative in all our experiments, possibly because of insufficient dose levels. The remaining 13 were positive within the estimated dose range of a general toxicology assay, suggesting the possibility of integrating the micronucleus assay into general toxicology assays. Three patterns were observed in micronucleus induction during the period of repeated treatment: (1) gradual increases in micronucleus frequency with sequential doses, (2) a peak at 3,5 days followed by gradual decreases in micronucleus frequency with sequential doses, and (3) a rapid increase in micronucleus frequency followed by a plateau. We evaluated factors that might have been involved in those patterns, such as the spleen function, target organ exposure, extramedullary hematopoiesis, hypothermia, and hypoxia. Another factor we considered was dosage. Because the dosages employed in a general toxicity assay are usually lower than those used in short-term micronucleus assays, this discrepancy was considered the greatest potential problem for integrating the micronucleus assay into general toxicology assays. Our results indicate that the integration of the micronucleus assay into a 28-day toxicological assay is feasible. To serve this purpose, blood samples collected 4 days after the beginning of treatment and blood and bone marrow samples collected at autopsy should be examined. Furthermore, although it is recognized that mice may be suitable for performing independent micronucleus assays, we propose that rats can provide biologically important and relevant information regarding potential chemical mutagens that can be evaluated under conditions used in the conduct of general toxicology studies. Environ. Mol. Mutagen. 37:93,110, 2001 © 2001 Wiley-Liss, Inc. [source]

Aluminum induces chromosome aberrations, micronuclei, and cell cycle dysfunction in root cells of Vicia faba

ENVIRONMENTAL TOXICOLOGY, Issue 2 2010
Min Yi
Abstract Aluminum (Al) exists naturally in air, water, and soil, and also in our diet. Al can be absorbed into the human body and accumulates in different tissues, which has been linked to the occurrence of Alzheimer's disease and various neurological disorders. By using Vicia cytogenetic tests, which are commonly used to monitor the genotoxicity of environmental pollutants, cytogenetic effects of aluminum (AlCl3) were investigated in this study. Present results showed that Al caused significant increases in the frequencies of micronuclei (MN) and anaphase chromosome aberrations in Vicia faba root tips exposed to Al over a concentration-tested range of 0.01,10 mM for 12 h. The frequency of micronucleated cells was higher in Al-treated groups at pH 4.5 than that at pH 5.8. Similarly, AlCl3 treatment caused a decrease in the number of mitotic cells in a dose- and pH-dependent manner. The number of cells in each mitotic phase changed in Al-treated samples. Mitotic indices (MI) decreased with the increases of pycnotic cells. Our results demonstrate that aluminum chloride is a clear clastogenic/genotoxic and cytotoxic agent in Vicia root cells. The V. faba cytogenetic test could be used for the genotoxicity monitoring of aluminum water contamination. © 2009 Wiley Periodicals, Inc. Environ Toxicol, 2010. [source]

Analysis of micronuclei in blue mussels and fish from the Baltic and North Seas

Frequencies of micronuclei in bank voles from zones of high radiation at Chornobyl, Ukraine

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2000
Brenda E. Rodgers
Abstract A population of Clethrionomys glareolus (bank vole) from a highly radioactive area within the Chornobyl, Ukraine exclusion zone was sampled in June 1997 and in June and October 1998. Internal radiation doses from radiocesium were estimated to be as high as 8 rads/d. Total dose, which takes into account the internal dose from radiostrontium and the surrounding environment, was estimated to be 15 to 20 rads/d. In contrast, individuals from a reference population lying outside of the exclusion zone registered negligible levels of contamination. We used the micronucleus test in a double-blind study to analyze blood samples from 58 individuals. We scored more than 600,000 polychromatic erythrocytes (PCEs) but could not reject the null hypothesis that the frequency of micronucleated PCEs in voles exposed to radiation was equal to the frequency in unexposed voles. Results of our study stand in sharp contrast to earlier reports of increased frequencies of micronuclei in rodents exposed to fallout of the Chornobyl accident, but with radiation doses that were orders of magnitude lower than those reported here. Radioresistance and experimental methods are possible explanations for these differences in the results. [source]

Anticlastogenic, antitoxic and sorption effects of humic substances on the mutagen maleic hydrazide tested in leguminous plants

EUROPEAN JOURNAL OF SOIL SCIENCE, Issue 3 2004
G. Ferrara
Summary The potential anticlastogenic and antitoxic effects of a soil humic acid (HA), a peat HA and a peat fulvic acid (FA) on the mutagen maleic hydrazide (MH) have been investigated in two legume species, Vicia faba and Pisum sativum. Both HAs and FA were tested at two different concentrations, 20 and 200 mg l,1, either alone or after 24-hour interaction with 10 mg l,1 of MH before addition to the legume seeds. Anticlastogenicity, i.e. an antimutagenic action defined as the capacity for minimizing chromosome breakages, was evaluated by counting both micronuclei (MN) and aberrant anatelophases (AAT) in root-tip cells. Length and dry weight of the seedling primary root were measured to test the antitoxic activity of HA and FA on MH. The possible occurrence and extent of adsorption or desorption of MH onto or from HA were also investigated. The two species responded differently to the anticlastogenic tests, with V. faba showing a greater number of MN and AAT anomalies than P. sativum. Peat HA and FA exhibited anticlastogenic and antitoxic activities of similar intensity and greater than those of soil HA. The adsorption capacity of both HAs for MH was small, thus suggesting that adsorption is not a major mechanism responsible for the reduction of clastogenicity and antitoxicity of MH by HA. [source]

Selective elimination of amplified CDK4 sequences correlates with spontaneous adipocytic differentiation in liposarcoma

GENES, CHROMOSOMES AND CANCER, Issue 11 2009
Zofia Hélias-Rodzewicz
Well-differentiated and undifferentiated liposarcomas are characterized by high-level amplifications of chromosome 12 regions including the CDK4 and MDM2 genes. These amplicons are either localized, in well-differentiated liposarcoma (WDLPS), on extrachromosomal structures (ring or rod chromosomes), or integrated into chromosome arms in undifferentiated tumors. Our results reveal that extrachromosomal amplicons are unstable, and frequently lost by micronucleation. This loss correlates with hypermethylation of eliminated sequences and changes of their replication time. Treatment of cells with demethylating agents during early S-phase significantly decreases the rate of micronuclei positive for CDK4. We also demonstrate that, in our model, micronuclei are generated during anaphase as a consequence of anaphase abnormalities (chromosome lagging and anaphase bridges). Finally, a dramatic increase of adipocytic differentiation was noted in cells that have eliminated copies of CDK4 gene in micronuclei. These findings provide evidence that, in WDLPS, adipocytic differentiation could be the consequence of CDK4 loss, an event occurring rarely in undifferentiated tumors in which the amplified sequences are integrated into chromosome arms. © 2009 Wiley-Liss, Inc. [source]

Nonselective DNA damage induced by a replication inhibitor results in the selective elimination of extrachromosomal double minutes from human cancer cells

GENES, CHROMOSOMES AND CANCER, Issue 10 2007
Noriaki Shimizu
Gene amplification plays a pivotal role in human malignancy. Highly amplified genes frequently localize to extrachromosomal double minutes (dmin), which usually segregate to daughter cells in association with mitotic chromosomes. We and others had shown that treatment with low-dose hydroxyurea (HU) results in the elimination of dmin and reversion of the cancer cell phenotype. HU treatment in early S-phase, when dmin are replicated, results in their detachment from chromosomes at the next M-phase, leading to the appearance of micronuclei enriched in dmin, followed by their elimination. In this article, we examined the effect of low-dose HU on the behavior of dmin in relation to DNA damage induction by simultaneously monitoring LacO-tagged dmin and phosphorylated histone H2AX (,H2AX). As expected, treatment with low-dose HU induced numerous ,H2AX foci throughout the nucleus in early S-phase, and these rarely coincided with dmin. Most chromosomal ,H2AX foci disappeared by metaphase, whereas, unexpectedly, those that persisted frequently associated with dmin. We found that these dmin aggregated, detached from anaphase chromosomes, and apparently formed micronuclei. Because ,H2AX foci likely represent DNA double strand breaks (DSBs), the response to DSBs sustained by extrachromosomal dmin appears to be different from that sustained by chromosomal loci, which may explain why DSB-inducing agents cause the selective elimination of dmin. © 2007 Wiley-Liss, Inc. [source]

Cytotoxicity and genotoxicity of sodium percarbonate: a comparison with bleaching agents commonly used in discoloured pulpless teeth

INTERNATIONAL ENDODONTIC JOURNAL, Issue 2 2010
M. R. Fernández
Fernández MR, Carvalho RV, Ogliari FA, Beira FA, Etges A, Bueno M. Cytotoxicity and genotoxicity of sodium percarbonate: a comparison with bleaching agents commonly used in discoloured pulpless teeth. International Endodontic Journal, 43, 102,108, 2010. Abstract Aim, To evaluate the cytotoxicity and genotoxicity of sodium percarbonate (SPC) in comparison with bleaching agents used on discoloured pulpless teeth. Methodology, The cytotoxicity and genotoxicity of bleaching agents were evaluated both in their pure form as well as at concentrations commonly used in clinical practice. Hydrogen peroxide (HP), carbamide peroxide (CP), sodium perborate (SP) and SPC were diluted in Dulbecco's modified Eagle's medium (DMEM) in series. To evaluate the cytotoxicity, the survival of 3T3/NIH mouse fibroblasts was measured photometrically using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after a 24 h-exposure period. Genotoxicity was indicated by micronuclei (MN) formation, and modification of the normal cell was analysed by light microscopy (400×). Statistical analysis was performed by one-way anova, followed by a multiple-comparison Tukey post hoc test (P < 0.05). Results, All groups exhibited a dose-dependent cytotoxicity. However, CP showed a similar cytotoxic effect when compared with DMEM-untreated control (UC) group. HP and SPC were significantly more cytotoxic than SP. The genotoxicity test showed that SPC and SP had an intermediate rate of MN frequency when compared with the UC group. The mean rate of MN frequency for HP was higher and statistically more significant than for the other groups tested. No difference was observed when CP and UC groups were compared. Conclusions, Sodium percarbonate showed cytotoxicity and genotoxicity similar to those of the other products tested. However, before SPC is used clinically, studies should be conducted to confirm its safety in vivo. [source]

Bystander signaling between glioma cells and fibroblasts targeted with counted particles

INTERNATIONAL JOURNAL OF CANCER, Issue 1 2005
Chunlin Shao
Abstract Radiation-induced bystander effects may play an important role in cancer risks associated with environmental, occupational and medical exposures and they may also present a therapeutic opportunity to modulate the efficacy of radiotherapy. However, the mechanisms underpinning these responses between tumor and normal cells are poorly understood. Using a microbeam, we investigated interactions between T98G malignant glioma cells and AG01522 normal fibroblasts by targeting cells through their nuclei in one population, then detecting cellular responses in the other co-cultured non-irradiated population. It was found that when a fraction of cells was individually irradiated with exactly 1 or 5 helium particles (3He2+), the yield of micronuclei (MN) in the non-irradiated population was significantly increased. This increase was not related to the fraction of cells targeted or the number of particles delivered to those cells. Even when one cell was targeted with a single 3He2+, the induction of MN in the bystander non-irradiated population could be increased by 79% for AG01522 and 28% for T98G. Furthermore, studies showed that nitric oxide (NO) and reactive oxygen species (ROS) were involved in these bystander responses. Following nuclear irradiation in only 1% of cells, the NO level in the T98G population was increased by 31% and the ROS level in the AG0 population was increased by 18%. Treatment of cultures with 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (c-PTIO), an NO scavenger, abolished the bystander MN induction in non-irradiated AG01522 cells but only partially in non-irradiated T98G cells, and this could be eliminated by treatment with either DMSO or antioxidants. Our findings indicate that differential mechanisms involving NO and ROS signaling factors play a role in bystander responses generated from targeted T98G glioma and AG0 fibroblasts, respectively. These bystander interactions suggest that a mechanistic control of the bystander effect could be of benefit to radiotherapy. © 2005 Wiley-Liss, Inc. [source]

Genotoxicity of pyrrolizidine alkaloids,,

JOURNAL OF APPLIED TOXICOLOGY, Issue 3 2010
Tao Chen
Abstract Pyrrolizidine alkaloids (PAs) are common constituents of many plant species around the world. PA-containing plants are probably the most common poisonous plants affecting livestock and wildlife. They can inflict harm to humans through contaminated food sources, herbal medicines and dietary supplements. Half of the identified PAs are genotoxic and many of them are tumorigenic. The mutagenicity of PAs has been extensively studied in different biological systems. Upon metabolic activation, PAs produce DNA adducts, DNA cross-linking, DNA breaks, sister chromatid exchange, micronuclei, chromosomal aberrations, gene mutations and chromosome mutations in vivo and in vitro. PAs induced mutations in the cII gene of rat liver and in the p53 and K- ras genes of mouse liver tumors. It has been suggested that all PAs produce a set of (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H -pyrrolizine-derived DNA adducts and similar types of gene mutations. The signature types of mutations are G,:,C , T,:,A transversion and tandem base substitutions. Overall, PAs are mutagenic in vivo and in vitro and their mutagenicity appears to be responsible for the carcinogenesis of PAs. Published in 2010 by John Wiley & Sons, Ltd. [source]

Naringin, a grapefruit flavanone, protects V79 cells against the bleomycin-induced genotoxicity and decline in survival

JOURNAL OF APPLIED TOXICOLOGY, Issue 2 2007
Abhinav Jagetia
Abstract The effect of naringin, a grapefruit flavonone was studied on bleomycin-induced genomic damage and alteration in the survival of cultured V79 cells. Exposure of V79 cells to bleomycin induced a concentration dependent elevation in the frequency of binucleate cells bearing micronuclei (MNBNC) and a maximum number of MNBNCs were observed in the cells treated with 50 ,g ml,1 bleomycin, the highest concentration evaluated. This genotoxic effect of bleomycin was reflected in the cell survival, where a concentration dependent decline was observed in the cells treated with different concentrations of bleomycin. Treatment of cells with 1 mm naringin before exposure to different concentrations of bleomycin arrested the bleomycin-induced decline in the cell survival accompanied by a significant reduction in the frequency of micronuclei when compared with bleomycin treatment alone. The cell survival and micronuclei induction were found to be inversely correlated. The repair kinetics of DNA damage induced by bleomycin was evaluated by exposing the cells to 10 ,g ml,1 bleomycin using single cell gel electrophoresis. Treatment of V79 cells with bleomycin resulted in a continuous increase in DNA damage up to 6 h post-bleomycin treatment as evident by migration of more DNA into the tails (% tail DNA) of the comets and a subsequent increase in olive tail moment (OTM), an index of DNA damage. Treatment of V79 cells with 1 mm naringin reduced bleomycin-induced DNA damage and accelerated DNA repair as indicated by a reduction in % tail DNA and OTM with increasing assessment time. A maximum reduction in the DNA damage was observed at 6 h post-bleomycin treatment, where it was 5 times lower than bleomycin alone. Our study, which was conducted on the basis of antioxidant, free radical scavenging and metal chelating properties of naringin demonstrates that naringin reduced the genotoxic effects of bleomycin and consequently increased the cell survival and therefore may act as a chemoprotective agent in clinical situations. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Genotoxicity study in lymphocytes of offset printing workers

JOURNAL OF APPLIED TOXICOLOGY, Issue 1 2006
Hüseyin Aksoy
Abstract The potential cytogenetic damage in offset printing workers was evaluated using sister chromatid exchanges (SCEs), chromosome aberrations (CAs) and micronuclei (MN) as biomarkers in peripheral lymphocytes of 26 volunteers (14 workers, 12 controls). The CA, SCE and MN frequency of offset printing workers was significantly higher than in their controls. The replication index (RI) was not affected while the mitotic index (MI) was affected most in the workers. It can be concluded from this study that chronic occupational exposure to printing dyes and thinner may lead to a slightly increased risk of genetic damage among offset printing workers. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Microsporogenesis and meiotic behavior in nine species of the genus Pinus

JOURNAL OF SYSTEMATICS EVOLUTION, Issue 4 2009
Hui-Sheng DENG
Abstract The meiotic behavior of 10 taxa (nine species and one variety) of the genus Pinus was investigated using pollen mother cells (PMCs) to reveal the differentiation among karyotypes. Chromosome spreads were prepared by conventional squashing. The meiotic index and the average configuration were higher, whereas the frequency of aberrance (chromosomal bridges, fragments, or micronuclei) was lower, in all 10 taxa compared with other gymnosperms. The meiotic index, average configuration, and frequency of irregularity were found to be uniform among the species. It was shown that the genomes of the Pinus species investigated were highly stable, confirming results of previous mitotic analyses in this genus. However, slight differentiation of homologous chromosomes among genomes was revealed by analysis of meiotic configurations in Pinus nigra var. poiretiana. Quadrivalents were observed in 9.31% of PMCs in this species. This is the first time that quadrivalents have been observed in gymnosperms. [source]