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1.
Ecotoxicol Environ Saf ; 203: 110989, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888600

RESUMO

AIM: The city of L'Aquila (central Italy) was hit by a strong earthquake in 2009 that caused the collapse of several buildings, deaths and injured people. In the following years, a great number of building sites were activated, building workers resulted intensely exposed and represent a relevant target for research on environmental mutagenesis and epidemiological surveillance. Cells of buccal mucosa are considered an appropriate site for early detecting of cytogenetic damage, since it represents the first barrier in inhalation or ingestion and can metabolize carcinogenic agents into reactive chemicals. Our study is aimed 1) at comparing the early genotoxic damage as measured by the buccal mucosa micronucleus test in two subgroups of workers defined by different occupational exposure and 2) at evaluating possible confounding variables such as lifestyle factors. METHODS AND RESULTS: A cross-sectional study was conducted in L'Aquila, on 24 outdoor workers (OWs) highly exposed on the construction sites and 26 indoor workers (IWs), all subjected to the compulsory occupational surveillance system, in the period 2017-2018. Buccal cells samples were collected and, based on the Micronucleus test, the exfoliated cells were classified in respect of nuclear changes observed. Moreover, a self-report questionnaire composed of 84 items, was administered to the workers. RESULTS: Significant differences were observed between Exp+ (OWs) and Exp- (IWs) in the number of the analyzed cells (expressed as mean value out of 1000 cells): respectively 954.46 vs 990.06 normal cells, (p < 0.001); 19.79 vs 4.95 micronucleated cells, as marker of chromosomal damage (p < 0.001); 13.93 vs 8.96 binucleated cells, as marker of failed cytokinesis (p < 0.001); 2.09 vs 1.18 karyolytic cells, as marker of cell death and damaged DNA (p < 0.05). According with a multivariate regression analysis, in addition to the job exposure (OW vs IW, beta = 12.221, p < 0.001), the only variable independently associated with an increase in Micronuclei (MNs) is the smoking habit (OWs vs IWs, beta = 6.683, p < 0.001) which, even if not associated with dust exposure, worsens cell integrity. Moreover, this worsening effect is weaker in workers not exposed to the site dust (moderation effect). Within social demographic factors, the high educational level only apparently seems to affect MNs number: even if unbalanced in favor of IWs vs OWs, this variable resulted a confounder, since its effect disappears when the interaction between these two factors is considered, because it is a covariate of smoking habit as well as of the job condition. CONCLUSION: Despite some limitation, our findings clearly confirm the role of occupational exposure as a marker of cytogenetic damage associated with MNs number in construction workers. Moreover, smoking status appears as the only other investigated factor independently associated to the outcome. The statistical model, in addition, highlights possible moderation and confounding effects, such as interaction between smoking and occupational exposure and the unbalanced school education level in workers. Micronucleus test in exfoliated buccal cells would be considered a suitable method for studying the early genotoxic damage in the construction occupational setting as well as in evaluating the efficacy of preventive practices.


Assuntos
Indústria da Construção , Dano ao DNA , Poeira , Mucosa Bucal/citologia , Exposição Ocupacional/efeitos adversos , Adulto , Estudos Transversais , Humanos , Itália , Masculino , Testes para Micronúcleos , Pessoa de Meia-Idade , Adulto Jovem
2.
Sci Total Environ ; 737: 140304, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32783869

RESUMO

Despite the damaging effects of pesticides glyphosate (Gly), atrazine (Atra) and fipronil (Fip) on different organisms, the mutagenic, genotoxic and morphotoxic potential of testudine erythrocytes in freshwater remains unknown. Thus, the aim of the present study is to assess the toxicological potential of these compounds in Podocnemis expansa (Amazonian turtles) neonates from eggs artificially incubated in substrate at different concentrations of herbicides Gly and Atra and insecticide Fip. Micronucleus test and other nuclear abnormalities, as well as comet assay and morphometric measurements taken of models' circulating erythrocytes were used as toxicity biomarkers. Pups exposed to Gly (groups Gly-65 ppb and Gly-6500 ppb) were the ones recording the largest amount of nuclear abnormalities; erythrocytes with multilobulated, notched and displaced nucleus were mostly frequent in groups Atra-2 ppb and Gly -65 ppb. All treatments (Gly-6500 ppb, Atra-2 ppb, Atra-200 ppb, Fip-4 ppb and Fip-400 ppb), except for group Gly-65 ppb, led to decreased erythrocyte area, increased "nuclear area: erythrocyte area" ratio, as well as to decreased erythrocyte and erythrocyte nuclei circularity, which highlights the clear effect on the size and shape of these cells. On the other hand, the comet assay did not evidence any genotoxic effect caused by the assessed pesticides. This is a pioneer study on the mutagenic and morphotoxic potential of pesticides in P. expansa eclodides exposed in ovo to Gly, Atra and Fip; therefore, it is an insight on how these compounds can affect the health of these animals.


Assuntos
Atrazina , Praguicidas , Animais , Dano ao DNA , Eritrócitos/efeitos dos fármacos , Humanos , Recém-Nascido , Testes para Micronúcleos , Mutagênicos
3.
Toxicol Lett ; 332: 202-212, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32659469

RESUMO

A variety of methods have been developed for accurate and systematic evaluation of chemical genotoxicity. Ceric ammonium nitrate (CAN) and 1,3-propane sultone (1,3-PS) have been extensively applied in industrial fields. Although 1,3-PS, but not CAN, has been reported as a potent carcinogen, systematic assessment of the genotoxic properties of these chemicals has not been conducted. The purpose of this study was to establish a decision tree for evaluating genotoxicity based on the good laboratory practices (GLP) system using 1,3-PS and CAN as test chemicals. In vitro studies were performed including the bacterial reverse mutation assay, chromosomal aberration assay, and micronucleus assay. We conducted in vivo studies using a combined micronucleus and alkaline comet (MN-CMT) assay and the Pig-a gene mutation assay, which is a promising method for detecting gene mutations in vivo. CAN showed negative responses in all in vitro genotoxicity assays and the in vivo combined MN-CMT assay. Meanwhile, 1,3-PS had positive results in all in vitro and in vivo genotoxicity assays. In this study, we confirmed the genotoxicity of 1,3-PS and CAN using both in vitro and in vivo assays. We propose a decision tree for evaluating chemical-induced genotoxicity.


Assuntos
Cério/toxicidade , Árvores de Decisões , Mutagênicos/toxicidade , Tiofenos/toxicidade , Animais , Bactérias/efeitos dos fármacos , Linhagem Celular/efeitos dos fármacos , Aberrações Cromossômicas/efeitos dos fármacos , Ensaio Cometa , Cricetinae , Cricetulus , Dano ao DNA , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Testes para Micronúcleos , Testes de Mutagenicidade , Ratos Sprague-Dawley
4.
Bull Environ Contam Toxicol ; 105(2): 224-229, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32710385

RESUMO

This study deals with bleak (Alburnus alburnus) sensitivity in detecting of the wastewater related pressure in large lowland rivers. The major objective was to investigate if the response measured in bleak should be linked to a certain stretch of the river and characterised as "stretch specific", or it should be linked to the sampling site and characterised as "site specific". The response was evaluated via condition index, metal pollution index, DNA damage and cell viability using integrated biomarker response approach. The study was conducted at 3 sub-sites characterized by different pollution levels in a relatively short stretch (2 km) of the Sava River (Serbia). Results indicated that the response of the biomarkers in bleak can be interpreted as "site specific". Among the studied biomarkers, DNA damage assessed by comet assay and micronucleus test has shown high sensitivity in differentiation of the sites.


Assuntos
Cyprinidae/crescimento & desenvolvimento , Dano ao DNA , Rios/química , Águas Residuárias/química , Poluentes Químicos da Água/análise , Animais , Ensaio Cometa , Cyprinidae/genética , Monitoramento Ambiental/métodos , Testes para Micronúcleos , Sérvia
6.
Mutat Res ; 854-855: 503197, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32660821

RESUMO

Telomeres, specialized structures at the ends of linear chromosomes, protect chromosome ends from degradation, recombination, and mis-repair. Critically short telomere length (TL) may result in chromosome instability (CIN), causing tumor promotion and, at higher levels, cell death and tumor suppression. Homocysteine (Hcy) is a sulfur-containing amino acid involved in one-carbon metabolism. Elevated plasma Hcy is a cancer risk factor. Human SH-SY5Y neuroblastoma cells were treated with pathophysiological concentrations of Hcy (15-120 µM) for 14 and 28 days. The cytokinesis-block micronucleus cytome assay was used to determine cytostasis (nuclear division index, NDI), cell death (apoptosis and necrosis), and CIN (micronuclei, nucleoplasmic bridges, and nuclear buds in binucleated cells). Quantitative PCR was used to measure TL and the expression of hTERT, the gene encoding the catalytic subunit of telomerase for TL elongation. The results showed that Hcy induced elongation of TL and fluctuating changes in expression of hTERT. TL elongation was associated with increased CIN. Hcy decreased the NDI and increased cell death. This study shows that there is cross-talk between Hcy and TL in tumor cells and supports the concept that high Hcy inhibits cell division and promotes the death of tumor cells by abnormal elongation of TL and elevation of CIN.


Assuntos
Instabilidade Cromossômica/genética , Homocisteína/genética , Neuroblastoma/genética , Telômero/genética , Apoptose/genética , Morte Celular/genética , Divisão Celular/genética , Linhagem Celular Tumoral , Citocinese/genética , Dano ao DNA/genética , Humanos , Micronúcleos com Defeito Cromossômico , Testes para Micronúcleos/métodos , Necrose/genética , Telomerase/genética
7.
Mutat Res ; 854-855: 503209, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32660823

RESUMO

We have measured the toxicity and genotoxicity of 2-methylfuran, which is formed in foods during thermal processing. The agent was administered by oral gavage to male Sprague-Dawley rats, daily for 28 days, before performing general toxicology analysis and the following genotoxicity tests: comet assay (peripheral blood, liver); Pig-a gene mutation assay (peripheral blood); micronucleus test (peripheral blood, bone marrow). Liver was the primary target organ; histological changes (oval cell hyperplasia) were observed but without significant changes in serum enzyme markers. For hepatotoxicity, the no-observed-adverse-effect level was 5 mg/kg bw/d. Histopathological changes were also seen in the bone marrow. Genotoxicity assays were uniformly negative.


Assuntos
Furanos/toxicidade , Animais , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Testes para Micronúcleos/métodos , Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Ratos , Ratos Sprague-Dawley
8.
Mutat Res ; 854-855: 503202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32660826

RESUMO

Cancer is a genomic disease associated with accumulation of genetic damage. Cancer-initiating events, such as chromosome breakage, loss and rearrangement, can be used as biomarkers to evaluate individual cancer risk. Cytokinesis-block micronucleus cytome (CBMN - Cyt) assay parameters in peripheral blood lymphocytes (PBL) of thirty four patients diagnosed with high-grade squamous intraepithelial lesions (HSIL) and fifteen healthy women were measured. The genomic instability of patients diagnosed with HSIL were investigated in order to compare differences between the two subgroups of HSIL (CIN 2 and CIN 3). The micronucleus (MN) frequencies in PBL, as well as the frequencies of nucleoplasmic bridges (NPB) and nuclear buds (NBUD) were higher in patients than in controls (Mann- Whitney test, p < 0.05). These results provide evidence that CBMN cytome assay in peripheral blood lymphocytes may be used to identify individuals who are at high risk of developing cervical cancer. Since the extent of DNA damage varies between CIN 2 and CIN 3, these findings support the CIN grading system.


Assuntos
Instabilidade Genômica/genética , Linfócitos/patologia , Lesões Intraepiteliais Escamosas/genética , Lesões Intraepiteliais Escamosas/patologia , Adulto , Idoso , Núcleo Celular/genética , Dano ao DNA/genética , Feminino , Humanos , Testes para Micronúcleos/métodos , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia
9.
Sci Total Environ ; 726: 138058, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32481203

RESUMO

External antiparasitic agents applied in bovine production represent a risk to consumers of meat products, especially if the conditions of their use are not strictly respected. The post-mortem control of residues in meat is an activity that must be updated and reinforced by the biomonitoring of live animals and the use of analytical tools to help identifying signs of early warning risks. The objective of the present study was to carry out a pre-slaughter biomonitoring approach in Aberdeen Angus cattle and crosses (n = 12) with the application of a commercial formulation of cypermethrin plus chlorpyrifos. This was performed with a single therapeutic dose applied on the backs of the cattle, through hematological, enzymatic, as well as hepatic and renal function analysis in plasma, and then quantifying the genotoxic effect on lymphocytes. Analytical measurements of plasma concentrations of cypermethrin plus chlorpyrifos at 24 h were negative and therefore a low absorption of the compounds was assumed. Measurement of acetyl cholinesterase showed no inhibition after exposure. The concentration of urea increased between 24 h and 168 h post application of the formulation, without showing any kidney damage. The rest of the parameters analyzed did not show any variations. This evaluation of hematological and biochemical effects and of cytokinesis-block micronucleus cytome assay in bovines is proposed as a pre-slaughter control of biomonitoring of the health status of animals, with a focus on food safety for meat consumers.


Assuntos
Clorpirifos , Piretrinas , Animais , Monitoramento Biológico , Bovinos , Dano ao DNA , Linfócitos , Testes para Micronúcleos
10.
Mutat Res ; 853: 503170, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32522350

RESUMO

We examined possible early-effect biomarkers and polymorphisms of susceptibility in primary school children living near the Atoyac River in central México, which receives waste from multiple industries. We observed a significant increase in micronucleated reticulocytes associated with the oxidative stress index (OSI) and the OGG1 GG (S326C) genotype, and a significant decrease of reticulocytes carrying the transferrin receptor, inversely correlated with OSI.


Assuntos
DNA Glicosilases/genética , Poluição Ambiental/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Polimorfismo Genético/efeitos dos fármacos , Reticulócitos/efeitos dos fármacos , Adolescente , Biomarcadores/metabolismo , Criança , Feminino , Genótipo , Humanos , Masculino , Testes para Micronúcleos/métodos
11.
Environ Sci Pollut Res Int ; 27(27): 33903-33915, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32535828

RESUMO

In this study, few different evaluation concepts were used for the assessment of genotoxic potential at the stretch of the Danube River identified as a significant hotspot of pollution originated through the untreated wastewaters. Three sites were chosen: one site upstream of the wastewater outlet in Novi Sad (Serbia), one at the outlet of wastewaters, and one site few kilometer downstream. Ex situ approach comprised prokaryotic SOS/umuC test on Salmonella typhimurium TA1535/pSK1005 and comet assay on human hepatoma cell line (HepG2). In situ approach was based on the active monitoring (cage approach) using freshwater mussels Sinanodonta woodiana and fish Cyprinus carpio. The comet and micronucleus assays were selected for evaluation of DNA damage in mussel haemocytes and fish blood cells. Within the ex situ part of the study, our results indicated that the eukaryotic model system is more sensitive compared to the prokaryotic one. In situ bioassays are recommended for obtaining a better insight into ecosystem status and in the case of our study the complete insight of genotoxic pressure. However, the choice of animals as bioindicators also has a significant impact on the quality of the obtained information. Differential response between fish and mussels was observed at the highly polluted site suggesting possible involvement of additional protective mechanism such as valve closure in mussels.


Assuntos
Carpas , Poluentes Químicos da Água , Animais , Bioensaio , Monitoramento Biológico , Ensaio Cometa , Dano ao DNA , Ecossistema , Monitoramento Ambiental , Humanos , Testes para Micronúcleos , Sérvia
12.
Environ Sci Pollut Res Int ; 27(26): 33215-33225, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32529609

RESUMO

Malachite green (MG) is a triphenylmethane dye that is widely used in aquaculture as a fungicide, bactericide, ectoparasiticide, and antiprotozoal. There is great debate regarding the potential for this compound to trigger adverse effects. Here, we review the previous findings and then evaluate the lethal and sublethal effects of MG in the species Hemichromis bimaculatus (jewelfish). The lethal concentration for 50% of the fish in 96 h was 1 mg/L. We observed a dose-dependent increase in the percentage of fish mortality as well as physical and behavioral changes. We further found that the highest tested sublethal dose significantly increased the DNA damage index identified using the comet assay (74.97 ± 13.8 at a significant level of P < 0.05 for the 0.75 mg/L concentration), but did not significantly alter the results of the micronucleus test. Although our results suggest that MG confers risks on exposed fish, the findings were significant only at the highest exposure concentration (0.75 mg/L). At lower concentrations (0.25 mg/L and 0.5 mg/L), no adverse effect was observed. The maximum MG concentration recommended for use in ornamental fish farming is 0.2 mg/L. Therefore, our results suggest that, specifically for the parameters analyzed in this work, MG does not have any adverse effect when users strictly adhere to the recommended concentration criteria for ornamental fish.


Assuntos
Brânquias , Poluentes Químicos da Água , Animais , Ensaio Cometa , Dano ao DNA , Testes para Micronúcleos , Corantes de Rosanilina
13.
Environ Sci Pollut Res Int ; 27(25): 31750-31759, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32504430

RESUMO

In the current study, we had two main purposes. Firstly, we aimed to compare genetic damages in the agricultural workers of two different types of environmental conditions including the greenhouse and open fields. Secondly, we aimed to compare genetic damages in the total agricultural workers as the exposed group (greenhouse and open field workers) (n = 114) and the non-exposed control group (n = 98) living in the same area in Canakkale, Turkey. For these purposes, we investigated the incidence of micronucleus (MN), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs) in peripheral blood lymphocytes. We observed that the frequencies of MN, NPB, and NBUD obtained for the greenhouse workers were statistically significantly higher than those obtained for the open field workers. When the results of the control group were compared with those of the total workers, there were statistically significant differences in terms of MN and NBUD frequencies. We found that age and MN were correlated at a significant level in both the agricultural workers and the control group. The MN frequency of the female workers was 1.5 times greater than that of the male workers, and it was a significant level in the agricultural workers.


Assuntos
Exposição Ocupacional/análise , Praguicidas , Agricultura , Dano ao DNA , Feminino , Humanos , Linfócitos , Masculino , Testes para Micronúcleos , Turquia
14.
J. nurs. health ; 10(2): 20102010, mai.2020.
Artigo em Português | LILACS, BDENF - Enfermagem | ID: biblio-1104139

RESUMO

Objetivo: analisar a produção científica acerca do teste de micronúcleo como instrumento para detecção de instabilidade genômica e dos fatores de risco para lesão intraepitelial cervical em pacientes com papilomavírus humano. Método: revisão integrativa de publicações dos últimos 10 anos, realizada no período de agosto de 2017 a junho de 2018, através da Medical Literature Analysis and Retrieval System, Literatura Latino-americana e do Caribe em Ciências da Saúde e PubMed Central. Resultados: quatro artigos foram analisados em que o teste de micronúcleo foi utilizado para detectar instabilidade genômica e risco de lesão intraepitelial cervical e seis artigos como biomarcador em diferentes estágios pré-neoplásicos, neoplásicos em lesões intraepiteliais e fatores de risco para o câncer cervical. Conclusões: o teste de micronúcleo é um método simples, rápido, barato e importante para detectar instabilidade genômica em células intraepiteliais cervicais que apresentam lesão sugestiva para o câncer de colo uterino.(AU)


Objective: to analyze the scientific production about the micronucleus test as an instrument for detecting genomic instability and risk factors for cervical intraepithelial injury in patients with human papillomavirus. Method: integrative review of publications from the last 10 years, carried out from August 2017 to June 2018, through Medical Literature Analysis and Retrieval System, Latin American and Caribbean Literature in Health Sciences and PubMed Central. Results: four articles were analyzed in which the micronucleus test was used to detect genomic instability and risk of cervical intraepithelial injury and in six articles as a biomarker in different pre-neoplastic stages, neoplastic in intraepithelial injuries and risk factors for cervical cancer. Conclusions: the micronucleus test is a simple, fast, inexpensive and important method to detect genomic instability in cervical intraepithelial cells that present lesions suggestive of cervical cancer.(AU)


Objetivo: analizar la producción científica sobre la prueba de micronúcleos como instrumento para detectar la inestabilidad genómica y los factores de riesgo de lesión intraepitelial cervical en pacientes con virus del papiloma humano. Método: revisión integradora de publicaciones de los últimos 10 años, realizada desde agosto de 2017 hasta junio de 2018, a través de la Medical Literature Analysis and Retrieval System, Literatura Latinoamericana y del Caribe en Ciencias de la Salud y PubMed Central. Resultados: se analizaron cuatro artículos en los que se utilizó la prueba de micronúcleos para detectar la inestabilidad genómica y el riesgo de lesión intraepitelial cervical y en seis artículos como biomarcador en diferentes etapas preneoplásicas, neoplásico en lesiones intraepiteliales y factores de riesgo de cáncer cervical. Conclusiones: la prueba de micronúcleos es un método simple, rápido, económico e importante para detectar la inestabilidad genómica en células intraepiteliales cervicales que presentan lesiones sugestivas de cáncer cervical.(AU)


Assuntos
Papillomaviridae , Neoplasias Uterinas , Testes para Micronúcleos
15.
Toxicology ; 441: 152474, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32380031

RESUMO

2-Methoxy-4-nitroaniline (MNA), an intermediate in the synthesis of azo dyes used in textiles and paints, is structurally similar to carcinogenic anilines. Human exposure occurs primarily in the occupational setting through handling of dye dust, and through use and disposal of MNA-containing products. MNA has been reported to induce contact hypersensitivity in a human, myocardial necrosis in rats, and bacterial mutagenicity. This study assessed the subacute toxicity, genotoxicity, contact hypersensitivity, and reproductive toxicity of MNA in rodents in an effort to more fully characterize its toxicological profile. B6C3F1/N mice were exposed to 0, 650, 1250, 2500, 5000, or 10,000 ppm MNA by dosed feed for 14-days to evaluate subacute toxicity and histopathological endpoints. In female mice, decreased body weight (13.5 %) and absolute kidney weight (14.8 %), compared to control, were observed at 10,000 ppm MNA; increased relative liver weight (10-12 %), compared to control, occurred at 5,000-10,000 ppm MNA. In male mice, absolute (15 %) and relative liver weights (9-13 %) were increased at 2,500-5,000 ppm and 1250-10,000 ppm MNA, compared to control, respectively. In both sexes of mice, minimal elevations of hemosiderin pigmentation (a breakdown product of erythrocytes), relative to control, were observed in the liver (10,000 ppm); minimal to moderate elevations of hemosiderin pigmentation (5,000-10,000 ppm) and minimal increases in hematopoietic cell proliferation occurred in the spleen (≥ 1250 ppm). In a reproductive toxicity study, timed-mated female Harlan Sprague Dawley rats were exposed to 0-10,000 ppm MNA by dosed feed from gestation day 6 through postnatal day (PND) 21. Decreases in mean litter weights were observed at 5000 ppm MNA, compared to control, beginning at PND1. To evaluate potential contact hypersensitivity, MNA (2.5-50 %, in dimethylformamide) was applied to the dorsa of both ears of female Balb/c mice once daily for three days. The increase observed in lymph node cell proliferation (10-50 % increase in thymidine uptake compared to control) did not reproducibly achieve the Sensitization Index (SI) 3 level, and there was no ear swelling evident following sensitization with 10-50 % MNA and challenge with 25 % MNA in the mouse ear swelling test. In bacterial mutagenicity assays, MNA (250-1000 µg/plate) induced significant increases, compared to control, in mutant colonies with and without metabolic activation enzymes in Salmonella typhimurium strains TA100 and TA98. These data indicate that MNA is genotoxic, and may induce erythrocyte damage and reactive phagocytosis by macrophages in the liver and spleen.


Assuntos
Compostos de Anilina/toxicidade , Dermatite de Contato/etiologia , Nitrocompostos/toxicidade , Reprodução/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Ensaio Cometa , Relação Dose-Resposta a Droga , Feminino , Fígado/efeitos dos fármacos , Linfonodos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Testes para Micronúcleos , Testes de Mutagenicidade , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
16.
Toxicol Lett ; 329: 80-84, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32360788

RESUMO

A large number of computer-based prediction methods to determine the potential of chemicals to induce mutations at the gene level has been developed over the last decades. Conversely, only few such methods are currently available to predict potential structural and numerical chromosome aberrations. Even fewer of these are based on the preferred testing method for this endpoint, i.e. the micronucleus test. For the present work, in vivo micronucleus test results of 718 structurally diverse compounds were collected and applied for the construction of new models by means of the freely available SARpy in silico model building software. Multiple QSAR models were created using parameter variation and manual verification of (non-) alerting structures. To this extent, the original set of 718 compounds was split into a training (80 %) and a test (20 %) set. SARpy was applied on the training set to automatically extract sets of rules by generating and selecting substructures based on their prediction performance whereas the test set was used to evaluate model performance. Five different splits were made randomly, each of which had a similar balance between positive and negative substances compared to the full dataset. All generated models were characterised by an overall better performance than existing free and commercial models for the same endpoint, while demonstrating high coverage.


Assuntos
Cromossomos/efeitos dos fármacos , Simulação por Computador , Bases de Dados de Ácidos Nucleicos , Testes para Micronúcleos , Modelos Biológicos , Relação Quantitativa Estrutura-Atividade , Animais , Sensibilidade e Especificidade , Software
17.
Environ Sci Pollut Res Int ; 27(22): 27626-27634, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32394259

RESUMO

The overall goal of the present study was to evaluate and compare the existence of genotoxic damage in Rattus norvegicus captured in sites with different levels of chemical mixtures along the Matanza-Riachuelo river basin (MRRB). For this, thirty-six wild rats (R. norvegicus) were captured from six different sites in the MRRB. Capture sites were characterized with concentrations of 20 parameters in surface water, including concentrations of metals and its soluble state and physicochemical parameters. To evaluate genotoxic damage in the rats, the bone marrow micronucleus test was performed. For this, the frequency of micronucleated polychromatic erythrocytes (MNPCE) was calculated based on the observation of 2000 polychromatic erythrocytes (PCE) per animal. Also, to detect possible cytotoxic effects, the PCE/TE (total erythrocytes) ratio in 1000 erythrocytes/animal was calculated. The frequency of MNPCE was positively associated with the highest concentration of chrome, lead, copper, biological oxygen demand, and chemical oxygen demand. Also, the decrease on PCE/TE ratio in bone marrow was related with increase of practically all metals and physicochemical parameters in surface water. The results of this study reveal that rats that live in the MRRB were exposed to concentrations of pollutants that can cause genotoxic damage, even though the concentrations of these pollutants are mostly below the safety standards. Therefore, this work highlights the importance of using methods that allow to integrate all environmental parameters in risk assessment, such as sentinel species.


Assuntos
Ecossistema , Rios , Animais , Argentina , Dano ao DNA , Eritrócitos , Testes para Micronúcleos , Ratos
18.
Mutat Res ; 850-851: 503133, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32247551

RESUMO

The "Micronuclei and Disease" workshop was organized by the HUMN Project consortium and hosted by the European Environmental Mutagen and Genomics Society at their annual meeting in Rennes, France, on 23 May 2019. The program of the workshop focused on addressing the emerging evidence linking micronucleus (MN) frequency to human disease. The first objective was to review what has been published and evaluate the level and quality of evidence for the connection between MN frequency and various diseases through all life stages. The second objective was to identify the knowledge gaps and what else needs to be done to determine the clinical utility of MN assays as predictors of disease risk and of prognosis when disease is active. Speakers at the workshop discussed the association of MN frequency with inflammation, infertility, pregnancy complications, obesity, diabetes, cardiovascular disease, kidney disease, cervical and bladder cancer, oral head and neck cancer, lung cancer, accelerated ageing syndromes, neurodegenerative diseases, and a road-map on how to utilise this knowledge was proposed. The outcomes of the workshop indicated that there are significant opportunities for translating the application of MN assays into clinical practice to improve disease prevention and risk management and to inform public health policy.


Assuntos
Dano ao DNA/efeitos dos fármacos , Metagenômica , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Mutagênicos/toxicidade , Humanos , Testes para Micronúcleos
19.
Mutat Res ; 850-851: 503135, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32247552

RESUMO

Use of three-dimensional (3D) tissue equivalents in toxicology has been increasing over the last decade as novel preclinical test systems and as alternatives to animal testing. In the area of genetic toxicology, progress has been made with establishing robust protocols for skin, airway (lung) and liver tissue equivalents. In light of these advancements, a "Use of 3D Tissues in Genotoxicity Testing" working group (WG) met at the 7th IWGT meeting in Tokyo in November 2017 to discuss progress with these models and how they may fit into a genotoxicity testing strategy. The workshop demonstrated that skin models have reached an advanced state of validation following over 10 years of development, while liver and airway model-based genotoxicity assays show promise but are at an early stage of development. Further effort in liver and airway model-based assays is needed to address the lack of coverage of the three main endpoints of genotoxicity (mutagenicity, clastogenicity and aneugenicity), and information on metabolic competence. The IWGT WG believes that the 3D skin comet and micronucleus assays are now sufficiently validated to undergo an independent peer review of the validation study, followed by development of individual OECD Test Guidelines.


Assuntos
Dano ao DNA/efeitos dos fármacos , Metagenômica/tendências , Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Dano ao DNA/genética , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Testes para Micronúcleos
20.
Mutat Res ; 850-851: 503143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32247554

RESUMO

BACKGROUND: The cytokinesis-block micronucleus (CBMN) assay is an internationally recognized method for measuring DNA damage after exposure to genotoxic agents, as well as a biomarker for DNA repair and chromosomal instability. The high baseline level of micronuclei (MN) in the healthy population has limited the sensitivity and application of the CBMN assay for the follow-up of exposed populations. We reevaluated the sensitivity of the CBNM assay using semi-automated MN scoring following telomere and centromere (TC) staining after in vitro exposure to genotoxic agents (mitomycin or radiation) or aneugenic agents (vinblastine). MATERIALS AND METHODS: Blood samples from 12 healthy donors were exposed to 137Cs at seven doses from 0.1-4 Gy and cultured for 72 h. Cytochalasin B was added at 46 h of culture. The exposure of chemical agents (mitomycin or vinblastine) was performed after 48 h of culture for 3 h. Cytochalasin B was added after treatment and slides were prepared 24 h after. MN was semi-automatically scored following TC staining. Nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) were assessed in a human cell line after TC staining. RESULTS: The introduction TC staining to the scoring of MN not only renders MN scoring more efficient and robust, but also permits discrimination between exposure to clastogenic (MN with only telomere signals) and aneugenic agents (MN with both TC signals). The resulting improvement of MN detection led to an increase in the sensitivity of the CBMN assay following low-dose radiation exposure (0.3 versus 0.1 Gy). Hyperradiosensitivity phenomenon was observed after low dose exposure. A dose-response curve was obtained for up to 4 Gy. In addition, TC staining permits assessment of the nature of NPBs and NBUDs as biomarkers for genotoxicity and chromosomal instability. CONCLUSION: These approaches can be potentially used to follow-up populations exposed to genotoxic agents and assess cancer risk.


Assuntos
Centrômero/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Testes de Mutagenicidade , Telômero/efeitos dos fármacos , Aneugênicos/farmacologia , Centrômero/genética , Citocinese/efeitos dos fármacos , Citocinese/genética , Dano ao DNA/genética , Humanos , Linfócitos/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Testes para Micronúcleos , Mutagênicos/toxicidade , Medição de Risco , Telômero/genética
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