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1.
Sci Total Environ ; 795: 148806, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34243001

RESUMO

Previous studies have demonstrated the presence of precursors and coupling agents in wastewater from hair dyeing processes. The complex reaction involved in the oxidation of these compounds can generate extremely hazardous sub-products, leading to an increase in the mutagenicity and toxicity of wastewater. Without proper treatment, this highly toxic wastewater may find its way into the drinking water treatment plant. The present work aimed to investigate the main products generated after the oxidation reaction involving p-toluenediamine (PTD) and p-aminophenol (PAP) - precursors that widely used in the composition of commercial permanent hair dyes, under experimental conditions close to the routine hair dyeing process (in the presence and absence of hydrogen peroxide in ammoniacal medium), using spectroscopic techniques. The study also investigated the mutagenicity and toxicity of the products formed in the hairdressing wash water and conducted detection analysis to determine the presence of the precursors and Bandrowski's Base Derivative (BBD) in samples of wastewater, surface and drinking water using HPLC-DAD and linear voltammetry techniques. Based on this investigation, we identified several PTD and PAP self-oxidation products and eleven sub-products derived from the reaction between PTD and PAP. Assays conducted using Salmonella typhimurium YG1041, with and without activation-induced rat liver metabolism (S9), indicated mutagenicity of the reaction products in concentrations above 10.0 µg µL-1. The concentrations of PTD, PAP, and several reactions and oxidation products of these precursors were detected in wastewater and water samples.


Assuntos
Tinturas para Cabelo , Aminofenóis , Animais , Tinturas para Cabelo/toxicidade , Testes de Mutagenicidade , Mutagênicos/toxicidade , Estresse Oxidativo , Fenilenodiaminas , Ratos
2.
Artigo em Inglês | MEDLINE | ID: mdl-34266624

RESUMO

The alkaline comet assay has been widely used to determine genotoxicity in human populations exposed to arsenic. The sample sizes of earlier studies were usually small, and inconsistent results were found. Meta-analyses can merge the results of multiple studies of the same type and increase the credibility of the conclusion by increasing the sample size. Thus, to investigate the monitoring effect of alkaline comet assay on genotoxicity for arsenic exposed population, meta-analyses were performed. Thirteen studies were found to meet the inclusion criteria and were included in this study; of them, twelve articles were of medium quality (15-20 points), only one study was of high quality (21-27 points). Meta-analyses showed that the overall estimates of Mean Ratio (MR, defined as the mean value of the response in the exposed group divided by that in the reference group) were 2.81(95 % confidence interval (CI) 1.93-4.10); 2.37(95 % CI, 1.73-3.26), and 1.69(95 %CI, 1.29-2.20) for comet tail length, % tail DNA, and tail moment, respectively. This shows that the level of DNA damage in arsenic exposed population is significantly higher than that in control populations. A meta-analysis of the correlation coefficients showed that the overall estimate was 0.52 (95 %CI, 0.48∼0.56, P<0.05) with all correlation coefficients included, but it changed to 0.24 (95 %CI, 0.17∼0.28, P<0.05) when two abnormal correlation coefficients were excluded, suggesting there was a positive correlation between arsenic load in vivo and DNA damage, but the overall estimate value of coefficients was unstable. Therefore, we conclude that the alkaline comet assay can be used as an effective genotoxic biomonitoring tool for arsenic-exposed populations. However, more and higher-quality studies are still needed to verify its actual application value.


Assuntos
Ensaio Cometa/métodos , Mutagênicos/toxicidade , Arsênio/toxicidade , DNA/metabolismo , Dano ao DNA , Humanos , Publicações
3.
Nutrients ; 13(6)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200310

RESUMO

Aspartame is a sweetener introduced to replace the commonly used sucrose. It was discovered by James M. Schlatter in 1965. Being 180-200 times sweeter than sucrose, its intake was expected to reduce obesity rates in developing countries and help those struggling with diabetes. It is mainly used as a sweetener for soft drinks, confectionery, and medicines. Despite its widespread use, its safety remains controversial. This narrative review investigates the existing literature on the use of aspartame and its possible effects on the human body to refine current knowledge. Taking to account that aspartame is a widely used artificial sweetener, it seems appropriate to continue research on safety. Studies mentioned in this article have produced very interesting results overall, the current review highlights the social problem of providing visible and detailed information about the presence of aspartame in products. The studies involving the impact of aspartame on obesity, diabetes mellitus, children and fetus, autism, neurodegeneration, phenylketonuria, allergies and skin problems, its cancer properties and its genotoxicity were analyzed. Further research should be conducted to ensure clear information about the impact of aspartame on health.


Assuntos
Aspartame/efeitos adversos , Aspartame/metabolismo , Alimentos , Humanos , Transtornos Mentais/induzido quimicamente , Mutagênicos/toxicidade , Degeneração Neural/induzido quimicamente , Preparações Farmacêuticas/análise
4.
Toxicology ; 459: 152859, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34273449

RESUMO

Vanadium dioxide nanoparticles (VO2 NPs) have been massively produced and widely applied due to their excellent metal-insulator transition property, making it extremely urgent to evaluate their safety, especially for low-dose long-term respiratory occupational exposure. Here, we report a comprehensive cytotoxicity and genotoxicity study on VO2 NPs to lung cell lines A549 and BEAS-2B following a long-term exposure. A commercial VO2 NP, S-VO2, was used to treat BEAS-2B (0.15-0.6 µg/mL) and A549 (0.3-1.2 µg/mL) cells for four exposure cycles, and each exposure cycle lasted for 4 consecutive days; then various bioassays were performed after each cycle. Significant proliferation inhibition was observed in both cell lines after long-term exposure of S-VO2 at low doses that did not cause apparent acute cytotoxicity; however, the genotoxicity of S-VO2, characterized by DNA damage and micronuclei, was only observed in A549 cells. These adverse effects of S-VO2 were exposure time-, dose- and cell-dependent, and closely related to the solubility of S-VO2. The oxidative stress in cells, i.e., enhanced reactive oxygen species (ROS) generation and suppressed reduced glutathione, was the main toxicity mechanism of S-VO2. The ROS-associated mitochondrial damage and DNA damage led to the genotoxicity, and cell proliferation retard, resulting in the cellular viability loss. Our results highlight the importance and urgent necessity of the investigation on the long-term toxicity of VO2 NPs.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Pulmão/patologia , Nanopartículas Metálicas/toxicidade , Mutagênicos/toxicidade , Óxidos/toxicidade , Compostos de Vanádio/toxicidade , Células A549 , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Dano ao DNA , Glutationa/metabolismo , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Testes para Micronúcleos , Estresse Oxidativo , Óxidos/farmacocinética , Espécies Reativas de Oxigênio/metabolismo , Compostos de Vanádio/farmacocinética
5.
Int J Mol Sci ; 22(12)2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34204826

RESUMO

Mexedrone, α-PVP and α-PHP are synthetic cathinones. They can be considered amphetamine-like substances with a stimulating effect. Actually, studies showing their impact on DNA are totally absent. Therefore, in order to fill this gap, aim of the present work was to evaluate their mutagenicity on TK6 cells. On the basis of cytotoxicity and cytostasis results, we selected the concentrations (35-100 µM) to be used in the further analysis. We used the micronucleus (MN) as indicator of genetic damage and analyzed the MNi frequency fold increase by flow cytometry. Mexedrone demonstrated its mutagenic potential contrary to the other two compounds; we then proceeded by repeating the analyzes in the presence of extrinsic metabolic activation in order to check if it was possible to totally exclude the mutagenic capacity for α-PVP and α-PHP. The results demonstrated instead the mutagenicity of their metabolites. We then evaluated reactive oxygen species (ROS) induction as a possible mechanism at the basis of the highlighted effects but the results did not show a statistically significant increase in ROS levels for any of the tested substances. Anyway, our outcomes emphasize the importance of mutagenicity evaluation for a complete assessment of the risk associated with synthetic cathinones exposure.


Assuntos
Alcaloides/toxicidade , Metanfetamina/análogos & derivados , Mutagênicos/toxicidade , Pentanonas/toxicidade , Pirrolidinas/toxicidade , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Metanfetamina/toxicidade , Micronúcleo Germinativo/efeitos dos fármacos , Micronúcleo Germinativo/metabolismo , Espécies Reativas de Oxigênio/metabolismo
6.
Appl Microbiol Biotechnol ; 105(13): 5607-5616, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34228183

RESUMO

Nitrosamine compounds, represented by N-nitrosodimethylamine, are regarded as potentially genotoxic impurities (PGIs) due to their hazard warning structure, which has attracted great attention of pharmaceutical companies and regulatory authorities. At present, great research gaps exist in genotoxicity assessment and carcinogenicity comparison of nitrosamine compounds. In this work, a collection of GFP-fused yeast cells representing DNA damage repair pathways were used to evaluate the genotoxicity of eight nitrosamine compounds (10-6-105 µg/mL). The high-resolution expression profiles of GFP-fused protein revealed the details of the DNA damage repair of nitrosamines. Studies have shown that nitrosamine compounds can cause extensive DNA damage and activate multiple repair pathways. The evaluation criteria based on the total expression level of protein show a good correlation with the mammalian carcinogenicity data TD50, and the yeast cell collection can be used as a potential reliable criterion for evaluating the carcinogenicity of compounds. The assay based on DNA damage pathway integration has high sensitivity and can be used as a supplementary method for the evaluation of trace PGIs in actual production. KEY POINTS: • The genotoxicity mechanism of nitrosamines was systematically studied. • The influence of compound structure on the efficacy of genotoxicity was explored. • GFP-fused yeast cells have the potential to evaluate impurities in production.


Assuntos
Técnicas Biossensoriais , Nitrosaminas , Animais , Dano ao DNA , Mutagênicos/toxicidade , Nitrosaminas/toxicidade , Saccharomyces cerevisiae/genética
7.
J Toxicol Environ Health A ; 84(19): 769-782, 2021 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-34176449

RESUMO

Kavain, kavalactone, present in Piper methysticum exhibits anticonvulsive, analgesic, anxiolytic, antiepileptic, antithrombotic, anti-inflammatory and antioxidant properties. Given its importance, the aim of the present study was to assess (1) the mutagenic and carcinogenicity of kavain administered alone and (2) the antimutagenic and anticarcinogenic potential when administered simultaneously with the chemotherapeutic drug doxorubicin (DXR) using the Somatic Mutation and Recombination Test (SMART) and Epithelial Tumor Test (ETT) using Drosophila melanogaster as a model system. Third-stage larvae from a standard (ST) and high metabolic bioactivation (HB) crosses were treated with different kavain concentrations (32, 64 or 128 µg/ml), alone or in conjunction with DXR (0.125 mg/ml). In ST descendants, kavain produced no significant mutagenic or recombinogenic effects. In the HB cross, mutagenic activity was observed at kavain concentrations of 64 and 128 µg/ml. In the DXR and kavain co-treatment, a modulating effect of the DXR-mediated mutagenic response dependent upon the concentration was detected in both crosses. In ETT, no marked carcinogenic or anticarcinogenic activity was noted for kavain. However, when kavain was combined with DXR synergistic induction of tumors by the chemotherapeutic drug occurred indicating that kavain enhanced the carcinogenic action of DXR.


Assuntos
Doxorrubicina/toxicidade , Drosophila melanogaster/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Pironas/farmacologia , Animais , Carcinogênese , Carcinógenos/toxicidade , Drosophila melanogaster/crescimento & desenvolvimento , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Testes de Mutagenicidade , Mutagênicos/toxicidade
8.
Methods Mol Biol ; 2326: 275-285, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34097276

RESUMO

The Ames assay is a classic and robust method for identifying and evaluating chemical mutagens that reverse the mutations of Salmonella typhimurium and/or Escherichia coli bacteria strains with amino acid synthesis defects. It is also called the bacterial reverse mutation assay. Ames assay has been widely used for detecting genetic toxicity of many chemicals and gained increased applications in risk assessment of emerging environmental pollutants such as nanomaterials. In this chapter, we presented a detailed step-by-step method using the Ames assay to detect potential mutagenicity of metal oxide nanoparticles. The strategy to use the liver S9 fraction for bioactivation and a preincubation procedure is recommended. This method is easy to use to test genetic toxicity of other environmental contaminants and new chemicals.


Assuntos
Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Nanopartículas/toxicidade , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Metais/toxicidade , Mutação/efeitos dos fármacos , Óxidos/toxicidade , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética
9.
Environ Sci Pollut Res Int ; 28(32): 43274-43286, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34189686

RESUMO

Dimethoate ([O,O-dimethyl S-(N-methylcarbamoylmethyl) phosphorodithioate]) is an organophosphate insecticide and acaricide widely used for agricultural purposes. Genotoxicity refers to the ability of a chemical agent interact directly to DNA or act indirectly leading to DNA damage by affecting spindle apparatus or enzymes involved in DNA replication, thereby causing mutations. Taking into consideration the importance of genotoxicity induced by dimethoate, the purpose of this manuscript was to provide a mini review regarding genotoxicity induced by dimethoate as a result of oxidative stress. The present study was conducted on studies available in MEDLINE, PUBMED, EMBASE, and Google scholar for all kind of articles (all publications published until May, 2020) using the following key words: dimethoate, omethoate, DNA damage, genetic damage, oxidative stress, genotoxicity, mutation, and mutagenicity. The results showed that many studies were published in the scientific literature; the approach was clearly demonstrated in multiple tissues and organs, but few papers were designed in humans. In summary, new studies within the field are important for better understanding the pathobiological events of genotoxicity on human cells, particularly to explain what cells and/or tissues are more sensitive to genotoxic insult induced by dimethoate.


Assuntos
Dimetoato , Inseticidas , Dano ao DNA , Dimetoato/toxicidade , Humanos , Inseticidas/toxicidade , Mutagênicos/toxicidade , Estresse Oxidativo
10.
Genes (Basel) ; 12(5)2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064921

RESUMO

In tomato (Solanum lycopersicum), there are at least three SlMLO (Mildew resistance Locus O) genes acting as susceptibility genes for the powdery mildew disease caused by Oidium neolycopersici, namely SlMLO1, SlMLO5 and SlMLO8. Of the three homologs, the SlMLO1 gene plays a major role since a natural mutant allele called ol-2 can almost completely prevent fungal penetration by formation of papillae. The ol-2 allele contains a 19-bp deletion in the coding sequence of the SlMLO1 gene, resulting in a premature stop codon within the second cytoplasmic loop of the predicted protein. In this study, we have developed a new genetic resource (M200) in the tomato cv. Micro-Tom genetic background by means of ethyl methane sulfonate (EMS) mutagenesis. The mutant M200 containing a novel allele (the m200 allele) of the tomato SlMLO1 gene showed profound resistance against powdery mildew with no fungal sporulation. Compared to the coding sequence of the SlMLO1 gene, the m200 allele carries a point mutation at T65A. The SNP results in a premature stop codon L22* located in the first transmembrane domain of the complete SlMLO1 protein. The length of the predicted protein is 21 amino acids, while the SlMLO1 full-length protein is 513 amino acids. A high-resolution melting (HRM) marker was developed to distinguish the mutated m200 allele from the SlMLO1 allele in backcross populations. The mutant allele conferred recessive resistance that was associated with papillae formation at fungal penetration sites of plant epidermal cells. A comprehensive list of known mlo mutations found in natural and artificial mutants is presented, which serves as a particularly valuable resource for powdery mildew resistance breeding.


Assuntos
Resistência à Doença , Lycopersicon esculentum/genética , Proteínas de Membrana/genética , Proteínas de Plantas/genética , Ascomicetos/patogenicidade , Metanossulfonato de Etila/toxicidade , Lycopersicon esculentum/microbiologia , Mutagênese , Mutagênicos/toxicidade , Mutação Puntual , Polimorfismo de Nucleotídeo Único
11.
Expert Opin Drug Metab Toxicol ; 17(8): 987-1005, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34078212

RESUMO

Introduction: Genotoxicity is an imperative component of the human health safety assessment of chemicals. Its secure forecast is of the utmost importance for all health prevention strategies and regulations.Areas covered: We surveyed several types of alternative, animal-free approaches ((quantitative) structure-activity relationship (Q)SAR, read-across, Adverse Outcome Pathway, Integrated Approaches to Testing and Assessment) for genotoxicity prediction within the needs of regulatory frameworks, putting special emphasis on data quality and uncertainties issues.Expert opinion: (Q)SAR models and read-across approaches for in vitro bacterial mutagenicity have sufficient reliability for use in prioritization processes, and as support in regulatory decisions in combination with other types of evidence. (Q)SARs and read-across methodologies for other genotoxicity endpoints need further improvements and should be applied with caution. It appears that there is still large room for improvement of genotoxicity prediction methods. Availability of well-curated high-quality databases, covering a broader chemical space, is one of the most important needs. Integration of in silico predictions with expert knowledge, weight-of-evidence-based assessment, and mechanistic understanding of genotoxicity pathways are other key points to be addressed for the generation of more accurate and trustable results.


Assuntos
Simulação por Computador , Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Alternativas aos Testes com Animais/métodos , Animais , Bases de Dados Factuais , Humanos , Relação Quantitativa Estrutura-Atividade , Reprodutibilidade dos Testes
12.
Nucleic Acids Res ; 49(11): 6331-6346, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-34096589

RESUMO

Cockayne syndrome (CS) is an autosomal recessive genetic disorder characterized by photosensitivity, developmental defects, neurological abnormalities, and premature aging. Mutations in CSA (ERCC8), CSB (ERCC6), XPB, XPD, XPG, XPF (ERCC4) and ERCC1 can give rise to clinical phenotypes resembling classic CS. Using a yeast two-hybrid (Y2H) screening approach, we identified LEO1 (Phe381-Ser568 region) as an interacting protein partner of full-length and C-terminal (Pro1010-Cys1493) CSB in two independent screens. LEO1 is a member of the RNA polymerase associated factor 1 complex (PAF1C) with roles in transcription elongation and chromatin modification. Supportive of the Y2H results, purified, recombinant LEO1 and CSB directly interact in vitro, and the two proteins exist in a common complex within human cells. In addition, fluorescently tagged LEO1 and CSB are both recruited to localized DNA damage sites in human cells. Cell fractionation experiments revealed a transcription-dependent, coordinated association of LEO1 and CSB to chromatin following either UVC irradiation or cisplatin treatment of HEK293T cells, whereas the response to menadione was distinct, suggesting that this collaboration occurs mainly in the context of bulky transcription-blocking lesions. Consistent with a coordinated interaction in DNA repair, LEO1 knockdown or knockout resulted in reduced CSB recruitment to chromatin, increased sensitivity to UVC light and cisplatin damage, and reduced RNA synthesis recovery and slower excision of cyclobutane pyrimidine dimers following UVC irradiation; the absence of CSB resulted in diminished LEO1 recruitment. Our data indicate a reciprocal communication between CSB and LEO1 in the context of transcription-associated DNA repair and RNA transcription recovery.


Assuntos
DNA Helicases/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Reparo do DNA , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Fatores de Transcrição/metabolismo , Cromatina/metabolismo , Adutos de DNA , Dano ao DNA , Células HEK293 , Células HeLa , Humanos , Mutagênicos/toxicidade , RNA/biossíntese , Fatores de Transcrição/química , Transcrição Genética
13.
Ecotoxicol Environ Saf ; 221: 112421, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34147865

RESUMO

A wide variety of organic micropollutants in drinking water pose a serious threat to human health. This study was aimed to reveal the characteristics of organic micropollution profiles in water from a drinking water treatment plant (DWTP) in the Yangtze River Delta, China and investigate the mutagenicity, health risk and disease burden through mixed exposure to micropollutants in water. The presence of organic micropollutants in seven categories in organic extracts (OEs) of water from the DWTP was determined, and Ames test was conducted to test the mutagenic effect of OEs. Meanwhile, health risk of exposure to organic micropollutants in finished water through three exposure routes (ingestion, dermal absorption and inhalation) was assessed with the method proposed by U.S. EPA, and disability-adjusted life years (DALYs) were combined to estimate the disease burden of cancer based on the carcinogenic risk (CR) assessment. The results showed that 28 organic micropollutants were detected in the raw and finished water at total concentrations of 967.28 ng/L and 1073.45 ng/L, respectively, of which phthalate esters (PAEs) were the dominant category (95.79% in the raw water and 96.61% in the finished water). Although the results of the Ames test for OEs were negative and the non-carcinogenic hazard index of the organic micropollutants in the finished water was less than 1 in all age groups, the total CR was 2.17 × 10-5, higher than the negligible risk level (1.00 × 10-6). The total DALYs caused by the organic micropollutants in the finished water was 2945.59 person-years, and the average individual DALYs was 2.21 × 10-6 per person-year (ppy), which was 2.21 times the reference risk level (1.00 × 10-6 ppy) defined by the WHO. Exposure to nitrosamines (NAms) was the major contributor to the total CR (92.06%) and average individual DALYs (94.58%). This study demonstrated that despite the negative result of the mutagenicity test with TA98 and TA100 strains, the health risk of exposure to organic micropollutants in drinking water should not be neglected.


Assuntos
Água Potável/análise , Mutagênicos/análise , Compostos Orgânicos/análise , Poluentes Químicos da Água/análise , China , Efeitos Psicossociais da Doença , Monitoramento Ambiental , Humanos , Testes de Mutagenicidade , Mutagênicos/toxicidade , Compostos Orgânicos/toxicidade , Medição de Risco , Rios , Poluentes Químicos da Água/toxicidade , Purificação da Água
15.
Toxins (Basel) ; 13(5)2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-34065799

RESUMO

Colibactin is a secondary metabolite encoded by the pks gene island identified in several Enterobacteriaceae, including some pathogenic Escherichia coli (E. coli) commonly enriched in mucosal tissue collected from patients with inflammatory bowel disease and colorectal cancer. E. coli harboring this biosynthetic gene cluster cause DNA damage and tumorigenesis in cell lines and pre-clinical models, yet fundamental knowledge regarding colibactin function is lacking. To accurately assess the role of pks+ E. coli in cancer etiology, the biological mechanisms governing production and delivery of colibactin by these bacteria must be elucidated. In this review, we will focus on recent advances in our understanding of colibactin's structural mode-of-action and mutagenic potential with consideration for how this activity may be regulated by physiologic conditions within the intestine.


Assuntos
Enterobacteriaceae/metabolismo , Mutagênicos/metabolismo , Peptídeos/metabolismo , Policetídeos/metabolismo , Animais , Dano ao DNA , Enterobacteriaceae/genética , Humanos , Família Multigênica , Mutagênicos/toxicidade , Peptídeos/toxicidade , Policetídeos/toxicidade , Metabolismo Secundário
16.
Artigo em Inglês | MEDLINE | ID: mdl-34067860

RESUMO

The aim of this paper was to investigate the relationship between micronuclei and DNA damage in children's buccal mucosa cells and the genotoxicity and mutagenicity of the different sized fractions of particulate matter as well as the concentration of PAHs (polycyclic aromatic hydrocarbons) and metals in particulate matter. Air particulate matter was collected by high volume samplers located near the schools attended by the children on the same days of biological samplings. The mutagenic activity was assessed in different cells in in vitro tests (Ames test on bacteria and comet test on leukocytes). Our study showed weak positive correlations between (a) the mutagenicity of the PM0.5 fraction and PAHs and (b) the micronuclei test of children's buccal cells and PAHs detected in PM0.5 and PM0.5-3 fractions. A positive correlation was also found between in vitro comet test on leukocytes and PAHs in the PM3-10 fraction. No correlation was observed for metal concentrations in each PM fraction.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Criança , Dano ao DNA , Humanos , Mucosa Bucal , Testes de Mutagenicidade , Mutagênicos/toxicidade , Material Particulado/análise , Material Particulado/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidade
17.
Int J Mol Sci ; 22(10)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34070033

RESUMO

Drought response in wheat is considered a highly complex process, since it is a multigenic trait; nevertheless, breeding programs are continuously searching for new wheat varieties with characteristics for drought tolerance. In a previous study, we demonstrated the effectiveness of a mutant known as RYNO3936 that could survive 14 days without water. In this study, we reveal another mutant known as BIG8-1 that can endure severe water deficit stress (21 days without water) with superior drought response characteristics. Phenotypically, the mutant plants had broader leaves, including a densely packed fibrous root architecture that was not visible in the WT parent plants. During mild (day 7) drought stress, the mutant could maintain its relative water content, chlorophyll content, maximum quantum yield of PSII (Fv/Fm) and stomatal conductance, with no phenotypic symptoms such as wilting or senescence despite a decrease in soil moisture content. It was only during moderate (day 14) and severe (day 21) water deficit stress that a decline in those variables was evident. Furthermore, the mutant plants also displayed a unique preservation of metabolic activity, which was confirmed by assessing the accumulation of free amino acids and increase of antioxidative enzymes (peroxidases and glutathione S-transferase). Proteome reshuffling was also observed, allowing slow degradation of essential proteins such as RuBisCO during water deficit stress. The LC-MS/MS data revealed a high abundance of proteins involved in energy and photosynthesis under well-watered conditions, particularly Serpin-Z2A and Z2B, SGT1 and Calnexin-like protein. However, after 21 days of water stress, the mutants expressed ABC transporter permeases and xylanase inhibitor protein, which are involved in the transport of amino acids and protecting cells, respectively. This study characterizes a new mutant BIG8-1 with drought-tolerant characteristics suited for breeding programs.


Assuntos
Secas , Mutação , Triticum/genética , Triticum/fisiologia , Aclimatação/genética , Aminoácidos/metabolismo , Antioxidantes/metabolismo , Clorofila/metabolismo , Metanossulfonato de Etila/toxicidade , Mutagênicos/toxicidade , Fenótipo , Complexo de Proteína do Fotossistema II/metabolismo , Melhoramento Vegetal , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Proteoma/metabolismo , Ribulose-Bifosfato Carboxilase/metabolismo , Estresse Fisiológico/genética , Triticum/efeitos dos fármacos , Água/metabolismo
18.
J Toxicol Environ Health A ; 84(17): 689-701, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34034641

RESUMO

Nicotiana tabacum is the most cultivated tobacco species in the state of Rio Grande do Sul, Brazil. Workers who handle the plant are exposed to the leaf components during the harvesting process and when separating and classifying the dried leaves. In addition to nicotine, after the drying process, other components may be found including tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, as well as pesticides residues. The objective of this study was to examine the genotoxicity attributed to the aqueous extract of dried tobacco leaves obtained from tobacco barns using Chinese hamster lung fibroblast cells (V79) as a model system by employing alkaline comet assay, micronucleus (MN) and Ames test. MTT assay was used to assess cytotoxicity and establish concentrations for this study. Data demonstrated cell viability > 85% for concentrations of 0.625-5 mg/ml while the comet assay indicated a significant increase in DNA damage at all concentrations tested. A significant elevation of MN and nuclear buds (NBUD) was found for 5 mg/ml compared to control and other dry tobacco leaves concentrations (0.625-2.5 mg/ml). Mutagenicity was not found using the Salmonella/Microsome test (TA98, TA100, and TA102 strains) with and without metabolic activation. The concentration of inorganic elements was determined employing the PIXE technique, and 13 inorganic elements were detected. Using CG/MS nicotine amounts present were 1.56 mg/g dry tobacco leaf powder. Due to the observed genotoxicity in V79 cells, more investigations are needed to protect the health of tobacco workers exposed daily to this complex mixture of toxic substances present in dry tobacco leaves.


Assuntos
Mutagênicos/toxicidade , Folhas de Planta/química , Tabaco/química , Animais , Linhagem Celular , Ensaio Cometa , Cricetulus , Testes para Micronúcleos , Testes de Mutagenicidade
19.
J Toxicol Environ Health A ; 84(15): 632-648, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-33970833

RESUMO

Rovral® is a fungicide used to control pests that affect various crops and little is known regarding its effects on embryonic development of amniotes. Thus, this study aimed to determine the influence of Rovral® during chicken organogenesis using acute in ovo contamination. Fertilized eggs were inoculated with different concentrations of Rovral® (100, 300, 500 or 750 µl/ml), injected into the egg's air chamber. After 7 days, embryos were examined for possible malformations, staging, weight and mortality. Subsequently, head, trunk, limbs and eyes were measured for morphometry and asymmetry. For blood analysis, eggs were treated with 300 µl/ml Rovral® and glucose, presence of micronuclei and erythrocyte nuclei abnormalities determined. Treatments with Rovral® affected the mortality rate in a concentration-dependent manner. LC50 value was found to be 596 µl/ml which represents 397-fold higher than the recommended concentration for use. Rovral® produced several malformations including hemorrhagic, ocular and cephalic abnormalities. No significant changes were observed in body weight, staging, body measurements, symmetry and glucose levels of live embryos, which indicates this fungicide presents low toxicity under the analyzed conditions. Changes in erythrocyte nuclei were noted; however significant difference was observed only for presence of binucleated erythrocytes. It is important to point out that possibly more significant changes may have occurred at lower concentrations through chronic contamination. Therefore, caution is needed in the use of this fungicide, since it presents teratogenic and mutagenic potential.


Assuntos
Aminoimidazol Carboxamida/análogos & derivados , Embrião de Galinha/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Hidantoínas/toxicidade , Aminoimidazol Carboxamida/toxicidade , Animais , Galinhas , Relação Dose-Resposta a Droga , Dose Letal Mediana , Mutagênicos/toxicidade , Teratógenos/toxicidade
20.
Chem Biol Interact ; 345: 109531, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34058178

RESUMO

Genotoxicity has been identified as the main cause of infertility and a variety of cancers. The mechanisms affect the structure, quality of the information or the segregation of DNA and are not inherently correlated with mutagenicity. The concept of genotoxicity, the chemical classes that cause genetic damage and the associated mechanisms of action are discussed here. Hazardous effects of pharmaceuticals, cosmetics, agrochemicals, industrial compounds, food additives, natural toxins and nanomaterials are, in large part, identified by genotoxicity and mutagenicity tests. These are critical and early steps in industrial and regulatory health assessment. Though several in vitro experiments are commonly used and approval by regulatory agencies for commercial licensing of drugs, their accuracy in human predictions for genotoxic and mutagenic effects is frequently questioned. Treatment of real and functional genetic toxicity problems depends in detail on the knowledge of mechanisms of DNA damage in the molecular, subcellular, cellular and tissue or organ system levels. Current strategies for risk assessment of human health need revisions to achieve robust and reliable results for optimizing their effectiveness. Additionally, computerized methods, neo-biomarkers leveraging '-omics' approaches, all of which can provide a convincing genotoxicity evaluation to reduce infertility and cancer risk.


Assuntos
Infertilidade/induzido quimicamente , Infertilidade/genética , Mutagênicos/toxicidade , Neoplasias/induzido quimicamente , Neoplasias/genética , Animais , Humanos , Medição de Risco
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