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1.
An Acad Bras Cienc ; 91(3): e20180655, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576914

RESUMO

This study evaluated 24 patients with lung cancer (CA) and 23 individuals with no smoking history or cancer in the family and without respiratory disease in childhood (CO). Peripheral blood lymphocytes was used to perform alkaline comet assay and to assess DNA damage as well as to evaluate methyl methane sulfonate (MMS) DNA repair after one hour and three hours at 37 ºC. The percentage of residual damage (RD) after three hours of MMS treatment, for each patient was assessed. The majority of patients were in the CA group, male patients, former smokers, with a history of smoking for 15 years and without associated comorbidities. Alkaline and residual damages were higher in the CA group when compared to controls (alkaline damage P = 0.015 and RD P = 0.05). After one hour of MMS treatment the DNA damage of the CA increased indicating failure to repair it, compared to the controls, and after three hours DNA repair was observed in both groups. Patients with lung cancer are mostly men, former smokers and with more than 15 years of tobacco consumption, undergoing chemotherapy, have high rates of DNA damage and deficiency in their ability to repair against induced damage when compared to controls.


Assuntos
Dano ao DNA , Reparo do DNA , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Idoso , Antineoplásicos Alquilantes/farmacologia , Estudos de Casos e Controles , Ensaio Cometa/métodos , Estudos Transversais , Feminino , Humanos , Linfócitos/efeitos dos fármacos , Masculino , Metanossulfonato de Metila/farmacologia , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fumar/efeitos adversos , Fatores de Tempo
2.
Medicine (Baltimore) ; 98(32): e16518, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393354

RESUMO

BACKGROUND: The main objective was to evaluate and compare the local genotoxicity of sevoflurane and desflurane in bronchoalveolar cells, while the secondary outcome was to detect systemic oxidative DNA damage. To our knowledge, our study is the first one to evaluate the local effects of inhalation anesthetics in human bronchoalveolar cells in patients. METHODS: American Society of Anesthesiologists group I-II patients scheduled for lumbar discectomy surgery were enrolled in this randomized prospective study. Patients were randomized to sevoflurane or desflurane for anesthesia maintenance. Bronchoalveolar lavage samples and peripheral blood samples were taken at 2-time points: the first point (baseline, T1); and the second point (postexposure, T2). Final number of 48 samples were the sevoflurane (n = 22) and desflurane (n = 26) groups. Comet assay was applied to examine genotoxic properties. Oxidative DNA damage in plasma was measured with 8-hydroxy-2'-deoxyguanosine (8-OHdG). RESULTS: T2 values were higher than baseline values in both the desflurane group (tail-length: 66 ±â€Š24, %DNA in tail: 72 ±â€Š60, tail moment: 47.52 ±â€Š14.4; P = .001, P = .005, P = .001, respectively) and the sevoflurane group (tail-length: 58 ±â€Š33, %DNA in tail: 88 ±â€Š80, tail moment: 51.04 ±â€Š26.4; P = .001, P = .012, P = .001, respectively). T2 plasma 8-OHdG levels were also higher than baseline levels in the desflurane group (3.91 ±â€Š0.19 ng/ml vs 1.32 ±â€Š0.20 ng/ml, P = .001) and sevoflurane group (3.98 ±â€Š0.18 ng/ml vs 1.31 ±â€Š0.11 ng/ml, P = .001). There were no differences between the 2 groups in comet parameters and 8-OHdG levels. CONCLUSION: Our results indicate that both inhalation agents cause DNA damage in the bronchoalveolar cells. Also, we detected increases in plasma 8-OHdG concentrations. Local genotoxicity and systemic oxidized DNA damage were similar in both groups.


Assuntos
Anestésicos Inalatórios/efeitos adversos , Anestésicos Inalatórios/farmacologia , Líquido da Lavagem Broncoalveolar/citologia , Dano ao DNA/efeitos dos fármacos , Adulto , Idoso , Ensaio Cometa , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangue , Desflurano/efeitos adversos , Desflurano/farmacologia , Discotomia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Estudos Prospectivos , Sevoflurano/administração & dosagem , Sevoflurano/farmacologia
3.
Niger J Clin Pract ; 22(8): 1041-1048, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31417045

RESUMO

Background: X-rays are potential mutagenic agents that can cause both the gene mutations and chromosomal aberrations. Aims: In this study, the micronucleus (MN) test and the comet assay methods are implemented in order to observe the damage that can occur in the cell nucleus and in the structure of DNA of the patients who underwent a panoramic examination. Methods and Materials: In our study, buccal mucosa swabs were obtained just before the radiography and 2 weeks after the radiography from 30 volunteer patients who had to take radiographs due to dental diagnosis. Changes in the nuclei of 1,000 cells of each swab sample had been counted under a light microscope and recorded. Besides, 100 cells of each other swab samples were analyzed by the comet assay. Comet assay parameters namely tail length and percentage of DNA in tail, which indicate the level of DNA damage were analyzed and compared in both groups. Statistical analysis was performed by using the Statistical Package for the Social Sciences (Version 21). Results: In our study, the results of percentage of DNA in tail and tail length before and after X-ray exposure were statistically significant (P < 0.001). Likewise, increase in the MN frequency observed in buccal mucosa cells after X-ray exposure was found significant (P < 0.001). Conclusions: As a result, panoramic radiographs taken during dental diagnosis and treatment cause cytotoxicity and DNA damage in oral mucosal cells. Panoramic radiographs should be applied only when necessary, using an accurate radiographic technique and radioprotection criteria.


Assuntos
Núcleo Celular/efeitos da radiação , Dano ao DNA/efeitos da radiação , Mucosa Bucal/efeitos da radiação , Radiografia Panorâmica/efeitos adversos , Ensaio Cometa , Feminino , Humanos , Masculino , Testes para Micronúcleos , Mucosa Bucal/citologia , Testes de Mutagenicidade
4.
Anticancer Res ; 39(8): 4011-4017, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366482

RESUMO

BACKGROUND/AIM: Genotoxicity is the capacity of an agent to induce damage to DNA. Given the close relationship between genotoxicity and carcinogenesis, several assays have been developed for detecting genetic damage. Among them, the single-cell gel (comet) assay plays an important role for evaluating DNA damage in mammalian cells, including those of the oral cavity. The purpose of this article was to provide a critical review of the application of single-cell gel comet assay to buccal cells. MATERIAL AND METHODS: A search of the scientific literature was conducted of published studies available on single-cell gel comet assay and oral cells. RESULTS: The results showed that the majority of studies were conducted on humans, whereas few were designed for use in rodents and in vitro. CONCLUSION: Further studies within the field are relevant for better understanding the underlying mechanisms of genotoxicity in oral cells, especially since the use of humans is quite complicated due to issues of ethics.


Assuntos
Carcinogênese/genética , Dano ao DNA/genética , Boca/efeitos dos fármacos , Análise de Célula Única/métodos , Ensaio Cometa/métodos , DNA/genética , Humanos , Boca/patologia , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Mutagênicos
5.
Sci Total Environ ; 691: 605-610, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31325860

RESUMO

The potential for bioaccumulation and associated genotoxicity of nonextractable residues (NERs) of polycyclic aromatic hydrocarbon (PAHs) in long-term contaminated soils have not been investigated. Here we report research in which earthworms, Eisenia fetida, were exposed to a soil containing readily available benzo[a]pyrene (B[a]P) and highly sequestered B[a]P NERs aged in soil for 350 days. B[a]P bioaccumulation was assessed and DNA damage (as DNA single strand breaks) in earthworm coelomocytes were evaluated by comet assay. The concentrations of B[a]P in earthworm tissues were generally low, particularly when the soil contained highly sequestered B[a]P NERs, with biota-soil accumulation factors ranging from 0.6 to 0.8 kgOC/kglipid. The measurements related to genotoxicity, that is percentage (%) of DNA in the tails and olive tail moments, were significantly greater (p < 0.05) in the spiked soil containing readily available B[a]P than in soil that did not have added B[a]P. For example, for the soil initially spiked at 10 mg/kg, the percentage of DNA in the tails (29.2%) of coelomocytes after exposure of earthworms to B[a]P-contaminated soils and olive tail moments (17.6) were significantly greater (p < 0.05) than those of unspiked soils (19.6% and 7.0, for percentage of DNA in tail and olive tail moment, respectively). There were no significant (p > 0.05) differences in effects over the range of B[a]P concentrations (10 and 50 mg/kg soil) investigated. In contrast, DNA damage after exposure of earthworms to B[a]P NERs in soil did not differ from background DNA damage in the unspiked soil. These findings are useful in risk assessments as they can be applied to minimise uncertainties associated with the ecological health risks from exposure to highly sequestered PAH residues in long-term contaminated soils.


Assuntos
Benzo(a)pireno/toxicidade , Oligoquetos/fisiologia , Poluentes do Solo/toxicidade , Animais , Benzo(a)pireno/metabolismo , Ensaio Cometa , Dano ao DNA , Poluentes do Solo/metabolismo
6.
Mem Inst Oswaldo Cruz ; 114: e190017, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31271593

RESUMO

BACKGROUND: Only benznidazole (Bnz) (1) and nifurtimox (Nfx) (2) are licensed for the treatment of Chagas disease although their safety and efficacy profile are far from ideal. Farmanguinhos from Fiocruz has developed seven nitroimidazole compounds (4-10) analogs of megazol (3). OBJECTIVES: To evaluate whether the genotoxic effect of 3 was abolished in the seven nitroimidazoles (4-10) analogs using the in vitro alkaline comet assay (CA) and the in vitro cytokinesis-block micronucleus assay (CBMN) in whole human blood cells (WHBC) and correlate this effect with their trypanocidal activity using bloodstream trypomastigote forms of Trypanosoma cruzi. METHODS: The toxicity of 3-10 to WHBC in the in vitro CA was determined using the fluorescein diacetate/ethidium bromide assay. DNA damage in the in vitro CA was evaluated according to tail size in four classes (0-3) and methyl methane-sulfonate (MMS) was used as a positive control. The cytotoxicity of 3-10 to WHBC in the CBMN was measured using the cytokinesis-block proliferation index and the replication index. The number of the micronucleate cells in 2,000 binucleate cells by experimental group was determined. Mitomycin C and N-deacetyl-N-methylcolchicine were used as positive controls. FINDINGS: Compound 3 showed a significant DNA strand break effect through the in vitro CA and highly significant clastogenic and/or aneugenic effect in the CBMN. Compounds 5, 6, 8, 9 and 10 showed negative results in the CBMN and positive results in the in vitro CA, while the inverse effect was observed for 4 and 7. MAIN CONCLUSIONS: Compound 10 was the most promising to proceed with the development as a drug candidate in the treatment of Chagas disease showing absence of chromosomal cytogenetic damage and high activity against T. cruzi, about two times higher than 3 and the clinical drug 1.


Assuntos
Nitroimidazóis/toxicidade , Tripanossomicidas/toxicidade , Células Sanguíneas/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa/métodos , Dano ao DNA , Humanos , Testes para Micronúcleos/métodos , Nifurtimox/química , Nifurtimox/toxicidade , Nitroimidazóis/química , Valores de Referência , Reprodutibilidade dos Testes , Tiadiazóis/química , Tiadiazóis/toxicidade , Fatores de Tempo , Tripanossomicidas/química , Trypanosoma cruzi/efeitos dos fármacos
7.
J Agric Food Chem ; 67(31): 8668-8676, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31271028

RESUMO

This study investigated the effect of Chlorella vulgaris (C. vulgaris) on genotoxicity, cytotoxicity, and apoptosis in Caco-2 and HT-29 cells. C. vulgaris significantly induced DNA damage in both cell lines at a concentration of 200 µg dry matter/mL (comet tail intensity CTI: 24.6 ± 4.7% for Caco-2, 16.6 ± 0.9% for HT-29). The application of processing (sonication, ball-milling) did not affect the genotoxicity negatively and lowered the lipid peroxidation in C. vulgaris preparations. C. vulgaris-induced intracellular formation of reactive oxygen species in human cell lines and might be responsible for the genotoxic effect. A solid fraction mainly triggered the observed DNA damage (CTI: 41.5 ± 1.9%), whereas a hydrophilic (CTI: 7.9 ± 1.7%) and lipophilic (CTI: 10.2 ± 2.1%) fraction revealed a significantly lower tail intensity. C. vulgaris significantly induced DNA damage in both cell lines possibly through intracellular formation of reactive oxygen species; however, it was repaired after a 2 h recovery time or was even avoided at lower concentrations. In addition, none of the preparations indicated an adverse effect on cell proliferation or revealed apoptotic activity.


Assuntos
Chlorella vulgaris/química , Dano ao DNA/efeitos dos fármacos , Células Epiteliais/citologia , Mutagênicos/toxicidade , Extratos Vegetais/toxicidade , Apoptose/efeitos dos fármacos , Processos Autotróficos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Chlorella vulgaris/crescimento & desenvolvimento , Chlorella vulgaris/efeitos da radiação , Ensaio Cometa , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Luz , Peroxidação de Lipídeos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
8.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(2): 97-100, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-31250598

RESUMO

OBJECTIVE: To clarify the genotoxicity induced by acute exposure of ozone with different concentrations on pulmonary cells in rats. METHODS: Thirty-six Wistar rats were randomly divided into control group (filtered air exposure) and ozone exposure group (0.12 ppm, 0.5 ppm, 1.0 ppm, 2.0 ppm, 4.0 ppm) with 6 in each group. After rats were exposed to different concentrations of ozone for 4 h, lung tissues were taken and single cells were isolated. Then, 8-hydroxydeoxyguanosine (8-OHdG) was quantitatively detected by enzyme-linked immunosorbent assay. Comet assay, micronucleus test and DNA- protein cross-linking assay were used to analyze DNA and chromosome damages. RESULTS: Compared with the control group, the content of 8-OHdG in lung tissue was increased significantly from the ozone exposure concentration of 0.12 ppm, reaching the highest value at 0.5 ppm. With the increase of ozone exposure concentration, the tail rate of comets was increased gradually, and there was a significant dose-effect relationship. The cross-linking rate of DNA- protein was increased first and then was decreased with a maximum value at 2.0 ppm group. Although the micronucleus rate of lung cells showed an upward trend, there was no significant difference compared with the control group. CONCLUSION: Acute exposure of ozone at low concentrations (0.12 ppm) could lead to DNA damage in the pulmonary cells of rats, while no significant chromosome damage was found even in the group with ozone concentration reached to 4 ppm.


Assuntos
Dano ao DNA , Pulmão/patologia , Ozônio/efeitos adversos , Animais , Ensaio Cometa , Pulmão/citologia , Testes para Micronúcleos , Distribuição Aleatória , Ratos , Ratos Wistar
9.
Arch Environ Contam Toxicol ; 77(3): 409-420, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31236619

RESUMO

Amphibians are constantly exposed to pollutants and the stress of agricultural activities. We selected three anuran amphibian species Dendropsophus minutus, Boana albopunctata, and Physalaemus cuvieri, totaling 309 individuals. We collected tadpoles in 15 permanent ponds: 5 soybean crops, 3 corn crops, and 7 nonagricultural lands. Our study provides the first comparative data on the genotoxicity and mutagenicity of three common amphibian anurans. Dendropsophus minutus was the most vulnerable species compared with B. albopunctata and P. cuvieri for comet assay and micronuclei test. However, the more significant amount of DNA damage seen in D. minutus does not mean that their populations are threatened once such species adapt well to anthropogenic disturbances. Despite, P. cuvieri was less sensitive than the other two species; the DNA damage was significantly higher in soybean crops. Physalaemus cuvieri is a leptodactylidae species that deposit their eggs in foam nests, which are essential to protect eggs from dehydration. Moreover, the foam reduces the contact of eggs with water; thus, P. cuvieri eggs could be less exposed to contaminants present in pounds, compared with D. minutus and B. albopunctata, which deposit their eggs directly in the water. Therefore, this study was sufficiently sensitive to detect genotoxic and mutagenic effects in tadpoles exposed to agroecosystems. We strongly suggest D. minutus in future biomonitoring studies that involve the comparison of anthropized versus not anthropized environments. Overall, we recommend the comet assay and micronucleus test as effective methods for the detection of genotoxic damage in amphibian anurans to the environmental disturbance, especially in agricultural sites.


Assuntos
Anuros/genética , Ensaio Cometa/métodos , Testes para Micronúcleos/métodos , Agricultura , Animais , Brasil , Dano ao DNA/efeitos dos fármacos , Ecossistema , Ecotoxicologia/métodos , Monitoramento Ambiental/métodos , Larva/efeitos dos fármacos , Larva/genética , Tanques , Soja , Poluentes Químicos da Água/toxicidade , Zea mays
10.
Environ Pollut ; 252(Pt A): 917-923, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31226516

RESUMO

Glyphosate-based herbicides (GBH) are the most widely used pesticides in the world. The extensive use of them increases the potential human health risk, including the human inhalation toxicity risk. We studied the effect of the most famous GBH Roundup® (RDP) in the concentration range from 50 to 125 µg/mL on Mitochondria-Associated apoptosis and DNA damage in Human alveolar carcinoma cells (A549 cells). Alkaline comet assay, immunofluorescence assay and Flow Cytometric Analysis assay were employed to detect DNA damages and apoptosis of A549 cells. We found RDP caused concentration-dependent increases in DNA damages and proportion of apoptotic cells in A549 cells. RDP induced the DNA single-strand breaks and double-strand breaks; the collapse of mitochondrial membrane by increasing Bax/Bcl-2, resulting in the release of cytochrome c into cytosol and then activated caspase-9/-3, cleaved poly (ADP-ribose) polymerase (PARP) in human lung tissue cells. The results demonstrate that RDP can induce A549 cells cytotoxic effects in vitro at the concentration lower than the occupational exposures level of workers, which means RDP has a potential threat to human health.


Assuntos
Apoptose/efeitos dos fármacos , Glicina/análogos & derivados , Herbicidas/toxicidade , Pulmão/patologia , Mitocôndrias/efeitos dos fármacos , Células A549 , Adenocarcinoma Bronquioloalveolar/genética , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Ensaio Cometa , Citocromos c/metabolismo , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Quebras de DNA de Cadeia Simples/efeitos dos fármacos , Glicina/toxicidade , Humanos , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo
11.
J Food Sci ; 84(7): 1979-1985, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31206673

RESUMO

Essential oils (EO) are widely used in foods as flavoring and preservative agents. Many of the biological activities of EO have been attributed to major essential oil compounds (EOC) but their direct interaction with colonic epithelial cells and their genotoxic and genoprotective effects are not well established. In this study, the cytotoxicity and genotoxicity of EOC including nerolidol, thymol, geraniol, methylisoeugenol, eugenol, linalool, and a commercial blend (Agolin) were determined. Furthermore, the genoprotective effects of EOC against oxidative and methylating damage were assessed using the comet assay in HT-29 colorectal adenocarcinoma cells. The majority of EOC were cytotoxic to HT-29 cells at or above 250 ppm after 24 hr exposure. At noncytotoxic doses, none of the EOC was genotoxic in the comet assay. Genoprotection against oxidative DNA damage was observed for nerolidol (at 62.5 ppm), thymol (at 12.5 ppm), geraniol, and methylisoeugenol (both at 125 ppm), as well as linalool and Agolin (both at 250 ppm). Thymol was the most protective compound against oxidative DNA damage and geraniol (at 125 ppm) also protected cells against methylating DNA damage. This study highlights the potential of EOC such as thymol to protect the colonic epithelium against oxidative DNA damage and geraniol against methylating DNA damage. Further in vivo studies are needed to confirm these findings for safety and efficacy to exploit their potential pharmaceutical or nutraceutical uses for colonic health.


Assuntos
Dano ao DNA/efeitos dos fármacos , Óleos Voláteis/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Ensaio Cometa , Metilação de DNA/efeitos dos fármacos , Eugenol/análise , Eugenol/farmacologia , Humanos , Monoterpenos/análise , Monoterpenos/farmacologia , Óleos Voláteis/análise , Substâncias Protetoras/análise , Terpenos/análise , Terpenos/farmacologia , Timol/análise , Timol/farmacologia
12.
Environ Pollut ; 252(Pt A): 607-615, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31185349

RESUMO

Coke oven emissions (COEs) are common particle pollutants in occupational environment and the major constituents of COEs are polycyclic aromatic hydrocarbons (PAHs). Previously, we identified aberrant methylation of the fms related tyrosine kinase 1 (FLT1) gene over the course of benzo(a)pyrene (BaP)-induced cell transformation via genome-wide methylation array. To quantify FLT1 methylation, we established a bisulfite pyrosequencing assay and examined the FLT1 hypermethylation in several human cancers. The results revealed that 70.0% (21/30 pairs) of lung cancers harbored hypermethylated FLT1 and concomitant suppression of gene expression compared to the adjacent tissues. This implies that FLT1 hypermethylation might play a role in malignant cell transformation. In addition, FLT1 hypermethylation and gene suppression appeared in primary human lymphocytes in a dose-response manner following COEs treatment. To explore whether FLT1 methylation is correlated with COEs exposure and DNA damage, we recruited 144 male subjects who had been exposed to high levels of COEs and 84 male control subjects. Notably, the FLT1 methylation in peripheral blood lymphocytes (PBLCs) of the COEs-exposed group (19.8 ±â€¯3.2%) was enhanced by 17.9% compared to that of the control group (16.8 ±â€¯2.8%) (P < 0.001). The FLT1 methylation status was positively correlated with urinary 1-hydroxypyrene (1-OHP) levels, an internal exposure marker of PAHs (ß = 0.029, 95% CI = 0.010-0.048, P = 0.003) and positively correlated with DNA damage (ßOTM = 0.024, 95% CI = 0.007-0.040, P = 0.005; ßTail DNA = 0.035, 95% CI = 0.0017-0.054, P < 0.001) indicated by comet assay. Taken together, these findings indicate that FLT1 might be a tumor suppressor, and its hypermethylation might contribute to PAHs-induced carcinogenicity.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Adulto , Poluentes Ocupacionais do Ar/análise , Benzo(a)pireno/metabolismo , Biomarcadores/metabolismo , Transformação Celular Neoplásica/metabolismo , Coque , Ensaio Cometa , Dano ao DNA , Metilação de DNA , Humanos , Linfócitos/metabolismo , Masculino , Exposição Ocupacional , Hidrocarbonetos Policíclicos Aromáticos/análise , Pirenos/metabolismo , Sulfitos , Receptor 1 de Fatores de Crescimento do Endotélio Vascular
13.
Arch Insect Biochem Physiol ; 101(4): e21588, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31180585

RESUMO

Boric acid (BA) is widely used in various industrial process and can be accessed to nontarget organisms. This study aimed to investigate the insecticidal effects of BA and its toxic activities with respect to immunologic and genotoxic effects using Galleria mellonella larvae as a model. BA concentrations (78.125-10,000 ppm) were administrated to the larvae using the feeding method. Concentration-dependent mortality was observed in all larval groups. Probit analysis revealed LC30 , LC50 , and LC70 values to be 112.4, 320.1, and 911.4 ppm, respectively. These concentrations were used in all bioassays. Drastic reductions in total hemocyte counts along with changes in differential hemocyte counts were observed following BA treatment. Cell viability assays showed dose-dependent reductions in viable cells and an increase in the necrotic and apoptotic ratios after BA treatment. However, mitotic indices of larval hemocytes did not change at all BA concentrations. The cytotoxic effect of BA led to a significant reduction in cellular immune responses such as encapsulation, melanization, and nodulation activities of treated larvae. While BA increased micronucleus ratios at the highest concentration, comet parameters indicating DNA damage increased in G. mellonella larval hemocytes at all concentrations. These report that BA suppresses the immune system of G. mellonella and also poses risks of genotoxicity at high concentrations.


Assuntos
Ácidos Bóricos/toxicidade , Mariposas/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ensaio Cometa , Relação Dose-Resposta a Droga , Hemócitos/efeitos dos fármacos , Hemolinfa , Inseticidas/toxicidade , Larva/efeitos dos fármacos , Larva/genética , Larva/imunologia , Testes para Micronúcleos , Mariposas/genética , Mariposas/imunologia
14.
Environ Sci Pollut Res Int ; 26(20): 20485-20498, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31102211

RESUMO

Pesticides might increase the production of reactive oxygen species (ROS). Dicamba (DIC) and 2,4-dichlorophenoxyacetic acid (2,4-D) are auxinic herbicides commonly applied in agroecosystems to control unwanted weeds. We analysed the oxidative damage exerted on the fish Cnesterodon decemmaculatus by an acute exposure to DIC- and 2,4-D-based herbicides formulations Banvel® and DMA®, respectively. The Endo III- and Fpg-modified alkaline comet assay was employed for detecting DNA damage caused by oxidative stress, whereas enzymatic and non-enzymatic biomarkers such as the activities of catalase (CAT), glutathione-S-transferase (GST), acetylcholinesterase (AChE), and glutathione content (GSH) were used to assess antioxidant response to these two herbicides. At the DNA level, results demonstrate that both auxinic herbicides induce oxidative damage at purines level. An increase on CAT and GST activities were detected in 48 h- and 96 h-treated specimens with both auxinics. GSH content decreased in fish exposed to DIC during 48 h and to 2,4-D after 96 h of exposure. Additionally, a diminished AChE activity in specimens treated with DIC and 2,4-D was observed only after 96 h. Total protein content decreased in fish exposed to both auxinics during 96 h. These results represent the first evaluation of oxidative damage related to DIC and 2,4-D exposure on a fish species as the Neotropical freshwater teleost C. decemmaculatus.


Assuntos
Ciprinodontiformes/metabolismo , Dicamba/toxicidade , Herbicidas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Ácido 2,4-Diclorofenoxiacético/toxicidade , Animais , Antioxidantes/análise , Antioxidantes/metabolismo , Catalase/metabolismo , Ensaio Cometa , Ciprinodontiformes/fisiologia , Dano ao DNA/efeitos dos fármacos , Dicamba/análogos & derivados , Ecotoxicologia , Biomarcadores Ambientais , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Poluentes Químicos da Água/toxicidade
15.
Sci Total Environ ; 676: 429-435, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31051359

RESUMO

Being exposed to untreated urban and industrial water, the rivers Drenica and Sitnica are considered to be the most polluted ones in the Kosovo. Our previous investigations on the cyto- and genotoxic potential of water samples from these rivers evaluated with primary rat hepatocyte cultures indicated a risk for the health of aquatic organisms. In order to assess the genotoxic risk to aquatic organisms, we therefore performed a two year study (2016-2017) on roach (Rutilus rutilus) from these rivers. Specimens were collected at three locations along the Drenica river and two locations along the Sitnica river, and the genotoxicity was evaluated by the micronucleus as well as the Comet assay (DNA damage) in erythrocytes. The frequencies of micronucleated cells were determined for samples collected in four seasons, whereas the Comet assay was employed on samples collected in five seasons during the two-year period. The data obtained revealed an increase of the frequency of micronucleated erythrocytes from Rutilus rutilus collected at most sampling locations and from both rivers at all seasons investigated. Significant differences to the control (lake Badovc) were found in summer 2016 and spring 2017 samples. When comparing the seasons, the summer 2016 samples were most genotoxic, followed by spring 2017 and autumn 2016. With regard to the Comet assay data, a similar but more prominent "response" was observed. Another important observation is that micronucleus rates as well as DNA damage levels were significantly higher in samples collected in 2016 compared to the respective seasons in 2017. Altogether, the "response" obtained with both markers confirmed a genotoxic risk for fish due the pollution of these rivers. Since there were, however, seasonal and annual variations of the genotoxicity levels further in depth studies have to be carried out addressing the nature of these changes.


Assuntos
Cyprinidae/fisiologia , Monitoramento Ambiental , Poluentes Químicos da Água/toxicidade , Animais , Ensaio Cometa , Kosovo , Testes para Micronúcleos , Medição de Risco , Rios/química , Estações do Ano , Poluentes Químicos da Água/análise
16.
Environ Sci Pollut Res Int ; 26(19): 19445-19452, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31077041

RESUMO

Genotoxicity of three toxic elements (chromium, cadmium, nickel) and a metalloid (arsenic) has been studied in a freshwater fish, Channa punctatus using micronuclei (MN) test, comet assay, and erythrocyte nuclear alterations (ENAs) as fingerprints of genotoxicity. These tests yielded different results suggesting involvement of different mechanisms for their genotoxicity. While highest frequency of blebbed nuclei was observed in chromium-treated fish (6.5 ± 0.76), lowest was observed in cadmium-treated fish (4.0 ± 1.0). Maximum number of notched nuclei was recorded in arsenic-treated fish (5.5 ± 1.15) whereas highest numbers of lobed nuclei were found in cadmium-treated fish (4.5 ± 0.13). These differences might be attributed to selective bioaccumulation and chemodynamics of each element. Other parameters used to determine genotoxicity viz.: lipid peroxidation and DNA damage also suggested different mechanisms of their genotoxicity. It is suggested that an integrative approach, using a battery of tests for determining genotoxicity, should be made while making environmental health risk assessment and ecotoxicological studies of these toxic elements.


Assuntos
Dano ao DNA , Peixes/genética , Água Doce/química , Metais Pesados/toxicidade , Mutagênicos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Ensaio Cometa , Eritrócitos/efeitos dos fármacos , Eritrócitos/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Metais Pesados/análise , Testes para Micronúcleos , Mutagênicos/análise , Poluentes Químicos da Água/análise
17.
Food Chem Toxicol ; 130: 267-275, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31132391

RESUMO

Biosafety is a multidisciplinary approach that encompasses social, societal, ethical issues and policies for the regulations of genetically modified (GM) organisms. The potential health risks associated with GM sugarcane containing AVP1 gene confers resistance against drought and salinity were evaluated by animal feeding studies and some genotoxicity assays. Acute and sub-chronic toxicity examinations were carried out via oral dose administration of GM sugarcane juice supplemented with the normal diet (modified from certified rodent standard diet) on Wistar rats. AVP1 protein concentration in sugarcane juice was 1mg/1 mL. Biochemical, haematological blood analyses were performed and the results revealed that there were non-significant differences among all the treatment groups; GM sugarcane juice, non-GM sugarcane juice and the control group (normal diet and water). Genotoxicity assessment based on the comet assay and the micronucleus assay data exhibited that AVP1 GM sugarcane was not genotoxic or cytotoxic in rat's peripheral blood. These research findings supported the conclusion that GM AVP1 sugarcane was non-toxic in experimental animals. Therefore, data generated through this research work would be helpful for the commercial release of GM AVP1 sugarcane.


Assuntos
Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Pirofosfatase Inorgânica/genética , Pirofosfatase Inorgânica/metabolismo , Saccharum/genética , Animais , Proteínas de Arabidopsis/toxicidade , Peso Corporal , Ensaio Cometa , Feminino , Regulação da Expressão Gênica de Plantas , Pirofosfatase Inorgânica/toxicidade , Masculino , Valor Nutritivo , Plantas Geneticamente Modificadas , Ratos , Ratos Wistar , Testes de Toxicidade
18.
Toxicol Ind Health ; 35(4): 265-276, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30983557

RESUMO

The present study was designed to evaluate genotoxic markers of mancozeb exposure and withdrawal in colon and liver tissues together with histological changes in the gastrointestinal tract of Sprague Dawley rats. Thirty rats were divided into three equal groups; group I: treatment, 250 mg/kg mancozeb dissolved in corn oil administered twice weekly for 7 weeks; group II: withdrawal, the same treatment as group I after which animals were untreated for 5 weeks; group III: control, administered corn oil on the same schedule as group I for 7 weeks. All administrations were by oral gavage. Serum samples were analyzed for biochemical parameters. The comet assay and histopathological examinations were done on liver and colon specimens. The results demonstrated that mancozeb exposure caused significant increases in triglycerides and total cholesterol accompanied by decreases in glucose levels, with extensive DNA damage in liver and colon together with pathological changes in stomach, colon, and liver. Mancozeb withdrawal for 5 weeks improved the lipid and glucose profiles and decreased the degree of DNA damage and changes in the architecture of the stomach, colon, and liver. We concluded that discontinuing exposure to mancozeb fungicide for 5 weeks could ameliorate the adverse effects induced by 7 weeks of exposure to mancozeb. A longer withdrawal time may further reduce the observed genotoxicity.


Assuntos
Colo/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Fígado/efeitos dos fármacos , Maneb/toxicidade , Zineb/toxicidade , Animais , Glicemia/efeitos dos fármacos , Colo/patologia , Ensaio Cometa , Lipídeos/sangue , Fígado/patologia , Masculino , Testes de Mutagenicidade , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Estômago/efeitos dos fármacos , Estômago/patologia
19.
Bull Exp Biol Med ; 166(6): 731-734, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31020577

RESUMO

Antiviral drug Kagocel in concentrations of 0.0008, 0.004, 0.02, 0.1, 0.5, and 2.5 mg/ml with or without metabolic activation does not induce gene mutations in S. typhimurium strains ТА98, ТА100, ТА1535, and ТА1537 and in a combination of E. coli strains pKM101 and uvrA. A single intragastric administration of Kagocel in a daily therapeutic dose and a 10-fold daily therapeutic dose to male mice or multiple administrations in daily therapeutic dose to male and female mice did not led to a significant increase in the percentage of chromosomal aberrations in the bone marrow cells. DNA comet assay revealed no significant increase in the incidence of DNA breaks in cells of mouse testes after single or multiple administration of Kagocel at daily therapeutic and 10-fold daily therapeutic doses. Our results indicate that Kagocel exhibits no genotoxic activity in the studied dose range.


Assuntos
Antivirais/farmacologia , Gossipol/análogos & derivados , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica , Animais , Medula Óssea/química , Medula Óssea/efeitos dos fármacos , Aberrações Cromossômicas , Ensaio Cometa , Cruzamentos Genéticos , Fragmentação do DNA/efeitos dos fármacos , Esquema de Medicação , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Feminino , Gossipol/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética
20.
Environ Sci Pollut Res Int ; 26(15): 15600-15607, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30941715

RESUMO

Several negative health effects have been associated with environmental pollution. Coal mining activities are related to DNA damage. However, the impact of lifestyle as well as environmental exposure must be considered when evaluating the extent of DNA damage. The aim of this cross-sectional study was to analyze nutritional status, dietary patterns, and the prevalence of non-communicable diseases (CNCDs) among coal miners as well as to investigate the correlation of these variables with DNA damage. We used a questionnaire to assess demographics, health, and dietary habits. The nutritional status was measured in terms of BMI (body mass index) and DNA damage was assessed by the comet assay. The sample population was composed of 158 coal miners from the largest coal mining company in South of Brazil, and majority of them were classified as overweight (51.3%) or obese (28.5%). Hypertension was the most common CNCD (50.6%) and a majority of these workers consumed all groups of foods three or more times a week. There was a significant positive correlation between BMI and DNA damage (r = 0.1646, p = 0.04) and this association was stronger (r = 0.2556, p = 0.04) in coal miners with some CNCD. There was no significant correlation between dietary patterns and DNA damage in coal miners. These results suggest that the nutritional status and CNCD increase the extent of DNA damage in coal miners. Since this population is at high occupational risk, specific strategies should be designed to improve the health of these workers, aiming to achieve health equity.


Assuntos
Minas de Carvão/métodos , Carvão Mineral/toxicidade , Dano ao DNA , Doenças não Transmissíveis/epidemiologia , Exposição Ocupacional/efeitos adversos , Índice de Massa Corporal , Brasil , Ensaio Cometa , Estudos Transversais , Humanos , Hipertensão , Mineradores , Estado Nutricional , Prevalência
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