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1.
Einstein (Sao Paulo) ; 17(4): eAO4742, 2019 Sep 09.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31508660

RESUMO

OBJECTIVE: To evaluate the induction of DNA damage in peripheral blood mononuclear cells of patients with sickle cell disease, SS and SC genotypes, treated with hydroxyurea. METHODS: The study subjects were divided into two groups: one group of 22 patients with sickle cell disease, SS and SC genotypes, treated with hydroxyurea, and a Control Group composed of 24 patients with sickle cell disease who were not treated with hydroxyurea. Peripheral blood samples were submitted to peripheral blood mononuclear cell isolation to assess genotoxicity by the cytokinesis-block micronucleus cytome assay, in which DNA damage biomarkers - micronuclei, nucleoplasmic bridges and nuclear buds - were counted. RESULTS: Patients with sickle cell disease treated with hydroxyurea had a mean age of 25.4 years, whereas patients with sickle cell disease not treated with hydroxyurea had a mean age of 17.6 years. The mean dose of hydroxyurea used by the patients was 12.8mg/kg/day, for a mean period of 44 months. The mean micronucleus frequency per 1,000 cells of 8.591±1.568 was observed in the Hydroxyurea Group and 10.040±1.003 in the Control Group. The mean frequency of nucleoplasmic bridges per 1,000 cells and nuclear buds per 1,000 cells for the hydroxyurea and Control Groups were 0.4545±0.1707 versus 0.5833±0.2078, and 0.8182±0.2430 versus 0.9583±0.1853, respectively. There was no statistically significant difference between groups. CONCLUSION: In the study population, patients with sickle cell disease treated with the standard dose of hydroxyurea treatment did not show evidence of DNA damage induction.


Assuntos
Anemia Falciforme/genética , Dano ao DNA/efeitos dos fármacos , Hidroxiureia/farmacologia , Inibidores da Síntese de Ácido Nucleico/farmacologia , Adolescente , Adulto , Anemia Falciforme/tratamento farmacológico , Criança , Pré-Escolar , Citocinese , Dano ao DNA/genética , Feminino , Humanos , Hidroxiureia/efeitos adversos , Hidroxiureia/uso terapêutico , Masculino , Testes para Micronúcleos , Pessoa de Meia-Idade , Testes de Mutagenicidade , Mutação/efeitos dos fármacos , Inibidores da Síntese de Ácido Nucleico/efeitos adversos , Inibidores da Síntese de Ácido Nucleico/uso terapêutico , Adulto Jovem
2.
Arq Gastroenterol ; 56(2): 155-159, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31460579

RESUMO

BACKGROUND: Gastric cancer is known as the fourth most common cancer. Current treatments for cancer have damaged the sensitive tissues of the healthy body, and in many cases, cancer will be recurrent. Therefore, need for treatments that are more effective is well felt. Researchers have recently shifted their attention towards antipsychotic dopamine antagonists to treat cancer. The anticancer activities of aripiprazole remain unknown. OBJECTIVE: This study aimed to evaluate the efficacy and safety of aripiprazole on gastric cancer and normal cell lines. METHODS: In this regard, the cytotoxicity and genotoxicity of aripiprazole were investigated in MKN45 and NIH3T3 cell lines by methyl tetrazolium assay and on peripheral blood lymphocytes by micronucleus assay. For this purpose, cells were cultured in 96 wells plate. Stock solutions of aripiprazole and cisplatin were prepared. After cell incubation with different concentrations of aripiprazole (1, 10, 25, 50, 100 and 200 µL), methyl tetrazolium solution was added. For micronucleus assay fresh blood was added to RPMI culture medium 1640 supplemented, and different concentrations of aripiprazole (50, 100 and 200 µL) were added. RESULTS: The finding of present study showed that the IC50 of aripiprazole in the cancer cell line (21.36 µg/mL) was lower than that in the normal cell line (54.17 µg/mL). Moreover, the micronucleus assay showed that the frequency of micronuclei of aripiprazole at concentrations below 200 µM was much less than cisplatin. CONCLUSION: Aripiprazole can be a good cytotoxic compound and good candidate for further studies of cancer therapy.


Assuntos
Aripiprazol/toxicidade , Linfócitos/efeitos dos fármacos , Animais , Humanos , Camundongos , Testes para Micronúcleos/métodos , Testes de Mutagenicidade , Células NIH 3T3/efeitos dos fármacos
3.
Chem Biol Interact ; 311: 108776, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31369745

RESUMO

Omeprazole (OM), a prototype proton pump inhibitor, oxidizes thiol groups and induces DNA damage. The aim of this study was to evaluate the oxidative effects of omeprazole and its interactions with ascorbic acid (AA, 50 µM) and retinol palmitate (RP) in proficient and deficient Saccharomyces cerevisiae strains, as well as levels of cytogenetic damage in Sarcoma 180 (S180) cells. Omeprazole was tested at concentrations of 10, 20 and 40 µg/mL, whereas H2O2 (10 mM), cyclophosphamide (20 mg/mL), and saline (0.9% NaCl solution) were employed as stressor, positive control, and negative control, respectively. Results revealed that omeprazole concentration-dependently induces oxidative effects in S. cerevisiae strains. However, omeprazole co-treated with ascorbic acid (50 µM) and retinol palmitate (100 IU) significantly modulated the oxidative damage inflected on the S. cerevisiae strains. Furthermore, omeprazole did not produce micronucleus formation and chromosomal bridges in S180 cells, but induced shoots. Significant increase in karyolysis and karyorrhexis were also observed with the omeprazole treated groups, which was modulated by co-treatment with ascorbic acid and retinol palmitate. Taken all together, it is suggested that ascorbic acid and retinol palmitate can substantially modulate the oxidative damage caused by omeprazole on the S. cerevisiae strains, however, much precaution is recommended with omeprazole and antioxidant co-treatment.


Assuntos
Ácido Ascórbico/farmacologia , Aberrações Cromossômicas/efeitos dos fármacos , Omeprazol/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos dos fármacos , Vitamina A/análogos & derivados , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclofosfamida/toxicidade , Peróxido de Hidrogênio/toxicidade , Camundongos , Testes para Micronúcleos , Vitamina A/farmacologia
4.
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
5.
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
6.
Rev Assoc Med Bras (1992) ; 65(6): 870-879, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31340319

RESUMO

This study aimed to assess the prevalence of medical and nonmedical use of psychiatric medication among undergraduate students of health sciences from a public university in Brasil. Another objective was to determine the frequency of nuclear morphological abnormalities in the buccal mucosa of students using psychiatric drugs. A cross-sectional study based on a Web survey was carried out with 375 health sciences undergraduate students from schools of Pharmacy, Physical Education, Nutrition, and Medicine. Additionally, spontaneous genetic damages in exfoliated cells of the buccal mucosa of 41 individuals by counting micronucleus (MN) and binucleated (BN) cells frequencies were evaluated. The results showed 76 (20.3%) of students reported the use of psychotropic drugs after enrolling in university. The majority of these students were from Pharmacy and Medicine programs, females, aged between 18-25 years old, nonsmokers, alcohol addicts, and with a family history of mental illness. In addition, Medical students, individuals with high-income, who live alone and are in the last period of the program are more likely to use psychotropic drugs. Moreover, exposure to psychiatric medication was able to increase the number of binucleated cells. These results provide evidence that the use of psychoactive drugs is increased in the academic context and may be related to the failure of the cell cycle.


Assuntos
Uso Indevido de Medicamentos/estatística & dados numéricos , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/patologia , Psicotrópicos/uso terapêutico , Estudantes de Ciências da Saúde/estatística & dados numéricos , Adolescente , Adulto , Brasil , Estudos Transversais , Feminino , Humanos , Masculino , Testes para Micronúcleos , Fatores de Risco , Fatores Socioeconômicos , Inquéritos e Questionários , Universidades , Adulto Jovem
7.
Chemosphere ; 232: 337-344, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31154195

RESUMO

In this study, we investigated the effects of three binary mixtures of pesticide formulations commonly used in soybean crop: Cypermethrin Atanor® (25% -CYP), Chlorpyrifos Lorsban 48E® (48% -CPF) and Glyphosate Roundup® Full II (66.2% -GLY) on broad-snouted caiman (Caiman latirostris) hatchlings exposed by voluntary immersion under controlled condition. Genotoxicity was evaluated in peripheral blood erythrocytes through the micronucleus (MN) test and other nuclear abnormalities (NAs) and besides, growth of caiman was analyzed in each experimental group. The results showed that pesticide formulations tested, at concentrations similar to those recommended for application in the field, induced an increase in the frequency of micronucleus (FMN; p = 0.001) and Notched nuclei (NN; p = 0.010) in the mixture CYP + CPF, while an increase in the frequency of buds and NN was observed in the mixture of GLY + CYP (pbuds = 0.016 and pNN = 0.021), compared to the vehicle control (VC). On the contrary, a possible antagonistic action was observed between the components in the mixture GLY + CPF. Growth was not affected in any exposed groups (p > 0.05). There was a clutch effect in the frequency of binucleated erythrocytes (BiN; p = 0.011), total length (TL; p = 0.001) and snout-vent length (SVL; p = 0.031). Biomarkers used in this study are considered important predictive tools for the evaluation of xenobiotics. In this study, we demonstrated genotoxicity of pesticide mixtures under conditions that simulate the real situation of exposure suffered by caiman and other wild species in Argentina.


Assuntos
Jacarés e Crocodilos/fisiologia , Testes para Micronúcleos , Mutagênicos/toxicidade , Praguicidas/toxicidade , Animais , Argentina , Clorpirifos/toxicidade , Dano ao DNA , Eritrócitos/efeitos dos fármacos , Glicina/análogos & derivados , Piretrinas/toxicidade
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 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
11.
Klin Lab Diagn ; 64(4): 229-233, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31108036

RESUMO

The Russian northern regions development is associated with the extraction and processing of natural resources, which leads to environmental pollution and makes the task of sanitary-hygienic monitoring relevant. Buccal micronucleus cytome assay is one of the toxicological methods for human population studies. Studies on the inter-latitudinal comparison of Buccal micronucleus cytome assay are lacking, therefore there are difficulties in comparing the results obtained in the Russian Arctic with data from more southern regions. The aim of this study is to compare cytogenetic abnormalities in the buccal epithelium in two groups of older schoolchildren living in high and middle latitudes. The study was conducted in the city of Apatity (Murmansk region, 67 ° 34'03 ″ N, 33 ° 23'36 ″ E) and the city of Serpukhov (Moscow region, 54 ° 54 '56 ″ N, 37 ° 24 '40 "E). A total of 61 children were examined: 41 children from the Apatity and 20 children from the Serpukhov (16-18 years old). The Buccal micronucleus cytome assay was carried out according to an international protocol. It was shown that the average frequency values of the cells with micronucleus in the comparison groups of schoolchildren living in high and middle latitudes did not significantly differ and did not exceed the values for the average population norm. The frequency of cells with nuclear buds and two nucleus was significantly higher in the group of schoolchildren living in middle latitudes, which, in turn, is compensated by a higher rate of elimination of cells with impaired. Therefore, when comparing Buccal micronucleus cytome assay data, it is quite possible not to take into account the breadth of the studied groups.


Assuntos
Células Epiteliais/citologia , Mucosa Bucal/citologia , Adolescente , Regiões Árticas , Humanos , Testes para Micronúcleos , Moscou , Federação Russa
12.
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
13.
Environ Sci Pollut Res Int ; 26(19): 19676-19683, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31079294

RESUMO

Since many different pesticides have been used occupationally, there have been inconsistent results regarding DNA damages among greenhouse workers. Thus, the aim of the study is to evaluate DNA damages, cell death, and chromosomal instability by using the buccal micronucleus cytome (BMcyt) assay in greenhouse workers and to compare those with a non-exposed group. The BMcyt assay was applied to the exfoliated buccal cell samples collected from 66 pesticide-exposed and 50 non-exposed individuals. We evaluated the frequency of micronucleus (MN), nuclear bud (NBUD), binucleated (BN) cells, and karyolitic (KL), pyknotic (PY), and karyorrhectic (KH) cells. The results showed that the MN, BN, PY, and KH frequencies of the pesticide-exposed group were significantly higher than those of the controls (P Ë‚ 0.05, P Ë‚ 0.05, P Ë‚ 0.01, and P Ë‚ 0.05, respectively). We observed that the MN, BN, PY, and KH frequencies in the autumn were statistically different compared with those in the control group (P = 0.037 for MN, P = 0.001 for BN, P = 0.016 for PY, and P = 0.033 for KH). The same comparison was done in the spring for the control, and there was a statistically significant difference for MN (P = 0.046) and PY (P = 0.014). We can conclude that pesticide exposure in greenhouse workers was one of the factors that altered DNA damages, cell death, and chromosomal instability in oral mucosa cells.


Assuntos
Instabilidade Cromossômica/efeitos dos fármacos , Dano ao DNA , Monitoramento Ambiental/métodos , Fazendeiros , Mucosa Bucal/efeitos dos fármacos , Exposição Ocupacional/análise , Praguicidas/toxicidade , Adulto , Morte Celular/efeitos dos fármacos , Feminino , Humanos , Masculino , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Testes para Micronúcleos , Mucosa Bucal/citologia , Exposição Ocupacional/efeitos adversos , Turquia
14.
Environ Pollut ; 250: 831-838, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31051394

RESUMO

Nano- and microplastics have been widely spread in environmental matrices, especially in marine and terrestrial systems. In this study, higher plant Vicia faba root tips were exposed to 5 µm and 100 nm with 10, 50 and 100 mg/L polystyrene fluorescent microplastics (PS-MPs) for 48 h. Root length, weight, oxidative stress and genotoxicity of V. faba were assessed to investigate toxic effects of PS-MPs. The results showed that the biomass and catalase (CAT) enzymes activity of V. faba roots decreased under 5 µm PS-MPs whereas superoxide dismutase (SOD) and peroxidase (POD) enzymes activity significantly increased. Under the 100 nm PS-MPs exposure a significant decrease of growth was observed only at the highest concentration (100 mg/L). However, micronucleus (MN) test and antioxidative enzymes activities showed that 100 nm PS-MPs induce higher genotoxic and oxidative damage to V. faba than 5 µm PS-MPs. Furthermore, the laser confocal scanning microscopy (LCSM) demonstrated that 100 nm PS-MPs can accumulate in V. faba root and most probably block cell connections or cell wall pores for transport of nutrients. These findings provide a new insight into the toxic effects of microplastics on V. faba, and further apply to the ecological risk assessment of microplastics on higher plants.


Assuntos
Antioxidantes/metabolismo , Dano ao DNA , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Poliestirenos/toxicidade , Vicia faba/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ecotoxicologia , Testes para Micronúcleos , Modelos Teóricos , Tamanho da Partícula , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/enzimologia , Raízes de Plantas/genética , Vicia faba/enzimologia , Vicia faba/genética
15.
Food Chem Toxicol ; 130: 79-88, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31103741

RESUMO

Pyrrolizidine alkaloids (PA) are widely distributed phytotoxins contaminating food and feed. Hepatic enzymes are considered to bioactivate PA. Previous studies showed differences in the metabolism rate in liver homogenates of different species. Thus, uncertainty remains with respect to the relevance of human metabolism. Our study aimed to analyze whether the PA representative lasiocarpine is toxified by human cytochrome P450 (CYP) enzymes. We compared the metabolic elimination of lasiocarpine in the presence of rat and human S9 fractions and liver microsomes. Experiments with the potent CYP3A/Cyp3a inhibitor ketoconazole and supersomes containing individual human and rat CYPs revealed that enzymes of the CYP3A/Cyp3a family of both species are of major relevance for lasiocarpine metabolism. To assess if metabolism by human CYP3A4 results in a toxification of lasiocarpine we performed experiments with V79 cells. γH2AX and micronucleus formation were analyzed as endpoints for genotoxicity. No effects were observed in the wildtype cells, which lack CYP activity. By contrast, a V79 clone engineered for expression of human CYP3A4 showed concentration-dependent γH2AX and micronucleus formation. Concluding, our results showed the CYP3A4-dependent formation of genotoxic metabolites of lasiocarpine. The results confirm previous data indicating the need to include metabolism of PA for human risk assessment.


Assuntos
Citocromo P-450 CYP3A/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Alcaloides de Pirrolizidina/metabolismo , Alcaloides de Pirrolizidina/toxicidade , Animais , Linhagem Celular , Citocromo P-450 CYP3A/genética , Histonas , Humanos , Testes para Micronúcleos , Microssomos Hepáticos/metabolismo , Estrutura Molecular , Ratos
16.
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
17.
Regul Toxicol Pharmacol ; 105: 36-41, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30935955

RESUMO

Food-borne alkenylbenzenes are potential risks for human health because they are known to induce liver tumors in rodent bioassays at high dose levels. This carcinogenicity is ascribed to the conversion of their 1'-hydroxymetabolites to the ultimate DNA reactive and carcinogenic 1'-sulfoxymetabolites. The aim of this study was to investigate the in vitro genotoxicity of some botanical extracts used as Plant Food Supplements (PFS) and to compare it with the individual substances, estragole, safrole and their 1'-hydroxy-derivative activity. The genotoxicity of the PFSs was evaluated in HepG2 cell line by comet and micronucleus assays. Unlike the 1'-hydroxy derivatives, PFS extracts and parent alkenylbenzenes did not show genotoxicity at any of the tested concentrations. The sulfotransferase inhibitor pentachlorophenol (PCP) reduced the 1'-hydroxy compound-induced response in the comet and micronucleus assays, thus confirming that the formation of sulfoxy-metabolites is essential for inducing genotoxic effects. When the cells were treated with hydroxylated alkenylbenzenes in the presence of PFSs, a reduction in genotoxic activity of synthetic compounds was observed.


Assuntos
Anisóis/toxicidade , Derivados de Benzeno/toxicidade , Extratos Vegetais/toxicidade , Safrol/toxicidade , Derivados de Benzeno/química , Ensaio Cometa , Células Hep G2 , Humanos , Testes para Micronúcleos , Mutagênicos/toxicidade , Extratos Vegetais/química
18.
Arch Environ Contam Toxicol ; 77(1): 22-28, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30949743

RESUMO

Many agricultural practices cause environmental degradation that affects the cellular integrity of anurans. In the present study, we provided in situ data of Dendropsophus minutus, Physalaemus cuvieri, and Scinax fuscovarius collected in soybean/corn and conservation units in the Brazilian Cerrado. The in situ data showed no significant variation in the micronucleus frequency between the sites, only the reniform cells had a higher rate for the agricultural environment. A combined analysis of all nuclear erythrocyte abnormalities (ENAs = nuclear buds, reniform nuclei, apoptotic cell, binucleated, and anucleated cells) was recorded higher frequencies in farmland. Overall, Scinax fuscovarius was considered the best potential bioindicator for soybean/corn plantations. Finally, we recommend expanding the micronucleus test for in situ studies to expand our understanding of the sensitivity of native anuran species and provide a more systematic assessment of the adverse effects of environmental pollutants on wildlife.


Assuntos
Agricultura , Anuros/genética , Poluentes Ambientais/toxicidade , Larva/efeitos dos fármacos , Animais , Monitoramento Ambiental , Larva/genética , Testes para Micronúcleos
19.
Asian Pac J Cancer Prev ; 20(4): 1045-1050, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31030472

RESUMO

Objectives: Vast number of studies show the relationship between aneuploidy and cancer. Ionizing radiation in addition to induce all kinds of damages to the cells and structure of chromosomes, is also able to induce aneuploidy through direct damages to chromosome division apparatus. Also irradiation of the cells induces mutations in several genes which might be involved in cell division fidelity and play a role in reversing the effect of aneugens. Therefore, irradiation of cells and tissues might produce sensitivity to agents with aneugenic capability in irradiated cells. Methods: To investigate the persistent genomic effect of ionizing irradiation on chromosomal instability, L929 cells were gamma irradiated with the dose of 2 Gy. Cells were left to recover from the harmful effect of irradiation. They were treated with low dose of vinblastine (0.5 ng.ml-1) 72h post-gamma irradiation. Finally, the induced chromosomal abnormalities were scored using micronucleus assay in cytokinesis-blocked binucleated cells (MnBi). Results: Irradiation-recovered L929 cells treated with vinblastine showed a statistically higher frequency of MnBi compared to non-irradiated and vinblastine treated cells. Conclusion: The results indicate that gamma irradiation, in addition to direct induction of chromosomal damages, is also able to create persisting genomic sensitivity in the cells to chromosomal instability, which is detectable when exposed to the second stimulus.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Núcleo Celular/genética , Aberrações Cromossômicas , Citocinese , Fibroblastos/patologia , Raios gama , Vimblastina/farmacologia , Divisão Celular , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Fibroblastos/efeitos da radiação , Humanos , Testes para Micronúcleos
20.
Int J Mol Sci ; 20(8)2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30999684

RESUMO

Goeckerman therapy (GT) of psoriasis vulgaris is based on the application of crude coal tar and ultraviolet radiation. We investigated DNA damage by the number of micronucleated binucleated cells (MNBC) in lymphocytes, serum homocysteine, vitamin B12, folic acid, and two polymorphisms (C677T and A1298C) in the MTHFR gene in 35 patients with exacerbated psoriasis vulgaris classified according to the psoriasis area and severity index (PASI) score and treated by GT. The median of PASI score decreased from nineteen to five, and MNBC increased from 10 to 18‰ after GT (p < 0.001 in both cases). Correlations of MNBC with homocysteine (Spearman's rho = 0.420, p = 0.012) and vitamin B12 (rho = -0.389, p = 0.021) before the therapy were observed. Hyperhomocysteinemia was an independent predictor of genotoxicity (OR 9.91; 95% CI, 2.09-55.67; p = 0.003). Homocysteine was higher in females than in males (13 vs. 12 µmol/L, p = 0.045). In contrast, vitamin B12 levels in the females were lower than in the males (160 vs. 192 pmol/L, p = 0.047). Vitamin B12 in the females were negatively influenced by smoking status (160 pmol/L in smokers vs. 192 pmol/L in non-smokers, p = 0.025). A significantly higher MNBC was found in CC homozygous patients (A1298C polymorphism) than in AC heterozygotes (32 vs. 16‰, p = 0.005) and AA homozygotes (32 vs. 18‰, p = 0.036). Our data showed that homocysteine participates in the pathogenesis of psoriasis. Its serum levels correlated with MNBC and allowed the prediction of DNA damage to appear within GT. Both micronutrients status and homocysteine metabolic pathway contribute to the genotoxicity of GT.


Assuntos
Alcatrão/uso terapêutico , Ceratolíticos/uso terapêutico , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Psoríase/genética , Psoríase/terapia , Terapia Ultravioleta/métodos , Adulto , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Ácido Fólico/sangue , Homocisteína/sangue , Humanos , Testes para Micronúcleos , Micronutrientes/sangue , Pessoa de Meia-Idade , Psoríase/sangue , Psoríase/patologia , Vitamina B 12/sangue
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