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1.
J Water Health ; 17(5): 762-776, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31638027

RESUMO

Disinfection is intended to improve drinking water quality and human health. Although disinfectants may transform organic matter and form disinfection by-products (DBPs), many are branded as cyto- and genotoxic. Traditionally, research focuses on the effects of DBPs on human health, but cytogenic impacts on aquatic organisms still remain ill defined. The current study examines the potential toxic effect of chloroform and iodoform (DBPs) on Cyprinus carpio, selected as a model organism. Fish specimens were exposed to various concentrations of DBPs primarily based on LD50 values, where acute toxicity was monitored for 96 h. Headspace SPME extraction through gas chromatography was employed to assess the effects of spiked DBPs doses in fish blood. Cytotoxicity was monitored using Comet assay. Tail length, tail DNA, and olive tail moment values were quantified to be significant (P < 0.05) as compared to control. A statistically significant (P < 0.05) decrease in all blood parameters (hematology) was observed. Changes in biochemical indices (glucose, total protein, and alanine aminotransferase (ALT)) were also significant. ALT secretion was significantly increased (93 ± 0.05 and 82.8 ± 0.1 U/L) at higher concentration compared to control (56 ± 0.1 U/L), suggesting liver damage. Results demonstrated that iodoform was statistically more damaging as compared to chloroform.


Assuntos
Carpas/fisiologia , Desinfetantes/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Dano ao DNA , Desinfecção , Hematologia , Humanos
2.
An Acad Bras Cienc ; 91(3): e20180994, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31596391

RESUMO

Herbal medicines are efficient to reduce side effects in the fight against glioblastoma, which plays a critical role within brain cancer species. The recent studies designated for testing the effects of lichens that have shown numerous anticancer activities on glioblastoma so far. In the present study, different concentrations of water extract obtained from Usnea longissima Ach. were used in order to determine cytotoxic (via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase tests), antioxidant (via total antioxidant capacity test), pro-oxidant (via total oxidant status test) and genotoxic (via 8-hydroxy-2'-deoxyguanosine test) effects of them on human U87MG-glioblastoma cancer cell lines. Primary mixed glial-neuronal non-cancerous cells from Sprague-Dawley rats were also utilized to measure the effects of treatments on non-cancerous cells. Based on median inhibitory concentration values, the data belonged to non-cancerous cells (2486.71 mg/L) showed distinct towering compared to U87MG (80.93 mg/L) cells. The viability of non-cancerous and U87MG cells exposed to extract is decreased in a dose dependent manner. It was also showed that low concentrations of extract notably increased total antioxidant capacity on non-cancerous cells. In addition, various phenolic compounds in extract were detected through high-performance liquid chromatography. The recent results encourage that extract will be able to have therapeutic potential against glioblastoma.


Assuntos
Antioxidantes/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Extratos Vegetais/farmacologia , Usnea/química , Animais , Antioxidantes/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Humanos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-Dawley
3.
Medicine (Baltimore) ; 98(39): e17373, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574886

RESUMO

Ionizing radiation can induce deoxyribonucleic acid (DNA) methylation pattern change, and ionizing radiation-induced oxidative damage may also affect DNA methylation status. However, the influence of low-dose ionizing radiation, such as occupational radiation exposure, on DNA methylation is still controversial.By investigating the relationship between occupational radiation exposure and DNA methylation changes, we evaluated whether radiation-induced oxidative damage was related to DNA methylation alterations and then determined the relationship among occupational radiation level, DNA methylation status, and oxidative damage in interventional physicians.The study population included 117 interventional physicians and 117 controls. We measured global methylation levels of peripheral blood leukocyte DNA and expression level of DNA methyltransferase (Dnmts) and homocysteine (Hcy) in serum to assess the DNA methylation status of the body. We measured 8-hydroxy-2'-deoxyguanosine (8-OHDG) and 4-hydroxynonenal (4-HNE) levels as indices of oxidative damage. Relevance analysis between multiple indices can reflect the relationship among occupational radiation exposure, DNA methylation changes, and oxidative damage in interventional physicians.The expression levels of Dnmts, 4-HNE, and 8-OHDG in interventional physicians were higher than those in controls, while there was no statistical difference in total DNA methylation rate and expression of Hcy between interventional physicians and controls. Total cumulative personal dose equivalent in interventional physicians was positively correlated with the expression levels of Dnmts, 8-OHDG, and 4-HNE. The expression levels of 8-OHDG in interventional physicians were negatively correlated with global DNA methylation levels and positively correlated with the expression levels of Hcy.Occupational radiation exposure of interventional physicians has a certain effect on the expression of related enzymes in the process of DNA methylation, while ionizing radiation-induced oxidative damage also has a certain effect on DNA methylation. However, there was no evidence that dose burden of occupational exposure was associated to changes of DNA methylation status of interventional physicians, since it is rather unclear which differences are observed among the effects produced by radiation exposure and oxidative damage.


Assuntos
Dano ao DNA/efeitos da radiação , Metilação de DNA/efeitos da radiação , Exposição Ocupacional/análise , Estresse Oxidativo/efeitos da radiação , Exposição à Radiação/análise , Radiologia Intervencionista/estatística & dados numéricos , Adulto , Aldeídos/sangue , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangue , Feminino , Homocisteína/sangue , Humanos , Leucócitos/metabolismo , Masculino , Metiltransferases/sangue , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Médicos/estatística & dados numéricos , Exposição à Radiação/efeitos adversos
4.
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
5.
Enzymes ; 45: 1-26, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31627875

RESUMO

DNA polymerase ß plays a central role in the base excision DNA repair pathway that cleanses the genome of apurinic/apyrimidinic (AP) sites. AP sites arise in DNA from spontaneous base loss and DNA damage-specific glycosylases that hydrolyze the N-glycosidic bond between the deoxyribose and damaged base. AP sites are deleterious lesions because they can be mutagenic and/or cytotoxic. DNA polymerase ß contributes two enzymatic activities, DNA synthesis and lyase, during the repair of AP sites; these activities reside on carboxyl- and amino-terminal domains, respectively. Accordingly, its cellular, structural, and kinetic attributes have been extensively characterized and it serves as model enzyme for the nucleotidyl transferase reaction utilized by other replicative, repair, and trans-lesion DNA polymerases.


Assuntos
DNA Polimerase beta/metabolismo , Reparo do DNA , Replicação do DNA , Animais , Dano ao DNA , DNA Glicosilases/metabolismo
6.
Enzymes ; 45: 139-181, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31627876

RESUMO

DNA contains information that must be safeguarded, but also accessed for transcription and replication. To perform replication, eukaryotic cells use the B-family DNA polymerase enzymes Polδ and Polɛ, which are optimized for accuracy, speed, and processivity. The molecular basis of these high-performance characteristics causes these replicative polymerases to fail at sites of DNA damage (lesions), which would lead to genomic instability and cell death. To avoid this, cells possess additional DNA polymerases such as the Y-family of polymerases and the B-family member Polζ that can replicate over sites of DNA damage in a process called translesion synthesis (TLS). While able to replicate over DNA lesions, the TLS polymerases exhibit low-fidelity on undamaged DNA and, consequently, must be prevented from replicating DNA under normal circumstances and recruited only when necessary. The replicative bypass of most types of DNA lesions requires the consecutive action of these specialized TLS polymerases assembled into a dynamic multiprotein complex called the Rev1/Polζ mutasome. To this end, posttranslational modifications and a network of protein-protein interactions mediated by accessory domains/subunits of the TLS polymerases control the assembly and rearrangements of the Rev1/Polζ mutasome and recruitment of TLS proteins to sites of DNA damage. This chapter focuses on the structures and interactions that control these processes underlying the function of the Rev1/Polζ mutasome, as well as the development of small molecule inhibitors of the Rev1/Polζ-dependent TLS holding promise as a potential anticancer therapy.


Assuntos
Dano ao DNA , Reparo do DNA , Replicação do DNA , DNA/biossíntese , DNA Polimerase Dirigida por DNA/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética
7.
Enzymes ; 45: 257-287, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31627879

RESUMO

The mitochondrial genome encodes proteins essential for the oxidative phosphorylation and, consequently, for proper mitochondrial function. Its localization and, possibly, structural organization contribute to higher DNA damage accumulation, when compared to the nuclear genome. In addition, the mitochondrial genome mutates at rates several times higher than the nuclear, although the causal relationship between these events are not clearly established. Maintaining mitochondrial DNA stability is critical for cellular function and organismal fitness, and several pathways contribute to that, including damage tolerance and bypass, degradation of damaged genomes and DNA repair. Despite initial evidence suggesting that mitochondria lack DNA repair activities, most DNA repair pathways have been at least partially characterized in mitochondria from several model organisms, including humans. In this chapter, we review what is currently known about how the main DNA repair pathways operate in mitochondria and contribute to mitochondrial DNA stability, with focus on the enzymology of mitochondrial DNA repair.


Assuntos
Dano ao DNA , Reparo do DNA , DNA Mitocondrial/metabolismo , Mitocôndrias/genética , Humanos
8.
Enzymes ; 45: 27-57, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31627880

RESUMO

Repair of damaged DNA plays a crucial role in maintaining genomic integrity and normal cell function. The base excision repair (BER) pathway is primarily responsible for removing modified nucleobases that would otherwise cause deleterious and mutagenic consequences and lead to disease. The BER process is initiated by a DNA glycosylase, which recognizes and excises the target nucleobase lesion, and is completed via downstream enzymes acting in a well-coordinated manner. A majority of our current understanding about how BER enzymes function comes from in vitro studies using free duplex DNA as a simplified model. In eukaryotes, however, BER is challenged by the packaging of genomic DNA into chromatin. The fundamental structural repeating unit of chromatin is the nucleosome, which presents a more complex substrate context than free duplex DNA for repair. In this chapter, we discuss how BER enzymes, particularly glycosylases, engage in the context of packaged DNA with insights obtained from both in vivo and in vitro studies. Furthermore, we review factors and mechanisms that can modify chromatin architecture and/or influence DNA accessibility to BER machinery, such as the geometric location of the damage site, nucleosomal DNA unwrapping, histone post-translational modifications, histone variant incorporation, and chromatin remodeling.


Assuntos
Cromatina/química , Cromatina/genética , Dano ao DNA , Reparo do DNA , DNA/química , DNA/metabolismo , Montagem e Desmontagem da Cromatina , DNA/genética , Histonas/química , Histonas/metabolismo , Nucleossomos/química , Nucleossomos/genética
9.
Enzymes ; 45: 59-97, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31627883

RESUMO

The nucleotide excision repair (NER) system removes a variety of types of helix-distorting lesions from DNA through a dual incision mechanism, in which the damaged nucleotide bases are excised in the form of a small, excised, damage-containing single-stranded DNA oligonucleotide (sedDNA). Damage removal leaves a gap in the DNA template that must then be filled in by the action of a DNA polymerase and ligated to the downstream phosphodiester backbone in the DNA to complete the repair reaction. Defects in damage removal, sedDNA processing, or gap filling have the potential to be mutagenic and lethal to cells, and thus several human pathologies, including cancer and aging, are associated with defects in NER. This review summarizes our current understanding of NER with a focus on the enzymes that excise sedDNAs and restore the duplex DNA to its native state in human cells.


Assuntos
Dano ao DNA , Reparo do DNA , Replicação do DNA , DNA/química , DNA/metabolismo , DNA/biossíntese , DNA/genética , DNA de Cadeia Simples/química , DNA de Cadeia Simples/genética , DNA de Cadeia Simples/metabolismo , Humanos
10.
Enzymes ; 45: 99-138, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31627884

RESUMO

Nucleotide excision repair (NER) is a versatile DNA repair pathway that eliminates various helix-distorting base lesions such as ultraviolet (UV)-induced photolesions. Several recessive human disorders, such as xeroderma pigmentosum (XP), are caused by hereditary defects in NER, implying that the pathway plays critical roles in suppressing diverse pathogenic processes, including carcinogenesis. In general, discrimination of lesion sites from intact DNA, which is present in vast excess, is a key determinant of the overall efficiency of DNA repair. In mammalian cells, global genomic NER lesion recognition is initiated by the XPC protein complex, which achieves broad DNA-binding specificity by sensing destabilized base pairs rather than lesions per se. To avert unnecessary incisions at lesion-free sites, and thereby ensure the fidelity of the repair system, transcription factor IIH and the XPA protein then verify the presence of relevant lesions at suspicious sites bound by XPC. In the case of UV-induced photolesions, a specialized lesion sensor called UV-damaged DNA-binding protein (UV-DDB) contributes to efficient lesion recognition and the recruitment of XPC to lesion sites. The ubiquitin-proteasome system plays a crucial role in the handoff of lesions from UV-DDB to XPC and the subsequent NER process. In addition, recognition of lesions targeted by global genomic NER is intricately regulated by higher-order chromatin structures, which play distinct roles depending on the type of lesion.


Assuntos
Dano ao DNA , Reparo do DNA , Animais , Proteínas de Ligação a DNA/metabolismo , Humanos , Complexo de Endopeptidases do Proteassoma/metabolismo , Fator de Transcrição TFIIH/metabolismo , Ubiquitina/metabolismo , Raios Ultravioleta/efeitos adversos , Proteína de Xeroderma Pigmentoso Grupo A/metabolismo
11.
J Environ Sci (China) ; 85: 94-106, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31471036

RESUMO

Titanium dioxide nanoparticles (TiO2 NPs) are subjected to various transformation processes (chemical, physical and biological processes) in the environment, potentially affecting their bioavailability and toxic properties. However, the size variation of TiO2 NPs during aging process and subsequent effects in mammalian cells are largely unknown. The aim of this study was to illustrate the adverse effects of TiO2 NPs in different sizes (5, 15 and <100 nm) during aging process on human-hamster hybrid (AL) cells. There was an aging-time dependent enhancement of average hydrodynamic size in TiO2 NPs stock suspensions. The cytotoxicity of fresh TiO2 NPs increased in a size-dependent manner; in contrast, their genotoxicity decreased with the increasing sizes of NPs. No significant toxicity difference was observed in cells exposed to either fresh or 60 day-aged TiO2 NPs. Both Fresh and aged TiO2 NPs efficiently induced mitochondrial dysfunction and activated Caspase-3/7 in a size-dependent manner. Using mitochondrial-DNA deficient (ρ0) AL cells, we further discovered that mitochondrial dysfunction made significant contribution to the size-dependent toxicity induced by TiO2 NPs during the aging process. Taken together, our data indicated that TiO2 NPs could significantly induced the cytotoxicity and genotoxicity in an aging time-independent and size-dependent manner, which were triggered by mitochondrial dysfunction. Our study suggested the necessity to include size as an additional parameter for the cautious monitoring of TiO2 NPs disposal before entering the environment.


Assuntos
Nanopartículas/toxicidade , Titânio/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Dano ao DNA , Humanos , Testes de Toxicidade
12.
Anticancer Res ; 39(9): 4805-4810, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519582

RESUMO

BACKGROUND/AIM: Ro 90-7501 has been reported as an inhibitor of the amyloid ß42 fibril assembly that is associated with Alzheimer's disease. The present study aimed to elucidate the radiosensitizing effects of Ro 90-7501 and focused on ATM signaling after irradiation. MATERIALS AND METHODS: Clonogenic survival, apoptosis, and cell-cycle assays as well as western blotting were performed in HeLa cells treated with irradiation and Ro 90-7501. Tumor growth delay assay was also performed using BALB/c-nu mice. RESULTS: The combination of irradiation with Ro 90-7501 showed significant radiosensitizing effects in clonogenic survival and tumor growth delay assays. Ro 90-7501 significantly increased apoptosis and impaired cell cycle after irradiation. Western blotting showed that Ro 90-7501 suppressed the phosphorylation of ATM and its downstream proteins, such as H2AX, Chk1, and Chk2, after irradiation. CONCLUSION: Ro 90-7501 inhibits DNA damage response by inhibiting ATM and has significant radiosensitizing effects on cervical cancer cells.


Assuntos
Aminas/farmacologia , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Benzimidazóis/farmacologia , Radiossensibilizantes/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Camundongos , Modelos Biológicos , Fosforilação/efeitos dos fármacos , Neoplasias do Colo do Útero/metabolismo
13.
Anticancer Res ; 39(9): 4845-4851, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519587

RESUMO

BACKGROUND/AIM: Triple-negative breast cancer (TNBC) constitutes 15-20% of all breast carcinomas, affecting younger women more often and has a worse prognosis than other types of breast cancer, due to the combination of more aggressive clinical behavior and lack of molecular targets for therapy. This study assessed the effects of non-genotoxic concentrations of tributyltin isothiocyanate (TBT-ITC) and triphenyltin isothiocyanate (TPT-ITC) on MDA-MB-231 cells. MATERIALS AND METHODS: MTT assay, comet assay, kinetic imaging and flow cytometry were used for analysis of MDA-MB-231 cells. RESULTS: The results showed that 100 nM concentration of TBT-ITC and TPT-ITC, that did not affect viability or DNA integrity, slowed-down migration by CD44 down-regulation. Moreover, both compounds demonstrated immunomodulatory properties, attenuating PD-L1 expression in MDA-MB-231 cells. CONCLUSION: TPT-ITC was more effective in down-regulating CD44 expression and reducing migration than TBT-ITC, while TBT-ITC was more potent in lowering PD-L1 expression in comparison with TPT-ITC.


Assuntos
Antineoplásicos/farmacologia , Biomarcadores Tumorais , Movimento Celular/efeitos dos fármacos , Isotiocianatos/farmacologia , Neoplasias de Mama Triplo Negativas/metabolismo , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Feminino , Humanos , Imunofenotipagem , Isotiocianatos/química , Compostos Orgânicos de Estanho/química
14.
An Acad Bras Cienc ; 91(3): e20180462, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31553365

RESUMO

This study aimed to evaluate the in vitro antiproliferative and inhibition of oxidative DNA-damage activities of n-butanol (n-BuOH) extract of Centaurea sphaerocephala. The in vitro antioxidant activity of the ethyl acetate (EtOAc) and the n-BuOH extracts of this plant were also assayed. To investigate the antioxidant potential, extracts were tested for their capacity to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH·) and to inhibit lipid peroxidation using the TBARs method. The contents of total phenolics and flavonoids were measured. Additionally, antiproliferative activity and DNA-damage inhibition of the n-BuOH extract was determined using XCELLigence RTCA instrument and photolyzing 46966 plasmid, respectively. The results exhibited that the scavenging abilities of the EtOAc extract were better than the n-BuOH extract with an IC50= 11.59 µg/mL and 16.67 µg/mL for both extracts, respectively. The phenolic and flavonoid contents were found higher in the n-BuOH and EtOAc extracts. Furthermore, our results showed that n-BuOH extract exhibited a remarkable inhibition of lipid peroxidation with an IC50 of 340.94±7.49 µg/mL and had an antiproliferative effect against Hela cells. Extracts of C. sphaerocephala showed antioxidant activity on scavenging DPPH·. In addition, the n-BuOH extract inhibited the lipid peroxidation and exhibited an antiproliferative effect against HeLa cells line (human cervix carcinoma).


Assuntos
1-Butanol/farmacologia , Acetatos/farmacologia , Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Centaurea/química , Dano ao DNA/efeitos dos fármacos , Extratos Vegetais/farmacologia , 1-Butanol/isolamento & purificação , Acetatos/isolamento & purificação , Antioxidantes/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Espectrometria de Massas
15.
J Agric Food Chem ; 67(39): 10947-10953, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31498626

RESUMO

Aflatoxins are secondary fungal metabolites that can contaminate feed and food. They are a cause of growing concern worldwide, because they are potent carcinogenic agents. Thiosemicarbazones are molecules that possess interesting antiaflatoxigenic properties, but in order to use them as crop-protective agents, their cytotoxic and genotoxic profiles must first be assessed. In this paper, a group of thiosemicarbazones and a copper complex are reported as compounds able to antagonize aflatoxin biosynthesis, fungal growth, and sclerotia biogenesis in Aspergillus flavus. The two most interesting thiosemicarbazones found were noncytotoxic on several cell lines (CRL1790, Hs27, HFL1, and U937), and therefore, they were submitted to additional analysis of mutagenicity and genotoxicity on bacteria, plants, and human cells. No mutagenic activity was observed in bacteria, whereas genotoxic activity was revealed by the Alkaline Comet Assay on U937 cells and by the test of chromosomal aberrations in Allium cepa.


Assuntos
Aflatoxinas/metabolismo , Antifúngicos/farmacologia , Aspergillus flavus/efeitos dos fármacos , Produtos Agrícolas/microbiologia , Dano ao DNA/efeitos dos fármacos , Doenças das Plantas/prevenção & controle , Tiossemicarbazonas/farmacologia , Aspergillus flavus/genética , Aspergillus flavus/crescimento & desenvolvimento , Aspergillus flavus/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Doenças das Plantas/microbiologia
16.
Chem Commun (Camb) ; 55(76): 11414-11417, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31482872

RESUMO

Herein we present an assay allowing concurrent detection of oxidative DNA damage and photoproducts. We apply DNA repair enzymes specific for each lesion type to incorporate spectrally distinct fluorescent nucleotides, enabling simultaneous quantification of the lesions on individual DNA molecules. We follow the repair of both damage types in skin cells exposed to artificial sunlight.


Assuntos
Cor , Dano ao DNA , DNA/química , Corantes Fluorescentes/química , Raios Ultravioleta , Reparo do DNA , Células HEK293 , Humanos , Oxirredução
17.
Chem Biol Interact ; 312: 108814, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31509734

RESUMO

Nanotechnology is a growing science that may provide several new applications for medicine, food preservation, diagnostic technologies, and sanitation. Despite its beneficial applications, there are several questions related to the safety of nanomaterials for human use. The development of nanotechnology is associated with some concerns because of the increased risk of carcinogenesis following exposure to nanomaterials. The increased levels of reactive oxygen species (ROS) that are due to exposure to nanoparticles (NPs) are primarily responsible for the genotoxicity of metal NPs. Not all, but most metal NPs are able to directly produce free radicals through the release of metal ions and through interactions with water molecules. Furthermore, the increased production of free radicals and the cell death caused by metal NPs can stimulate reduction/oxidation (redox) reactions, leading to the continuous endogenous production of ROS in a positive feedback loop. The overexpression of inflammatory mediators, such as NF-kB and STATs, the mitochondrial malfunction and the increased intracellular calcium levels mediate the chronic oxidative stress that occurs after exposure to metal NPs. In this paper, we review the genotoxicity of different types of metal NPs and the redox mechanisms that amplify the toxicity of these NPs.


Assuntos
Nanopartículas Metálicas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Cálcio/metabolismo , Dano ao DNA/efeitos dos fármacos , Aditivos Alimentares/química , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Neoplasias/tratamento farmacológico , Oxirredução , Espécies Reativas de Oxigênio/metabolismo
18.
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
19.
Chem Commun (Camb) ; 55(79): 11944-11947, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31531457

RESUMO

A novel hexanuclear copper(ii)-based complex, [Cu6(tpbb)2(NO3)12] (1), was synthesized, which shows potent cytotoxicity to hepatoma carcinoma cells by inducing apoptosis and apoptosis-related processes. Furthermore, mechanistic investigations based on proteomes revealed that the induced apoptosis was mediated by acting on several targets and multiple pathways in a pleiotropic way.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Complexos de Coordenação/química , Cobre/química , Neoplasias Hepáticas/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Dano ao DNA/efeitos dos fármacos , Desenho de Drogas , Humanos , Ligantes , Neoplasias Hepáticas/patologia , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade
20.
Chemosphere ; 235: 1116-1124, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31561302

RESUMO

The porous graphitic carbon nitride nanosheets (PCNSs) with high yields were synthesized by using one-step chemical exfoliation method. PCNSs accelerated separation efficiency of photo-generated electron-hole pairs in comparison to bulk graphitic carbon nitride. The PCNS5 (exfoliation for 5 h) exhibited optimal photocatalytic disinfection capability towards Escherichia coli K-12 under simulated solar light irradiation with complete disinfection of 6.5 log10 cfu/mL of E. coil K-12 within 2 h. The enhanced photocatalytic activity of PCNS5 originated from mesoporous nanosheet structure. The possible mechanism of photocatalytic disinfection has proposed that intracellular reactive oxygen species levels and the activities of antioxidant enzymes (e.g., catalase and superoxide dismutase) were enhanced. Transmission electron microscope images observed during photocatalytic disinfection process suggested that the cell membrane was regarded as the first target for oxidation, resulting in a faster leakage of cytoplasmic content and finally degradation of DNA leading to bacterial death. Furthermore, the trapping experiment showed that superoxide radical (•O2-) and holes (h+) were responsible for E. coli K-12 disinfection by PCNS5.


Assuntos
Desinfecção/métodos , Escherichia coli K12/efeitos dos fármacos , Nanoestruturas/química , Nitrilos/toxicidade , Fotólise , Bactérias/efeitos dos fármacos , Membrana Celular/metabolismo , Dano ao DNA , Oxirredução , Porosidade , Espécies Reativas de Oxigênio
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