RESUMO
BACKGROUND: Artemis deficiency is an autosomal recessive disorder characterized by a combined immunodeficiency with increased cellular radiosensitivity. In this review, the clinical and genetic characteristics of 15 patients with DCLRE1C variants are presented. METHODS: The demographic, clinical, immunologic, and genetic characteristics of patients with confirmed DCLRE1C variants diagnosed between 2013 and 2023 were collected retrospectively. Three patients were evaluated for radiosensitivity by the Comet assay, compared with age- and sex-matched healthy control. RESULTS: Seven patients who had severe infections in the first 6 months of life were diagnosed with T-B-NK+ SCID (severe combined immunodeficiency). Among them, four individuals underwent transplantation, and one of those died due to post-transplant complications in early life. Eight patients had hypomorphic variants. Half of them were awaiting a suitable donor, while the other half had already undergone transplantation. The majority of patients were born into a consanguineous family (93.3%). Most patients had recurrent sinopulmonary infections (73.3%), and one patient had no other infection than an acute respiratory infection before diagnosis. Two patients (13.3%) had autoimmunity in the form of autoimmune hemolytic anemia. Growth retardation was observed in only one patient (6.6%), and no malignancy was detected in the surviving 11 patients during the median (IQR) of 21.5 (12-45) months of follow-up. Three patients who had novel variants exhibited increased radiosensitivity and compromised DNA repair, providing a potential vulnerability to malignant transformation. CONCLUSION: Early diagnosis, radiation avoidance, and careful preparation for transplantation contribute to minimizing complications, enhancing life expectancy, and improving the patient's quality of life.
Assuntos
Proteínas de Ligação a DNA , Tolerância a Radiação , Imunodeficiência Combinada Severa , Humanos , Tolerância a Radiação/genética , Masculino , Feminino , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/terapia , Lactente , Proteínas de Ligação a DNA/genética , Pré-Escolar , Estudos Retrospectivos , Endonucleases/genética , Proteínas Nucleares/genética , Criança , Estudos de CoortesRESUMO
STAT3 plays an important role in various complex and sometimes contradictory pathways such as proliferation, differentiation, migration, inflammation, and apoptosis. The transcriptional activity of the STAT3 gene is controlled by a transcription factor called ZNF341. There is insufficient data on radiation sensitivity and post-radiation DNA repair in STAT3- loss-of-function (LOF) patients. We aimed to investigate the radiosensitivity in patients with STAT3-LOF and ZNF341 deficiency. Twelve patients with STAT3-LOF and four ZNF341-deficiency patients were recruited from three clinical immunology centers in Turkey and evaluated for radiosensitivity by the Comet assay, comparing to 14 age- and sex-matched healthy controls. The tail length (TL) (µm), percentage of DNA in the tail (TDNA%), and olive tail moment (OTM) (arbitrary units) were evaluated at the same time for baseline (spontaneous), initial (immediately after 2 Gy irradiation), and recovery (2 h after irradiation) periods by using a computerized image-analysis system, estimating DNA damage. Except for a patient with ZNF341 deficiency who developed nasal cell primitive neuroendocrine tumor and papillary thyroid cancer during the follow-up, there was no cancer in both groups. During the recovery period of irradiation, TL, TDNA%, and OTM values of healthy controls decreased rapidly toward the baseline, while these values of patients with STAT3-LOF and ZNF341 deficiency continued to increase, implying impaired DNA repair mechanisms. Increased radiosensitivity and impaired DNA repair were demonstrated in patients diagnosed with STAT3-LOF and ZNF341 deficiency, potentially explaining the susceptibility to malignant transformation.
Assuntos
Reparo do DNA , Tolerância a Radiação , Fator de Transcrição STAT3 , Fatores de Transcrição , Ensaio Cometa , Dano ao DNA/genética , Reparo do DNA/genética , Regulação da Expressão Gênica , Humanos , Mutação com Perda de Função , Tolerância a Radiação/genética , Fator de Transcrição STAT3/genética , Fatores de Transcrição/genéticaAssuntos
Síndrome de Job/diagnóstico , Mutação/genética , Neoplasias Nasofaríngeas/diagnóstico , Câncer Papilífero da Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Fatores de Transcrição/genética , Adulto , Consanguinidade , Feminino , Humanos , Síndrome de Job/genética , Neoplasias Nasofaríngeas/genética , Fator de Transcrição STAT3/metabolismo , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Ativação TranscricionalRESUMO
The aim of this study was to investigate the effects of water soluble fullerene (fullerenol) nanoparticles on the in vitro genotoxicity induced by the insecticide acetamiprid. Healthy human lung cells (IMR-90) were treated with fullerenol C60(OH)n (n: 18-22) alone and in combination with acetamiprid for 24h. The micronucleus test, comet assay and γ-H2AX foci formation assays were used as genotoxicity endpoints. Cytotoxicity was evaluated using the clonogenic assay. The maximum tested concentration of fullerenol (1.600 µg/ml) induced 77% survival where as the lowest concentration (25 µg/ml) was not cytotoxic where as acetamiprid was cytotoxic. Fullerenol did not induce genotoxicity at tested concentrations (50-1600 µg/L). On the other hand, acetamiprid (>50 µM) significantly induced formation of micronuclei, and double and single stranded DNA breaks in IMR-90 cells. For simultaneous exposure studies, two non-cytotoxic concentrations (50 and 200 µg/ml) of fullerenol and three cytotoxic concentrations of acetamiprid (100, 200 and 400 µM) were selected. As a result, we observed that co-exposure with fullerenol significantly reduced the cytotoxicity and genotoxicity of acetamiprid in IMR-90 cells. Our results indicated the protective effect of water soluble fullerene particles on herbicide induced genotoxicity.
Assuntos
Fulerenos/farmacologia , Inseticidas/toxicidade , Mutagênicos/toxicidade , Nanopartículas/toxicidade , Substâncias Protetoras/farmacologia , Piridinas/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Fibroblastos/efeitos dos fármacos , Histonas/metabolismo , Humanos , Pulmão/citologia , Testes para Micronúcleos , NeonicotinoidesRESUMO
Esbiothrin, synthetic pyrethroid with quick activity against insects, is widely used against household pests and in public health. Despite widespread use, data on ecotoxicity and genotoxic effects are extremely scarce. The aim of the present study is to evaluate the genotoxic potential of esbiothrin on a model fish species Cyprinus carpio L., 1758 (Pisces: Cyprinidae, koi) using the micronucleus test and comet assay in peripheral blood erythrocytes. Effects of two sublethal exposure concentrations on plasma total antioxidant status (TAS mmol/L), and Hct values were examined. On the basis of the 96 h LC50 data from U.S. EPA ecotox database (32 µg/L) two sublethal exposure concentrations (5 and 10 µg/L) were used together with ethyl methanesulfonate (EMS) (5 mg/L) as positive control. Five fish were used for each dose/duration group (24, 48, and 72 h) under controlled laboratory conditions. The fish showed behavioral changes at the higher dose. Plasma TAS (mmol/L) levels decreased in 24 h; an increase was observed slightly for 48 and obviously for 72 h in both exposure doses. Similarly, hematocrit (Hct) values differed between exposure duration but no significant differences in mean values were found between groups of the same exposure time. The general trend was a rise after 48 h, which decreased afterwards. Our results revealed significant increases in the frequencies of micronuclei and levels of DNA strand breaks and thus demonstrated the genotoxic potential of this pesticide on fish, a nontarget organism of the aquatic ecosystem. To our knowledge this is the first study to report observable genotoxic effects of esbiothrin on fish.
Assuntos
Aletrinas/análogos & derivados , Antioxidantes/metabolismo , Carpas/metabolismo , Inseticidas/toxicidade , Aletrinas/toxicidade , Animais , Carpas/genética , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Testes para MicronúcleosRESUMO
The genotoxic effects of mercury chloride and lead acetate were evaluated in vivo using the micronucleus (MN) assay on acridine-orange (AO) stained peripheral blood erythrocytes, gill and fin epithelial cells of Carassius auratus auratus. Fish were exposed to three different concentrations of mercury chloride (MC) (1 microg/, 5 microg/L and 10 microg/L) and lead acetate (LA) (10 microg/L, 50 microg/L and 100 microg/L) for 2, 4 and 6 days. A single dose of 5 mg/L cyclophosphamide was used as a positive control. In addition to micronuclei, nuclear buds (NBs) were assessed in the erythrocytes. The ratio of polychromatic and normochromatic erythrocytes (PCE/NCE) in peripheral blood was also evaluated to assess cytotoxicity. MN frequencies in all three tissues were elevated in fish exposed to both LA and MC. However, NBs showed different sensitivity to metal treatments. MN frequencies in both control and treated fish were highest in gill cells and generally lower in erythrocytes and fin cells. PCE/NCE rations decreased in relation to MC and LA treatments. The results of this study indicate that LA and MC have genotoxic and cytotoxic damage in fish and confirmed that AO staining is a suitable technique for in vivo MN test in fish.
Assuntos
Carpa Dourada/fisiologia , Cloreto de Mercúrio/toxicidade , Mutagênicos/toxicidade , Compostos Organometálicos/toxicidade , Laranja de Acridina , Animais , Corantes Azur , Células Cultivadas , Eritrócitos/efeitos dos fármacos , Brânquias/citologia , Brânquias/efeitos dos fármacos , Testes para Micronúcleos , Microscopia de FluorescênciaRESUMO
The aim of the study was to evaluate the toxic and mutagenic effects of bottled purified and natural spring waters for drinking. The study presents the genotoxicologic results of drinking water samples packaged in polyethylene terephthalate (PET) bottles. Genotoxic agents have the potential to interact with DNA and may cause DNA damage. Endpoints analyzed included mitotic index (MI), replication index (RI), and sister chromatid exchange (SCE). An analysis of variance test (ANOVA) was performed to evaluate the results. A significant decrease in MI and RI was observed compared with negative control cultures, respectively, (p<0.05, p<0.01). It is found that SCE frequency increases compared with negative control. There is no significant difference between negative control and drinking water samples and among drinking water samples for sister chromatid exchange induction (p>0.05).
Assuntos
Dano ao DNA/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Mutagênicos/toxicidade , Polietilenotereftalatos/toxicidade , Troca de Cromátide Irmã/efeitos dos fármacos , Água/química , Análise de Variância , Proliferação de Células , Células Cultivadas , Relação Dose-Resposta a Droga , Embalagem de Alimentos , Humanos , Águas Minerais/toxicidade , Índice Mitótico , Testes de MutagenicidadeRESUMO
The Berdan River, which empties into the Mediterranean Sea on the east coast of Turkey, receives discharges of industrial and municipal waste. In the present study, the in vivo piscine micronucleus (MN) test was used to evaluate the genotoxicity of water samples collected from different locations along the Berdan River. Nile tilapia (Oreochromis niloticus) were exposed in the laboratory for 2, 4, and 6 days, and micronuclei were evaluated in peripheral blood erythrocytes, gill cells, and caudal fin epithelial cells. A single dose of 5 mg/L cyclophosphamide was used as a positive control. In addition to micronuclei, nuclear abnormalities (NAs), such as binucleated cells and blebbed, notched, and lobed nuclei, were assessed in the erythrocytes, and chemical analyses were carried out to determine the amount of heavy metals in the water samples. MN and NA frequencies were significantly elevated (up to 2- to 3-fold) in fish exposed to river water samples taken downstream of potential discharges, and the elevated responses in gill and fin cells were related to the concentration of heavy metals in the water. MN frequencies (expressed as micronucleated cells/1,000 cells), in both treated and untreated fish, were greatest in gill cells (range: 0.80-3.70), and generally lower in erythrocytes (range: 0.50-2.80), and fin cells (range: 0.45-1.70). The results of this study indicate that the Berdan River is contaminated with genotoxic pollutants and that the genotoxicity is related to the discharge of wastes into the river water.
Assuntos
Monitoramento Ambiental , Peixes/genética , Rios/química , Testes de Toxicidade , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Animais , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Geografia , Brânquias/citologia , Testes para Micronúcleos , TurquiaRESUMO
Pesticides are widely used throughout the world in agriculture to protect crops and in public health to control diseases. Nevertheless, exposure to pesticides represents a potential risk to humans. This paper describes a study of possible genetic damage in the people living in regions contaminated with complex mixture of pesticides in Göksu Delta. In this study, used methods were chromosomal aberration (CA), sister chromatid exchange analysis (SCE) in the peripheral blood lymphocytes, and micronucleus (MN) assay in the buccal epithelial cells. In the present investigation, 32 affected subjects consist of 16 smoking and 16 non-smokings and an equal number of control subjects were assessed for genome damage. Micronucleus (MN), Broken egg (BE), Karyorrhexis (KR), Karyolysis (KL) and Binucleus (BN) frequencies were higher in affected subjects than in controls. Smoking had a statistically significant effect on the Micronucleus, Karyorrhexis and Binucleus frequencies for both the control and the exposed group. Also smoking and exposure affected the frequency of sister chromatid exchange and chromosomal aberrations compared with control groups.
Assuntos
Aberrações Cromossômicas , Monitoramento Ambiental/métodos , Micronúcleos com Defeito Cromossômico , Praguicidas/toxicidade , Troca de Cromátide Irmã , Biomarcadores/análise , Células Cultivadas , Feminino , Humanos , Linfócitos/sangue , Linfócitos/efeitos dos fármacos , Masculino , Testes para Micronúcleos/métodos , Mucosa Bucal/efeitos dos fármacos , Testes de Mutagenicidade , Exposição Ocupacional/efeitos adversos , Fumar/efeitos adversos , Áreas AlagadasRESUMO
To evaluate the use of native fish species for assessing genotoxic pollution in the marine environment, micronucleus (MN) analysis was performed in peripheral blood erythrocytes and gill cells of the grey mullet (Mugil cephalus) from three sampling stations off the southeastern Mediterranean coast of Turkey. The frequencies of blebbed, notched, and lobed nuclei and binucleated cells also were evaluated in peripheral erythrocytes. The sampling sites were chosen on the basis of pollution levels; Karaduvar harbor, contaminated by different types of industrial effluents, and Mersin harbor, mainly contaminated by aromatic hydrocarbons, were selected as polluted areas. Erdemli harbor, a relatively unpolluted site, was used as the control area. Sampling was carried out at four different seasons. The frequencies of both micronuclei and other nuclear abnormalities (NAs) in mullets captured from polluted areas were significantly higher than those in mullets from the reference area. In general, gill cells had considerably higher MN frequencies than did erythrocytes, and genotoxic responses were higher in summer than in winter. The results of this study indicate that the MN test in fish is a suitable biomarker for in situ monitoring of genotoxic pollution in the marine environment. As demonstrated in this study, NAs other than micronuclei are also useful indices of chemical exposure and toxic responses. Therefore, measuring both micronuclei and NAs may increase the sensitivity of the test system.
Assuntos
Monitoramento Ambiental/métodos , Eritrócitos/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Mutagênicos/toxicidade , Smegmamorpha/sangue , Poluentes Químicos da Água/toxicidade , Animais , Bioensaio , Mar Mediterrâneo , Testes para MicronúcleosRESUMO
Common carp (Cyprinus carpio), Prussian carp (Carassius gibelio) and Peppered cory (Corydoras paleatus) were evaluated as target species to perform genotoxicity tests for heavy metals. Fishes were exposed to different doses of cadmium (0.005-0.1 mg/L) and copper (0.01-0.25 mg/L) for 21 days. Hexavalent chromium at a single dose of 5 mg/L was used as a positive control. Frequencies of micronuclei and binuclei were evaluated comparatively in peripheral blood erythrocytes, gill epithelial cells and liver cells. As a result it was observed that, fish species and their tissues showed differential sensitivity to the heavy metal treatment. In general, frequencies of micronucleated and binucleated cells significantly increased following the exposure for 21 days to copper, cadmium and chromium. On the other hand, gill and liver cells showed higher frequencies of micronuclei and binuclei than erythrocytes. Our results indicated the formation of micronuclei and binuclei in fish cells caused by their exposure to cadmium, copper and chromium, thus verifying results obtained earlier on mammals, which indicated that these heavy metals have cytotoxic and genotoxic effects. The suitability of the micronucleus assay in native fish species for the screening of aquatic genotoxicants is highlighted and the importance of target tissue selection in the piscine micronucleus test is emphasized.
Assuntos
Cádmio/toxicidade , Carpas/fisiologia , Cobre/toxicidade , Poluentes da Água/toxicidade , Animais , Antídotos/toxicidade , Cloreto de Cádmio/toxicidade , Carcinógenos Ambientais/toxicidade , Cromo/toxicidade , Sulfato de Cobre/toxicidade , Eritrócitos , Brânquias/patologia , Fígado/patologia , Testes para Micronúcleos , Testes de ToxicidadeRESUMO
The genotoxic effects of effluents from a petroleum refinery and a chromium processing plant were evaluated in Oreochromis niloticus (Pisces: Perciformes) using the micronucleus test. Fish were exposed to different concentrations (5, 10 and 20%, v/v) of the effluents for 3, 6 and 9 days. Micronucleus analyses were carried out on gill epithelial cells and peripheral blood erythrocytes. Nuclear abnormalities other than micronuclei, considered as genetic damage indicators, were also evaluated on erythrocytes. Cyclophosphamide at a single dose of 4 mg/L was used as a positive control. The results of this study showed that both effluents had genotoxic potential. On the other hand, the level of genetic damage induced by petroleum refinery effluent was considerably higher than that of chromium processing plant effluent. Our results further indicate that nuclear abnormalities other than micronuclei, such as blebbed and lobed nuclei, may also be used as indicators of genotoxic damage.
Assuntos
Cromo/toxicidade , Ciclídeos , Células Epiteliais/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Brânquias/citologia , Petróleo/toxicidade , Poluentes Químicos da Água/toxicidade , Análise de Variância , Animais , Núcleo Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Testes para Micronúcleos , TurquiaRESUMO
In this study, genotoxic potential of metronidazole, an antibiotic-antiparasitic agent widely used both clinical and veterinary areas, was evaluated using the piscine micronucleus test. Specimens of Oreochromis niloticus (Pisces: Cichlidae) were exposed to different concentrations (5, 10, 15mg/L) of metronidazole and 4mg/L cyclophosphamide (as positive control) for 24, 48 and 72h. A fluorescent staining technique with acridine orange (AO) was performed to improve the sensitivity of erythrocyte micronucleus assay with fish. AO selectively stains newly formed immature erythrocytes (PCEs) therefore allows to obtain more sensitive results by detection of the micronucleated PCEs differed than mature erythrocytes (NCEs) by their RNA-containing cytoplasm. The ratio of PCE/NCE in peripheral blood was also evaluated to assess cytotoxicity. As a result, it was observed that the frequencies of micronucleated PCEs increased both dose and time dependently while PCE/NCE ratios decreased. Our results revealed that metronidazole has cytotoxic and genotoxic effects on fish. The use of acridine orange staining technique also seems useful in assessment of short-term genotoxic effects of chemicals, when fish are used as experimental animal.
RESUMO
Binary and ternary water soluble copper(II) complexes - [Cu(nphen)2(H2O)](NO3)2·H2O (1), [Cu(phen)2(H2O)](NO3)2 (2), [Cu(nphen)(l-tyr)(H2O)]NO3·2H2O (3), [Cu(phen)(tyr)(H2O)] NO3·2H2O (4) - and diquarternary salts of nphen and phen (nphen=5-nitro-1,10-phenanthroline, phen=1,10-phenanthroline and tyr=l-tyrosine) have been synthesized and characterized by CHN analysis, (1)H NMR, (13)C NMR and IR spectroscopy, thermal analysis and single crystal X-ray diffraction techniques. The CT-DNA binding properties of these compounds have been investigated by thermal denaturation measurements, absorption and emission spectroscopy. The supercoiled pUC19 plasmid DNA cleavage activity of these compounds has been explored by agarose gel electrophoresis. The cytotoxicity of these compounds against MCF-7, Caco-2, A549 cancer cells and BEAS-2B healthy cells was also studied by using XTT method. The complexes 1-4 exhibit significant high cytotoxicity with low IC50 values in compared with cisplatin. The effect of the substituents of phen and coordinated amino acid in the above complexes are presented and discussed.
Assuntos
DNA/metabolismo , Fenantrolinas/metabolismo , Fenantrolinas/toxicidade , Tirosina/metabolismo , Água/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cristalografia por Raios X , DNA/química , Clivagem do DNA/efeitos dos fármacos , Eletroforese em Gel de Ágar , Humanos , Concentração Inibidora 50 , Ligantes , Conformação Molecular , Desnaturação de Ácido Nucleico/efeitos dos fármacos , Fenantrolinas/química , Solubilidade , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Temperatura , Tirosina/químicaRESUMO
Micronucleus formation in fish erythrocytes, as an indicator of chromosomal damage, has been increasingly used to detect the genotoxic potential of environmental contaminants. Nucleolar organizer regions (NORs) stained with colloidal silver techniques indicate sites of active RNA transcription. The number and size of NORs in interphase nuclei reflect cellular activities such as proliferation and differentiation of cells. In this study, nuclear (micronucleus frequency) and nucelolar (changes in quantitative characteristics of nucleoli) biomarkers were used to evaluate the functional and structural genotoxic effects of the pyrethroid insecticide lambda-cyhalothrin on Garra rufa (Pisces: Cyprinidae). The frequency of micronuclei was examined in blood smears obtained from fishes exposed to three different concentrations (0.005, 0.01, 0.05 microg/l) for a period of 36 h. Nucleolar parameters (the average number of nucleoli per cell; the volume of a single nucleolus; and the percentage of cells with heteromorphic paired nucleoli) were examined in epithelial cells obtained from the edge of caudal fins at the 90th and 180th minutes of exposure. Results of both tests demonstrated the genotoxic potential of pyrethroid lambda-cyhalothrin on G. rufa. The frequency of micronucleated erythrocytes was significantly increased while the nucleolar parameters were repressed by lambda-cyhalothrin treatment. Our results confirmed that the use of nucleolar biomarkers on fish fin cells, in addition to micronucleus test, could provide valuable information in aquatic genotoxicity studies.
Assuntos
Biomarcadores/análise , Nucléolo Celular/efeitos dos fármacos , Cyprinidae/genética , Inseticidas/toxicidade , Testes de Mutagenicidade/métodos , Piretrinas/toxicidade , Animais , Testes para Micronúcleos , NitrilasRESUMO
In this study, cyto-genotoxic effects of a textile mill effluent on fish Oreochromis niloticus were investigated using the micronucleus (MN) test and methods to analyze interphase silver-stained nucleolar organizer regions (AgNORs). Fishes were exposed to three different concentrations of textile mill effluent (5, 10 and 20%(v/v)) for 3, 6 and 9 days. Cyclophosphamide (2mg/l) was used as a positive control. Micronucleus frequencies were examined in peripheral blood erythrocytes and gill cells. Nuclear abnormalities (NA) other than micronuclei such as binuclei, lobed nuclei, blebbed nuclei and notched nuclei were also evaluated in peripheral erythrocytes. Interphase AgNOR parameters were examined in epithelial cells obtained from the edge of caudal fins after 90 and 180min of exposure. As a result, dose-dependent increases in the frequencies of micronuclei and other NA in erythrocytes were observed. MN frequencies in gill cells also significantly increased, while the interphase AgNOR parameters in fin cells decreased, as a result of textile effluent and cylophosphamide treatments.
Assuntos
Ciclídeos , Monitoramento Ambiental/métodos , Mutagênicos/toxicidade , Região Organizadora do Nucléolo/efeitos dos fármacos , Indústria Têxtil , Poluentes Químicos da Água/toxicidade , Animais , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/genética , Núcleo Celular/patologia , Relação Dose-Resposta a Droga , Eritrócitos/efeitos dos fármacos , Eritrócitos/patologia , Interfase/efeitos dos fármacos , Interfase/genética , Testes para Micronúcleos , Região Organizadora do Nucléolo/genética , Coloração pela PrataRESUMO
In this study, cytogenetic analysis of Gobius paganellus, a Mediterranean Gobiid fish from the southern coast of Turkey, was carried out by modified air-dried technique. Phytohemaglutinine pretreatment was performed before the conventional air-dried technique to increase the mitotic index. Chromosomes were obtained using gill tissue. As a result, it was determined that the diploid chromosome number of Gobius paganellus is 2n = 44 (NF = 45), comprising one large metacentric and 43 acrocentric chromosomes.
Assuntos
Cromossomos/genética , Perciformes/genética , Animais , Cariotipagem , TurquiaRESUMO
In the present study, in vitro cytotoxic and genotoxic effect of copper-zinc alloy nanoparticles (Cu-Zn ANPs) on human lung epithelial cells (BEAS-2B) were investigated. XTT test and clonogenic assay were used to determine cytotoxic effects. Cell death mode and intracellular reactive oxygen species formations were analyzed using M30, M65 and ROS Elisa assays. Genotoxic effects were evaluated using micronucleus, comet and γ-H2AX foci assays. Cu-Zn ANPs were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential measurements. Characterization of Cu-Zn ANPs showed an average size of 200nm and zeta potential of -22mV. TEM analyses further revealed the intracellular localization of Cu-Zn ANPs in cytoplasm within 24h. Analysis of micronucleus, comet and γ-H2AX foci counts showed that exposure to Cu-Zn ANPs significantly induced chromosomal damage as well as single and double stranded DNA damage in BEAS-2B cells. Our results further indicated that exposure to Cu-Zn ANPs significantly induced intracellular ROS formation. Evaluation of M30:M65 ratios suggested that cell death was predominantly due to necrosis.
Assuntos
Testes de Carcinogenicidade , Cobre/química , Pulmão/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Testes de Mutagenicidade , Zinco/química , Apoptose , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Técnicas In Vitro , Pulmão/citologia , Pulmão/metabolismo , Microscopia Eletrônica de Transmissão , Espécies Reativas de Oxigênio/metabolismoRESUMO
The present study was designed to determine the protective activity of cinnamic acid against induction by X-rays of genomic instability in normal human blood lymphocytes. This radio-protective activity was assessed by use of the cytokinesis-block micronucleus test and the alkaline comet assay, with human blood lymphocytes isolated from two healthy donors. A Siemens Mevatron MD2 (Siemens AG, USA, 1994) linear accelerator was used for the irradiation with 1 or 2 Gy. Treatment of the lymphocytes with cinnamic acid prior to irradiation reduced the number of micronuclei when compared with that in control samples. Treatment with cinnamic acid without irradiation did not increase the number of micronuclei and did not show a cytostatic effect in the lymphocytes. The results of the alkaline comet assay revealed that cinnamic acid reduces the DNA damage induced by X-rays, showing a significant radio-protective effect. Cinnamic acid decreased the frequency of irradiation-induced micronuclei by 16-55% and reduced DNA breakage by 17-50%, as determined by the alkaline comet assay. Cinnamic acid may thus act as a radio-protective compound, and future studies may focus on elucidating the mechanism by which cinnamic acid offers radioprotection.
Assuntos
Cinamatos/farmacologia , Instabilidade Genômica/efeitos da radiação , Linfócitos/efeitos da radiação , Fenóis/farmacologia , Compostos Fitoquímicos/farmacologia , Raios X/efeitos adversos , Adulto , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Relação Dose-Resposta à Radiação , Feminino , Humanos , Linfócitos/efeitos dos fármacos , Masculino , Testes para Micronúcleos , Protetores contra Radiação/farmacologiaRESUMO
The present study was designed to determine the radioprotective effect of two phytochemicals, namely, quinic acid and chlorogenic acid, against X-ray irradiation-induced genomic instability in non-tumorigenic human blood lymphocytes. The protective ability of two phenolic acids against radiation-induced DNA damage was assessed using the alkaline comet assay in human blood lymphocytes isolated from two healthy human donors. A Siemens Mevatron MD2 (Siemens AG, USA, 1994) linear accelerator was used for irradiation. The results of the alkaline comet assay revealed that quinic acid and chlorogenic acid decreased the DNA damage induced by X-ray irradiation and provided a significant radioprotective effect. Quinic acid decreased the presence of irradiation-induced DNA damage by 5.99-53.57% and chlorogenic acid by 4.49-48.15%, as determined by the alkaline comet assay. The results show that quinic acid and chlorogenic acid may act as radioprotective compounds. Future studies should focus on determining the mechanism by which these phenolic acids provide radioprotection.