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Dano ao DNA , Vidro , Exposição Ocupacional , Exposição Ocupacional/efeitos adversos , Humanos , Vidro/químicaRESUMO
Oxidative stress and sterile inflammation play roles in the induction and maintenance of metabolic syndrome (MetS). This study cohort included 170 females aged 40 to 45 years who were categorized according to the presentation of MetS components (e.g., central obesity, insulin resistance, atherogenic dyslipidemia, and elevated systolic blood pressure) as controls not presenting a single component (n = 43), those with pre-MetS displaying one to two components (n = 70), and females manifesting MetS, e.g., ≥3 components (n = 53). We analyzed the trends of seventeen oxidative and nine inflammatory status markers across three clinical categories. A multivariate regression of selected oxidative status and inflammatory markers on the components of MetS was performed. Markers of oxidative damage (malondialdehyde and advanced-glycation-end-products-associated fluorescence of plasma) were similar across the groups. Healthy controls displayed lower uricemia and higher bilirubinemia than females with MetS; and lower leukocyte counts, concentrations of C-reactive protein, interleukine-6, and higher levels of carotenoids/lipids and soluble receptors for advanced glycation end-products than those with pre-MetS and MetS. In multivariate regression models, levels of C-reactive protein, uric acid, and interleukine-6 were consistently associated with MetS components, although the impacts of single markers differed. Our data suggest that a proinflammatory imbalance precedes the manifestation of MetS, while an imbalance of oxidative status accompanies overt MetS. Further studies are needed to elucidate whether determining markers beyond traditional ones could help improve the prognosis of subjects at an early stage of MetS.
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As part of a large human biomonitoring study, we conducted occupational monitoring in a glass fibre factory in Slovakia. Shopfloor workers (n = 80), with a matched group of administrators in the same factory (n = 36), were monitored for exposure to glass fibres and to polycyclic aromatic hydrocarbons (PAHs). The impact of occupational exposure on chromosomal aberrations, DNA damage and DNA repair, immunomodulatory markers, and the role of nutritional and lifestyle factors, as well as the effect of polymorphisms in metabolic and DNA repair genes on genetic stability, were investigated. The (enzyme-modified) comet assay was employed to measure DNA strand breaks (SBs) and apurinic sites, oxidised and alkylated bases. Antioxidant status was estimated by resistance to H2O2-induced DNA damage. Base excision repair capacity was measured with an in vitro assay (based on the comet assay). Exposure of workers to fibres was low, but still was associated with higher levels of SBs, and SBs plus oxidised bases, and higher sensitivity to H2O2. Multivariate analysis showed that exposure increased the risk of high levels of SBs by 20%. DNA damage was influenced by antioxidant enzymes catalase and glutathione S-transferase (measured in blood). DNA repair capacity was inversely correlated with DNA damage and positively with antioxidant status. An inverse correlation was found between DNA base oxidation and the percentage of eosinophils (involved in the inflammatory response) in peripheral blood of both exposed and reference groups. Genotypes of XRCC1 variants rs3213245 and rs25487 significantly decreased the risk of high levels of base oxidation, to 0.50 (p = 0.001) and 0.59 (p = 0.001), respectively. Increases in DNA damage owing to glass fibre exposure were significant but modest, and no increases were seen in chromosome aberrations or micronuclei. However, it is of concern that even low levels of exposure to these fibres can cause significant genetic damage.
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Antioxidantes , Exposição Ocupacional , Humanos , Monitoramento Biológico , Peróxido de Hidrogênio , Dano ao DNA , Reparo do DNA , Ensaio Cometa , Exposição Ocupacional/efeitos adversos , Aberrações Cromossômicas , DNA , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
OBJECTIVES: Due to nano-dimensions (less than 100 nm), can nanoparticles probably penetrate through various membranes and travel from the bloodstream to other organs in the body. The aim of our study was to find out whether NPs Fe3O4 (coated with sodium oleate) injected into the tail vein of laboratory Wistar rats pass through the bloodstream to the respiratory tract (in comparison with a control group); and if so whether increasing doses of NPs Fe3O4 have an escalating harmful effect on selected bronchoalveolar lavage (BAL) parameters. METHODS: Wistar rats were intravenously given 3 doses of the suspension of NPs Fe3O4 (0.1% LD50 = 0.0364, 1.0% = 0.364 and 10.0% = 3.64 mg/kg animal body weight). Seven days later, we sacrificed the animals under anaesthesia, performed bronchoalveolar lavage (BAL), and isolated the collected cells. Many inflammatory and cytotoxic BAL parameters were examined. RESULTS: Both inflammatory and cytotoxic BAL parameters affected by Fe3O4 suspension were changed compared to control results, but not all were statistically significant. Thus, the NPs Fe3O4 passed through the bloodstream to the respiratory tract and affected it. The highest concentration of NPs Fe3O4 (10%) had the most influence on BAL parameters (7 of 12 parameters). Only 3 parameters showed a pure dose dependence. CONCLUSION: We assume that the adverse effect of Fe3O4 NPs in our study is probably not correlated with the dose, but rather with the size of the particles or with their surface area.
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Óxido Ferroso-Férrico , Nanopartículas , Ratos , Animais , Ratos Wistar , Lavagem Broncoalveolar , Administração Intravenosa , Líquido da Lavagem BroncoalveolarRESUMO
Cow's milk allergy (CMA) is one of the most frequent types of food allergy. The aim of the study was to investigate whether IL-13 R130Q and IL-4 T589C polymorphisms are associated with the risk of CMA in young Ukrainian children. A total of 120 children (age range: 1−3 years) participated in the study and were divided into two groups: CMA (n = 60) and healthy controls (CNT, n = 60). The CMA group had two subgroups: specific oral tolerance induction (SOTI, n = 30) and milk elimination diet (MED, n = 30). The CNT group had two subgroups: positive family history of allergy (+FHA, n = 24) and negative family history of allergy (−FHA, n = 36). In the CMA group, molecular genetic testing of CC, CT, and TT genotypes of single nucleotide IL-4 T589C gene polymorphisms showed significantly higher rates of the CC genotype compared to healthy controls (92.2% vs. 58.8%; p < 0.01). In the CMA group, molecular genetic testing of GG, GA, and AA genotypes of single nucleotide IL-13 R130Q gene polymorphisms showed significantly higher rates of GA and AA polymorphic locus genotypes compared to healthy controls (43.5% vs. 22.4%, p < 0.05 and 8.7% vs. 0%, p < 0.05, respectively). In future studies, the genotypic and allelic distribution of these polymorphic variants will be determined in children with CMA and healthy children.
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Levels of DNA damage represent the dynamics between damage formation and removal. Therefore, to better interpret human biomonitoring studies with DNA damage endpoints, an individual's ability to recognize and properly remove DNA damage should be characterized. Relatively few studies have included DNA repair as a biomarker and therefore, assembling and analyzing a pooled database of studies with data on base excision repair (BER) was one of the goals of hCOMET (EU-COST CA15132). A group of approximately 1911 individuals, was gathered from 8 laboratories which run population studies with the comet-based in vitro DNA repair assay. BER incision activity data were normalized and subsequently correlated with various host factors. BER was found to be significantly higher in women. Although it is generally accepted that age is inversely related to DNA repair, no overall effect of age was found, but sex differences were most pronounced in the oldest quartile (>61 years). No effect of smoking or occupational exposures was found. A body mass index (BMI) above 25 kg/m2 was related to higher levels of BER. However, when BMI exceeded 35 kg/m2, repair incision activity was significantly lower. Finally, higher BER incision activity was related to lower levels of DNA damage detected by the comet assay in combination with formamidopyrimidine DNA glycosylase (Fpg), which is in line with the fact that oxidatively damaged DNA is repaired by BER. These data indicate that BER plays a role in modulating the steady-state level of DNA damage that is detected in molecular epidemiological studies and should therefore be considered as a parallel endpoint in future studies.
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Dano ao DNA , Reparo do DNA , Ensaio Cometa , Reparo do DNA/genética , DNA-Formamidopirimidina Glicosilase , Estudos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The comet assay or single cell gel electrophoresis, is the most common method used to measure strand breaks and a variety of other DNA lesions in human populations. To estimate the risk of overall mortality, mortality by cause, and cancer incidence associated to DNA damage, a cohort of 2,403 healthy individuals (25,978 person-years) screened in 16 laboratories using the comet assay between 1996 and 2016 was followed-up. Kaplan-Meier analysis indicated a worse overall survival in the medium and high tertile of DNA damage (p < 0.001). The effect of DNA damage on survival was modelled according to Cox proportional hazard regression model. The adjusted hazard ratio (HR) was 1.42 (1.06-1.90) for overall mortality, and 1.94 (1.04-3.59) for diseases of the circulatory system in subjects with the highest tertile of DNA damage. The findings of this study provide epidemiological evidence encouraging the implementation of the comet assay in preventive strategies for non-communicable diseases.
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Ácidos Nucleicos Livres/genética , Dano ao DNA/genética , Neoplasias/genética , Ensaio Cometa , Humanos , Estimativa de Kaplan-Meier , Leucócitos/patologia , Neoplasias/mortalidade , Modelos de Riscos ProporcionaisRESUMO
DNA damage and unrepaired or insufficiently repaired DNA double-strand breaks as well as telomere shortening contribute to the formation of structural chromosomal aberrations (CAs). Non-specific CAs have been used in the monitoring of individuals exposed to potential carcinogenic chemicals and radiation. The frequency of CAs in peripheral blood lymphocytes (PBLs) has been associated with cancer risk and the association has also been found in incident cancer patients. CAs include chromosome-type aberrations (CSAs) and chromatid-type aberrations (CTAs) and their sum CAtot. In the present study, we used data from our published genome-wide association studies (GWASs) and extracted the results for 153 DNA repair genes for 607 persons who had occupational exposure to diverse harmful substances/radiation and/or personal exposure to tobacco smoking. The analyses were conducted using linear and logistic regression models to study the association of DNA repair gene polymorphisms with CAs. Considering an arbitrary cutoff level of 5 × 10-3, 14 loci passed the threshold, and included 7 repair pathways for CTA, 4 for CSA, and 3 for CAtot; 10 SNPs were eQTLs influencing the expression of the target repair gene. For the base excision repair pathway, the implicated genes PARP1 and PARP2 encode poly(ADP-ribosyl) transferases with multiple regulatory functions. PARP1 and PARP2 have an important role in maintaining genome stability through diverse mechanisms. Other candidate genes with known roles for CSAs included GTF2H (general transcription factor IIH subunits 4 and 5), Fanconi anemia pathway genes, and PMS2, a mismatch repair gene. The present results suggest pathways with mechanistic rationale for the formation of CAs and emphasize the need to further develop techniques for measuring individual sensitivity to genotoxic exposure.
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Although the dichotomous classification of metabolic syndrome (MS) enables the classification of individuals as MS-free or presenting MS, it is inconvenient for assessing cardiometabolic risk in MS-free individuals. Continuous MS score allows for estimation of cardiometabolic burden even in MS-free subjects. We used the scores to estimate the proportion of MS-free subjects on high cardiometabolic risk. A total of 876 subjects (62% females) of Central European descent, aged 20-81 years, were included. International Diabetes Federation (IDF) criteria were employed to classify MS. Continuous scores were calculated. We used the receiver operating characteristics (ROC) analysis to estimate the cutoff value to determine the proportion of MS-free subjects on increased risk. Using the waist circumference, 38% of males and 23% of females presented MS. ROC area under the curves (90%-98%) showed an acceptable performance of both scores to classify the presence of MS. Up to 18% of MS-free males and up to 10% of females displayed continuous score ≥ the relevant cutoff point. The waist-to-height ratio performed similar results. Both continuous scores were proven credible for assessing cardiometabolic risk in MS-free subjects. Clinically, this is important for earlier intervention. Despite minor differences between waist circumference and waist-to-height ratio, it would be appropriate to objectify it using reference population. Novelty: The first study using Z-MSS/siMSS (population-specific Z-score/continuous score of MS) to estimate cardiometabolic risk in Slovak adults. A proportion of MS-free Slovak adults is on high cardiometabolic risk. Difference between using waist circumference and the waist-to-height ratio does not seem to be major in our cohort.
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Fatores de Risco de Doenças Cardíacas , Síndrome Metabólica/etiologia , Circunferência da Cintura , Razão Cintura-Estatura , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Nonspecific structural chromosomal aberrations (CAs) can be found at around 1% of circulating lymphocytes from healthy individuals but the frequency may be higher after exposure to carcinogenic chemicals or radiation. The frequency of CAs has been measured in occupational monitoring and an increased frequency of CAs has also been associated with cancer risk. Alterations in DNA damage repair and telomere maintenance are thought to contribute to the formation of CAs, which include chromosome type of aberrations and chromatid type of aberrations. In the present study, we used the result of our published genome-wide association studies to extract data on 153 DNA repair genes from 866 nonsmoking persons who had no known occupational exposure to genotoxic substances. Considering an arbitrary cut-off level of P< 5 × 10-3, single nucleotide polymorphisms (SNPs) tagging 22 DNA repair genes were significantly associated with CAs and they remained significant at P < 0.05 when adjustment for multiple comparisons was done by the Binomial Sequential Goodness of Fit test. Nucleotide excision repair pathway genes showed most associations with 6 genes. Among the associated genes were several in which mutations manifest CA phenotype, including Fanconi anemia, WRN, BLM and genes that are important in maintaining genome stability, as well as PARP2 and mismatch repair genes. RPA2 and RPA3 may participate in telomere maintenance through the synthesis of the C strand of telomeres. Errors in NHEJ1 function may lead to translocations. The present results show associations with some genes with known CA phenotype and suggest other pathways with mechanistic rationale for the formation of CAs in healthy nonsmoking population.
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Aberrações Cromossômicas , Reparo do DNA/genética , não Fumantes , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Simulação por Computador , República Tcheca , Reparo de Erro de Pareamento de DNA/genética , Enzimas Reparadoras do DNA/genética , Proteínas de Ligação a DNA/genética , Feminino , Estudo de Associação Genômica Ampla , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Poli(ADP-Ribose) Polimerases/genética , RecQ Helicases/genética , Proteína de Replicação A/genética , Eslováquia , Helicase da Síndrome de Werner/genética , População Branca/genética , Adulto JovemRESUMO
Genomic instability is a characteristic of a majority of human malignancies. Chromosomal instability is a common form of genomic instability that can be caused by defects in mitotic checkpoint genes. Chromosomal aberrations in peripheral blood are also indicative of genotoxic exposure and potential cancer risk. We evaluated associations between inherited genetic variants in 33 mitotic checkpoint genes and the frequency of chromosomal aberrations (CAs) in the presence and absence of environmental genotoxic exposure. Associations with both chromosome and chromatid type of aberrations were evaluated in two cohorts of healthy individuals, namely an exposed and a reference group consisting of 607 and 866 individuals, respectively. Binary logistic and linear regression analyses were performed for the association studies. Bonferroni-corrected significant p-value was 5 × 10-4 for 99 tests based on the number of analyzed genes and phenotypes. In the reference group the most prominent associations were found with variants in CCNB1, a master regulator of mitosis, and in genes involved in kinetochore function, including CENPH and TEX14, whereas in the exposed group the main association was found with variants in TTK, also an important gene in kinetochore function. How the identified variants may affect the fidelity of mitotic checkpoint remains to be investigated, however, the present study suggests that genetic variation may partly explain interindividual variation in the formation of CAs.
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Aberrações Cromossômicas , Cinetocoros/metabolismo , Pontos de Checagem da Fase M do Ciclo Celular/genética , Polimorfismo de Nucleotídeo Único , Adulto , Células Cultivadas , Proteínas Cromossômicas não Histona/genética , Estudos de Coortes , Ciclina B1/genética , Quinases Ciclina-Dependentes/genética , Feminino , Frequência do Gene , Humanos , Modelos Lineares , Masculino , Razão de Chances , Fatores de Transcrição/genética , Quinase Ativadora de Quinase Dependente de CiclinaRESUMO
OBJECTIVE: Nanomaterials consist of particles smaller than 100 nm - nanoparticles (NPs). Their nano dimensions allow them to penetrate through various membranes and enter into the bloodstream and disseminate into different body organs. Massive expansion of nanotechnologies together with production of new nanoparticles which have not yet been in contact with living organisms may pose a potential health problem. It is therefore necessary to investigate the health impact of NPs after experimental exposure. Comparison of the effect of TiO2 and NPs Fe3O4 in Wistar rats at time intervals 1, 7, 14 and 28 days was performed by studying the cytotoxic effect in the isolated inflammatory cells from bronchoalveolar lavage (BAL). METHODS: Wistar rats were intravenously (i.v.) given a suspension of NPs TiO2 or Fe3O4 (coated by sodium oleate) via the tail vein. After time intervals of 1, 7, 14 and 28 days, we sacrificed the animals under anaesthesia, performed BAL and isolated the cells. The number of animals in the individual groups was 7-8. We examined the differential count of BAL cells (alveolar macrophages - AM, polymorphonuclear leukocytes - PMN, lymphocytes - Ly); viability and phagocytic activity of AM; the proportion of immature and polynuclear cells and enzymes - cathepsin D - CAT D, lactate dehydrogenase - LDH and acid phosphatase - ACP. RESULTS: We found that TiO2 NPs are relatively inert - without induction of inflammatory and cytotoxic response. Exposure to nanoparticles Fe3O4 induced - under the same experimental conditions - in comparison with the control and TiO2 a more extensive inflammatory and cytotoxic response, albeit only at 1, 7 and 14 days after injection. CONCLUSIONS: The results suggest that TiO2 and Fe3O4 nanoparticles used in our study were transferred from the bloodstream to the respiratory tract, but this effect was not observed at 28 days after i.v. injection, probably due to their removal from the respiratory tract.
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Óxido Ferroso-Férrico/toxicidade , Nanopartículas Metálicas/toxicidade , Doenças Respiratórias/induzido quimicamente , Titânio/toxicidade , Administração Intravenosa , Animais , Óxido Ferroso-Férrico/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Ratos , Ratos Wistar , Titânio/administração & dosagemRESUMO
Non-specific structural chromosomal aberrations (CAs) observed in peripheral blood lymphocytes of healthy individuals can be either chromosome-type aberrations (CSAs) or chromatid-type aberrations (CTAs) depending on the stage of cell division they are induced in and mechanism of formation. It is important to study the genetic basis of chromosomal instability as it is a marker of genotoxic exposure and a predictor of cancer risk. For that purpose, we conducted two genome-wide association studies (GWASs) on healthy individuals in the presence and absence of apparent genotoxic exposure from the Czech Republic and Slovakia. The pre-GWAS cytogenetic analysis reported the frequencies of CSA, CTA and total CA (CAtot). We performed both linear and binary logistic regression analysis with an arbitrary cut-off point of 2% for CAtot and 1% for CSA and CTA. Using the statistical threshold of 1.0 × 10-5, we identified five loci with in silico predicted functionality in the reference group and four loci in the exposed group, with no overlap between the associated regions. A meta-analysis on the two GWASs identified further four loci with moderate associations in each of the studies. From the reference group mainly loci within genes related to DNA damage response/repair were identified. Other loci identified from both the reference and exposed groups were found to be involved in the segregation of chromosomes and chromatin modification. Some of the discovered regions in each group were implicated in tumourigenesis and autism.
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Aberrações Cromossômicas/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Frequência do Gene , Genética Populacional , Mutagênicos/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Análise Citogenética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
The genotoxicity of TiO2 nanoparticles (NPs) was assessed with the cytokinesis-block micronucleus (CBMN) assay in TK6 lymphoblastoid cells, lymphocytes from human volunteers, and bone marrow erythrocytes from rats exposed in vivo; and with the comet assay (detecting both strand breaks and oxidised purines) in human and rat peripheral blood mononuclear cells (PBMCs). NPs were dispersed using three different methods giving different size distribution and stability. On average, TiO2 NPs caused no increase in micronuclei in TK6 cells, rat bone marrow erythrocytes or human lymphocytes (though lymphocytes from 3 out of 13 human subjects showed significant increases). PBMCs from rats treated in vivo with a single dose of NPs dispersed by a method with low agglomeration showed an increase in strand breaks after 1 day. TiO2 NPs dispersed in a stable, non-agglomerated state induced DNA strand breaks at 75 µg/cm2 after 4 h exposure of human PBMCs and at 15 µg/cm2 and 75 µg/cm2 after 24 h exposure, but no increase in DNA oxidation was seen. Overall, NPs in an agglomerated state did not cause DNA damage. However, at the individual level, significant increases in strand breaks were seen in PBMCs from most of the volunteers. Cells from one volunteer showed positive effects in all conditions and both tests, while cells from another volunteer appeared to be completely resitant to TiO2 NPs. The implication is that some individuals may be more sensitive than others to effects of this nanomaterial. Differences seen in results obtained with the micronucleus and the comet assay may be due to the mechanisms underlying the genotoxic effects of TiO2 NPs and the different endpoints represented by the two assays.
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Ensaio Cometa , Dano ao DNA , Testes para Micronúcleos , Nanopartículas/toxicidade , Titânio/toxicidade , Adulto , Animais , Linhagem Celular , Quebras de DNA , Eritrócitos/efeitos dos fármacos , Feminino , Humanos , Leucócitos Mononucleares/química , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/ultraestrutura , Linfócitos/química , Linfócitos/efeitos dos fármacos , Linfócitos/ultraestrutura , Masculino , Pessoa de Meia-Idade , Ratos , Ratos WistarRESUMO
Chromosomal aberrations (CAs) in human peripheral blood lymphocytes (PBL) measured with the conventional cytogenetic assay have been used for human biomonitoring of genotoxic exposure for decades. CA frequency in peripheral blood is a marker of cancer susceptibility. Previous studies have shown associations between genetic variants in metabolic pathway, DNA repair and major mitotic checkpoint genes and CAs. We conducted a genome-wide association study on 576 individuals from the Czech Republic and Slovakia followed by a replication in two different sample sets of 482 (replication 1) and 1288 (replication 2) samples. To have a broad look at the genetic susceptibility associated with CA frequency, the sample sets composed of individuals either differentially exposed to smoking, occupational/environmental hazards, or they were untreated cancer patients. Phenotypes were divided into chromosome- and chromatid-type aberrations (CSAs and CTAs, respectively) and total chromosomal aberrations (CAtot). The arbitrary cutoff point between individuals with high and low CA frequency was 2% for CAtot and 1% for CSA and CTA. The data were analyzed using age, sex, occupation/cancer and smoking history as covariates. Altogether 11 loci reached the P-value of 10-5 in the GWAS. Replication 1 supported the association of rs1383997 (8q13.3) and rs2824215 (21q21.1) in CAtot and rs983889 (5p15.1) in CTA analysis. These loci were found to be associated with genes involved in mitosis, response to environmental and chemical factors and genes involved in syndromes linked to chromosomal abnormalities. Identification of new genetic variants for the frequency of CAs offers prediction tools for cancer risk in future. Environ. Mol. Mutagen. 60:17-28, 2019. © 2018 Wiley Periodicals, Inc.
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Aberrações Cromossômicas/estatística & dados numéricos , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Neoplasias/genética , Adulto , Transtorno Autístico/genética , Análise Citogenética , República Tcheca , Dano ao DNA/genética , Reparo do DNA/genética , Síndrome de Down/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , EslováquiaRESUMO
PURPOSE: To determine the DNA protective effects of a standard coffee beverage in comparison to water consumption. METHODS: The single-blind, randomised controlled study with parallel design included healthy women (n = 50) and men (n = 50) recruited from the general Central European population. The subjects were randomised in a coffee and a control group, with stratification for sex and body mass index. The study comprised two periods of 4 weeks: a preconditioning period, with daily consumption of at least 500 ml water but no coffee, nor tea, nor any other caffeine-containing product. During the subsequent intervention period the coffee group consumed 500 ml of freshly brewed dark roast coffee blend per day, the control group consumed water instead. On the last day of each period, blood was drawn and analysed by comet assay (single-cell gel electrophoresis) to assess the level of DNA damage (strand breakage). RESULTS: At the end of the intervention period the mean level of DNA strand breaks in the coffee group has decreased in comparison to the control group [difference in means 0.23% TI (tail intensity), p = 0.028]. The mean change from baseline (delta value) was - 23% in the coffee group (p = 0.0012). Effects of coffee intake were similar for men and women. During intervention, neither group showed any significant change in body weight or calorie intake. CONCLUSIONS: Our results indicate that regular consumption of a dark roast coffee blend has a beneficial protective effect on human DNA integrity in both, men and women.
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Café , Dano ao DNA/efeitos dos fármacos , Adulto , Culinária , Europa (Continente) , Feminino , Temperatura Alta , Humanos , Masculino , Método Simples-CegoRESUMO
OBJECTIVE: Nanomaterials are materials consisting of particles having one or more dimensions smaller than 100 nm. Nanoparticles (NP) have different properties and effects in comparison with the same particle materials of larger size. They can penetrate through various membranes and get from the bloodstream to other organs in the body. Therefore, in our experiment we have dealt with the impact of nanoparticles TiO2 instilled intravenously (i.v.) (to a tail vein of an animal) on the selected parameters of bronchoalveolar lavage (BAL). The aim of our study was to determine whether TiO2 nanoparticles do pass through the vascular system to the respiratory tract, and if so, how they affect the selected inflammatory and cytotoxic parameters of bronchoalveolar lavage. METHODS: Wistar rats were intravenously given a suspension of TiO2 nanoparticles in saline solution. This suspension contained 10% volume of rat serum in dose: 1.0% from LD50 = 0.592 mg/kg of animal body weight. After the time intervals 1, 7, 14 and 28 days, the animals were sacrificed under anaesthesia; bronchoalveolar lavage was performed and the BAL cells were isolated. We have examined these markers: differential count of BAL cells - alveolar macrophages (AM), polymorphonuclear leukocytes (PMNL), lymphocytes (Ly); viability and phagocytic activity of AM; proportion of immature cells and cathepsin D enzyme levels. RESULTS: Regarding the respiratory toxicity of TiO2 nanoparticles we have found that TiO2 nanoparticles are relatively inert. BAL examined parameters (except the immature form of AM) were not significantly changed after 28 days of instillation compared to the control group. We found that the TiO2 nanoparticles used in our study were transferred from the bloodstream to the respiratory tract, but in a 28-day phase after i.v. instillation have been largely eliminated by the defence mechanism from the respiratory tract. CONCLUSIONS: We suggest low biopersistence and relatively rapid elimination of TiO2 nanoparticles from the lung under used experimental conditions.
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Líquido da Lavagem Broncoalveolar/química , Nanopartículas Metálicas/toxicidade , Titânio/toxicidade , Administração Intravenosa , Animais , Nanopartículas Metálicas/administração & dosagem , Tamanho da Partícula , Ratos , Ratos Wistar , Titânio/administração & dosagemRESUMO
OBJECTIVES: Central obesity represents an increased risk to develop cardiovascular diseases. Guidelines of international societies suggest estimating central obesity by measuring waist circumference (WC). Robust statistical data in literature provide evidence on the superiority of waist-to-height ratio (WHtR) over WC and body mass index (BMI) for detecting cardiometabolic risk in both genders. Based on measurements of weight, height and waist circumference we compared the prevalence of central obesity using both the above mentioned criteria in the apparently healthy Slovak adults, and compared the prevalence of central obesity to that of general obesity (BMI). METHODS: Data collected from 5,184 individuals (45% males) aged ≥18 years in four cross-sectional studies carried out between the years 2009-2012 were subjected to secondary analysis. RESULTS: Waist circumference underestimated central obesity in males and overestimated in females: 37.3% of males and 41.8% of females presented central obesity according to WC, 54.2% males and 34.9% females according to WHtR. 17.3% of males centrally obese according to WC present WHtR < 0.5; while 7.8% of females centrally obese according to their WHtR do not display increased WC. The frequency of central obesity increased with age. According to BMI, the prevalence of overweight was 39% in males and 22% in females; that of obesity was 17% and 15%, respectively. CONCLUSION: The prevalence of central obesity estimated using WC vs. WHtR differs significantly in Slovak adults. WHtR is considered superior for detection of the risk of future development of cardiovascular afflictions. Thus, further studies addressing the gender-associated discordance of central obesity measures are required to determine whether our results are consistent across geographical regions and ethnic groups.
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Obesidade/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antropometria , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/epidemiologia , Prevalência , Fatores Sexuais , Eslováquia/epidemiologia , Circunferência da Cintura , Razão Cintura-EstaturaRESUMO
AIM: To determine the levels of circulating soluble receptor for advanced glycation end products (sRAGE), as a biomarker of risk of metabolic syndrome and cardiovascular disease development in centrally obese (CO) women considered metabolically healthy (COH) in comparison with those metabolically unhealthy (COU). METHODS: 47 lean healthy, 17 COH (presenting waist-to-height ratio ≥0.5 but not elevated blood pressure, atherogenic lipid profile, and insulin resistance), and 50 COU (CO presenting ≥2 risk factors) women aged 40-45 years were included. Anthropometric characteristics, blood chemistry and hematology data, adipokines, markers of inflammation, sRAGE, soluble vascular adhesion protein-1 (sVAP-1), and the activity of semicarbazide sensitive amine oxidase (SSAO) were determined. RESULTS: Central obesity associated with low sRAGE levels (lean healthy: 1503±633 pg/mL; COH: 1103±339 pg/mL, P<0.05; COU: 1106±367 ng/mL, P<0.0.1), hyperleptinemia, and elevated markers of inflammation irrespective of the presence or absence of cardiometabolic risk factors. COU women presented high adiponectin levels. SVAP-1 concentrations and the activity of SSAO were similar in all 3 groups. CONCLUSION: COH women present abnormalities in non-standard markers of cardiometabolic risk (sRAGE, leptin, high sensitive C-reactive protein), supporting the view that there is no healthy pattern of obesity. The clinical impact of our findings for future prognosis of metabolically healthy obese subjects remains to be elucidated in longitudinal studies.