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Introduction: Obesity is a pathological state that involves the dysregulation of different metabolic pathways and adipose tissue cells, constituting a risk factor for the development of other diseases. Bariatric surgery is the most effective treatment. The study of the behavior of pollutants in situations of extreme weight loss can provide biomonitoring information and tools to manage diseases of environmental etiology. Aim: To determine the prevalence of serum persistent and non-persistent pollutants in obese patients subjected to bariatric surgery and analyze the impact of sociodemographic variables on these changes. Methods: GC-MS/MS and UHPLC-MS/MS were utilized to determine the detection rates and concentrations of 353 compounds, including persistent organic pollutants (POPs), pesticides, pharmaceuticals, and rodenticide, in serum samples of 59 obese patients before and after undergoing bariatric surgery. Results: Detection rates of p,p'-DDE, HCB, ß-HCH, naphthalene, phenanthrene and PCB congeners 138, 153 and 180 significantly increased due to surgery-induced weight loss. Serum levels of p,p'-DDE, PCB-138, PCB-153 and PCB-180 also increased after surgery. Correlations between naphthalene levels, weight loss, variation of total lipids and time after surgery were found. Additionally, correlations were observed between concentrations of PCB-138 and weight loss, and between phenanthrene levels and reduction of total lipids. No statistically significant differences were observed for other groups of contaminants, pharmaceuticals and other chemicals included in the quantification methods. Conclusions: Increment of POPs was observed after bariatric surgery. Serum concentrations of POPs after surgery were influenced by adiposity-related variables. Although biomonitoring studies show a decreasing tendency of exposure, rapid weight loss leads to an increase of circulating POPs. Further research on the interplay between adipose tissue, POPs and peripheral organs is required.
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Cirurgia Bariátrica , Obesidade Mórbida , Humanos , Feminino , Masculino , Obesidade Mórbida/cirurgia , Obesidade Mórbida/sangue , Adulto , Estudos Longitudinais , Pessoa de Meia-Idade , Poluentes Orgânicos Persistentes/sangue , Carga Corporal (Radioterapia) , Poluentes Ambientais/sangue , Redução de Peso , Estudos de Coortes , Espectrometria de Massas em TandemRESUMO
Animals and humans are exposed to various residues that can have a detrimental impact on health, including carcinogenic potential, endocrine disruption, or fatal toxicity. The toxic burden can be evaluated in several biological samples, with serum being one of the preferred and most convenient options. In this study, we have applied and validated a method for detecting several hundred toxins in serum samples. This technique involved a single-step QuEChERS (quick, easy, cheap, effective, rugged, and safe) extraction followed by analysis using gas and liquid chromatography coupled with mass spectrometry. With this methodology, we could detect and quantify up to 353 compounds, including persistent organic pollutants (POPs), pesticides, pharmaceuticals, and rodenticides, using just 250 µL of serum. Among them, 92% could be measured at concentrations below 1.25 ng/mL, making it ideal for biomonitoring. We applied this method to samples collected from camels (n = 40) and humans (n = 25). We detected naproxen, ketoprofen, paracetamol, levamisole, and some POPs in these samples. This study validated the ability to simultaneously detect a broad range of compounds in small volumes of serum.
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Several studies have examined the association between prenatal exposure to organophosphate and pyrethroid pesticides and their impact on foetal growth and newborn anthropometry; however, the available evidence is limited and inconclusive. This study examined whether prenatal organophosphate and pyrethroid pesticide exposure was associated with anthropometric measures at birth (weight, length, head circumference), ponderal index, gestational age, and prematurity in 537 mother-child pairs. These were randomly selected from the 800 pairs participating in the prospective birth cohort GENEIDA (Genetics, early life environmental exposures and infant development in Andalusia). Six non-specific organophosphate metabolites (dialkylphosphates, DAPs), one metabolite relatively specific to chlorpyrifos (3,5,6-trichloro-2-pyridinol, TCPy) and a common metabolite to several pyrethroids (3-phenoxybenzoic acid, 3-PBA) were measured in maternal urine from the 1st and 3rd pregnancy trimesters. Information on anthropometric measures at birth, gestational age and prematurity was retrieved from medical records. The sum on a molar basis of DAPs with methyl (Æ©DMs) and ethyl (Æ©DEs) moieties and the sum of the 6 DAPs metabolites (Æ©DAPs) was calculated for both trimesters of pregnancy. High urinary levels of dimethyl phosphate (DMP) during the 3rd trimester were associated with a decrease in birth weight (ß = -0.24; 95% CI: 0.41; -0.06) and birth length (ß = -0.20; 95% CI: 0.41; 0.02). Likewise, ΣDMs during 3rd trimester were near-significantly associated with decreased birth weight (ß = -0.18; 95% CI: 0.37; 0.01). In turn, increased urinary TCPy during 1st trimester was associated with a decreased head circumference (ß = -0.31; 95% CI: 0.57; -0.06). Finally, an increase in 3-PBA in the 1st trimester was associated with a decreased gestational age (ß = -0.36 95% CI: 0.65-0.08), whereas increased 3-PBA at 1st and 3rd trimester was associated with prematurity. These results indicate that prenatal exposure to organophosphate and pyrethroid insecticides could affect normal foetal growth, shorten gestational age and alter anthropometric measures at birth.
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Clorpirifos , Praguicidas , Efeitos Tardios da Exposição Pré-Natal , Piretrinas , Recém-Nascido , Lactente , Feminino , Humanos , Gravidez , Praguicidas/toxicidade , Praguicidas/urina , Piretrinas/toxicidade , Piretrinas/urina , Organofosfatos/toxicidade , Organofosfatos/urina , Peso ao Nascer , Estudos Prospectivos , Idade Gestacional , Exposição Materna , Clorpirifos/urina , Exposição AmbientalRESUMO
Medical psychotropics are widely used and prescribed in developed countries. These medications may have an impairing effect on mood or perception and may induce harmful behaviors. Nevertheless, in Europe, studies on their importance from a medico-legal perspective are scarce. To fill this gap, we evaluate the determinants of these drugs in a retrospective study based on data obtained from forensic autopsies. Toxicological analyses were performed on 394 blood samples from compulsory autopsies at the Institute of Legal Medicine of Las Palmas. Of the samples, 41% (159) were positive for at least one psychotropic, with benzodiazepines being the most frequently detected (24.1%), followed by opiates and antidepressants. Benzodiazepines, opiates, and antidepressants were detected more frequently in men who suffered a violent death. More than 30% of the positive samples showed two or more drugs, suggesting a prevalence of polypharmacy among forensic autopsy subjects, with the most frequently combination found being benzodiazepines plus opiates (28.3% of positive samples). A combination of opiates plus antidepressants was also found in subjects involved in violent deaths. Our results suggest that more than 40% of the adult European population involved in medico-legal issues may be under the influence of legal psychotropics. The link between violent deaths and the use of medical psychotropics is particularly worrisome and indicates that these drugs should be carefully monitored in developed countries, in all forensic autopsies, in a similar way to illegal psychotropics.
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The screening of hundreds of substances belonging to multiple chemical classes in liver is required in areas such as food safety or biomonitoring. We adapted a previous QuEChERS-based method in blood to the liver matrix and applied to these fields of study. The validation of the method allowed the inclusion of 351 contaminants, 80% with a LOQ < 2 ng/g. In the analysis of 42 consumer liver samples, we detected trace levels of 29 different contaminants. The most frequent and concentrated was 4,4'-DDE. POPs accounted for 66% of the compounds detected. In no case was the MRL reached for any of the contaminants detected. We also applied the method to 151 livers of wild birds to perform a biomonitoring pilot study in the Canary Islands. We detected 52 contaminants in 15 bird species. These were also mostly POPs, although high frequencies and concentrations of anticoagulant rodenticides (AR) and some other agricultural pesticides also stand out. POPs and AR contamination levels were significantly higher in terrestrial birds, raptors and particularly in nocturnal birds. Pesticide contamination levels were also higher in terrestrial birds, as well as in non-raptors and diurnal birds. The validated method is simple, robust, and sensitive and performs well in a variety of practical scenarios, where it can be carried out relatively quickly and inexpensively.
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Inorganic elements have been associated with brain tumours for long. The blood concentration of 47 elements was assessed by ICP-MS in 26 brain tumour patients and 21 healthy subjects from Bucharest (Romania). All 47 elements were detected in the brain tumour tissue, and 22 were detected in > 80% of samples; this implies that these elements can cross the blood-brain barrier. Median blood levels of cadmium, lead, and nickel were higher than the reference values (1.14, 53.3, and 2.53 ng/mL). Gadolinium and tantalum showed significantly higher concentrations among cases. We observed considerable differences and different profiles of the presence of inorganic elements between the tumour and non-tumour brain tissue and between tissue from the primary tumour and tissue from brain metastasis. Our data suggest that similar to heavy metals, other elements - commonly used in high tech devices and rare earth elements - can also influence brain tumour.
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Neoplasias Encefálicas/metabolismo , Encéfalo/metabolismo , Metais Pesados/análise , Metais Terras Raras/análise , Adulto , Idoso , Monitoramento Biológico , Neoplasias Encefálicas/patologia , Estudos de Casos e Controles , Feminino , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Masculino , Meningioma/metabolismo , Meningioma/patologia , Metais Pesados/sangue , Metais Pesados/metabolismo , Metais Terras Raras/sangue , Metais Terras Raras/metabolismo , Pessoa de Meia-Idade , RomêniaRESUMO
Persistent organic pollutants (POPs) have been banned over the last decades for being damaged to the environment and to the health of humans and animals. However, due to their lipophilic nature and resistance to degradation, they are frequently detected in biological samples. Its presence has been associated with the increased risk of suffering from different diseases in human series, being newborns and children especially sensitive. The present data reports umbilical cord blood levels of twenty organochlorine pesticides (aldrin, dieldrin, endrin, o,p'-DDD, p,p'-DDD, o,p'-DDE, p,p'-DDE, o,p'-DDT, p,p'-DDT, endosulfan alfa, endosulfan beta, endosulfan sulphate, heptachlor, HCB, αHCH, ßHCH, δHCH, lindane, methoxychlor and mirex), eighteen polychlorinated biphenyls (congeners 28, 52, 77, 81, 101, 105, 114, 118, 123, 126, 138, 153, 156, 157, 167, 169, 180 and 189), eight bromodiphenyl ethers (congeners 28, 47, 85, 99, 100, 153, 154 and 183), and sixteen polycyclic aromatic hydrocarbons (acenaphthalene, acenaphthene, anthracene, benzo(a)anthracene, benzo(a)pyrene, benzo(b)fluoranthene, benzo(g,h,i)perylene, benzo(k)fluoranthene, chrysene, dibenzo(a,h)anthracene, fluoranthene, fluorine, indene(1,2,3-cd)pyrene, naphthalene, phenanthrene and pyrene). A total of 447 samples, representing 86.6% of the total births during the recruited period (March 1, 2015, to April 30, 2016), were available for POP analyses. POPs were determined in a Gas Chromatography (GC) system equipped with an automated sampler (Models 7890B and 7693; Agilent Technologies, Palo Alto, CA, USA) for gas chromatographic separations. The detection of the analytes was performed using a Triple Quad 7010 mass spectrometer (Agilent Technologies). All of the measurements were performed as triplicate measurements, and the means were used for the calculations. Data are reported in ng/mL. The present data also includes birth parameters, including weight, length, cranial perimeter, Apgar score and congenital malformations, and data referred to mothers (harmful habits, chronic diseases, and anthropometric/demographic characteristics).
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It is known that cigarette smoking is correlated with medical associated inquires. New electronic cigarettes are intensively advertised as an alternative to conventional smoking, but only a few studies demonstrate their harmful potential. A cross-sectional study was designed using 150 subjects from Brasov (Romania), divided into three groups: non-smokers (NS = 58), conventional cigarettes smokers (CS = 58) and electronic cigarettes users (ECS = 34). The aim of this study was to determine levels of some plasma lipophilic and hematological components, and the total antioxidant status that could be associated with the smoking status of the subjects. Serum low density lipoproteins (LDL) cholesterol increased significantly for ECS participants versus NS group (18.9% difference) (p < 0.05). Also, the CS group is characterized by an increase of serum LDL cholesterol (7.9% difference vs. NS), but with no significant statistical difference. The variation of median values of serum very low density lipoproteins (VLDL) was in order NS < ECS < CS, with statistical difference between NS and CS groups (34.6% difference; p = 0.023). When comparing the antioxidant status of the three groups, significant differences (p < 0.05) were obtained between NS vs. CS and NS vs. ECS. Similar behavior was identified for CS and ECS. Statistically significant changes (p < 0.0001) for both vitamin A and vitamin E were identified in the blood of NS vs. CS and NS vs. ECS, and also when comparing vitamin A in the blood of the CS group versus the ECS group (p < 0.05). When all groups were compared, the difference in the white blood cell (WBC) was (p = 0.008). A slight increase in the red blood cell (RBC) count was observed, but with no statistical difference between groups. These results indicated that conventional cigarette and e-cigarette usage promotes the production of excess reactive oxygen species, involving different pathways, different antioxidants and bioactive molecules.
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Environmental pollution due to various elements is increasing all across the planet owing to their use in industrial processes. The tobacco plants and the vegetables used in the manufacturing of smoking paper may accumulate these elements from the environment. Thus, tobacco and smoking paper may be relevant contributors among the content of elements in cigarettes, including some emerging pollutants such as rare earth elements (REEs). Thirty-two elements related to hi-tech industrial processes were analyzed in tobacco, rolling paper, and filters (nâ¯=â¯257 samples) by ICP-MS. A variety of industrial brands and "roll-your-own" cigarette papers were considered. The potential maximum daily exposure to these elements by a hypothetical heavy smoker was calculated for each type of cigarette. We found significant differences in the levels of most elements, both in the tobacco and in the paper. Black tobacco cigarettes contained the maximum levels. We found that the paper used in roll-your-own cigarettes may significantly modify their concentration of elements. Fast-burning, bleached, and flavored papers also contribute to higher levels of these pollutants. Thus, the differences in theoretical exposure depending on the type of cigarette consumed-either branded or hand-rolled-may be very striking, of up to 35-40 times. In addition to the number of cigarettes consumed per day, it is necessary to consider the type of cigarette consumed to assess the risk of exposure to toxic elements. Tobacco paper is a prominent source of exposure to toxic elements. Cigarette smoke is another source of exposure to emerging contaminants such as REE.
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Fumar Cigarros , Exposição Ambiental/análise , Substâncias Perigosas/toxicidade , Produtos do Tabaco , Fumaça , Fumar , NicotianaRESUMO
Traditionally, a major part of aquaculture technology requires fish oil (FO) and fish meal (FM) to produce the aquafeed for farmed species. FO is the main source of persistent organic pollutants (POPs) in fish feed. In recent years, the use of vegetable-origin ingredients in fish feeds has been increasingly studied as an alternative to reduce the levels of these lipophilic pollutants in farmed species. The aim of this study was to evaluate the effect of the use of dietary vegetable oils in the farming of European sea bass (Dicentrarchus labrax) on the contents in persistent - polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) - and semi persistent pollutants - polycyclic aromatic hydrocarbons (PAHs) and polybrominated diphenyl ethers (BDEs) - of their edible parts. A total of 60 seabass muscle pools were obtained from fish farmed employing six experimental diets, which contained different percentages of FO (6 vs. 3%) and FM (20%, 10% and 5%). We did not observe differences in the contamination level of seabass muscle in relation to the percentage of FM in their diet. However, the fish farmed using feed which had lower levels of FO (3%) showed significantly lower muscle levels of ΣPCBs and carcinogenic PAHs (Σc-PAHs), with a reduction of 25.6% and 95.11% (respectively), as compared with those fished raised with feed with higher levels of FO (6%). Also much lower levels were found in OCPs such as sum of DDTs (30.88% of reduction), sum of chlordanes (42.85% of reduction), and sum of BDEs (48.16% of reduction) in those seabass fed with a lower percentage of FO. The results of this study indicate that the use of alternative feed ingredients that allow the employment of low percentage of FO in feeds help to reduce the load of several toxic pollutants in the fillets of European seabass.
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Ração Animal/análise , Aquicultura/métodos , Contaminação de Alimentos/prevenção & controle , Alimentos Marinhos/análise , Poluentes Químicos da Água/análise , Animais , Bass , Dieta/métodos , Óleos de Peixe , Peixes/metabolismo , Contaminação de Alimentos/análise , Contaminação de Alimentos/estatística & dados numéricos , Bifenilos Policlorados/análise , Alimentos Marinhos/estatística & dados numéricosRESUMO
Smoking is considered an important source for inorganic elements, most of them toxic for human health. During the last years, there has been a significant increase in the use of e-cigarettes, although the role of them as source of inorganic elements has not been well established. A cross-sectional study including a total of 150 subjects from Brasov (Romania), divided into three groups (non-smokers, cigarette smokers and electronic cigarettes smokers) were recruited to disclose the role of smoking on the human exposure to inorganic elements. Concentration of 42 elements, including trace elements, elements in the ATSDR's priority pollutant list and rare earth elements (REE) were measured by ICP-MS in the blood serum of participants. Cigarette smokers showed the highest levels of copper, molybdenum, zinc, antimony, and strontium. Electronic cigarette (e-cigarette) users presented the highest concentrations of selenium, silver, and vanadium. Beryllium, europium and lanthanides were detected more frequently among e-cigarette users (20.6%, 23.5%, and 14.7%) than in cigarette smokers (1.7%, 19.0%, and 12.1%, respectively); and the number of detected REE was also higher among e-cigarette users (11.8% of them showed more than 10 different elements). Serum levels of cerium and erbium increased as the duration of the use of e-cigarettes was longer. We have found that smoking is mainly a source of heavy metals while the use of e-cigarettes is a potential source of REE. However, these elements were detected at low concentrations.
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Carga Corporal (Radioterapia) , Sistemas Eletrônicos de Liberação de Nicotina , Metais Pesados/sangue , Metais Terras Raras/sangue , não Fumantes , Fumantes , Estudos Transversais , Humanos , Romênia , Oligoelementos/sangueRESUMO
Women all over the world are exposed to an unavoidable contamination by organochlorine pesticides and other chemical pollutants. Many of them are considered as xenoestrogens and have been associated with the development and progression of breast cancer. We have demonstrated that the most prevalent pesticide mixtures found in healthy women and in women diagnosed with breast cancer modulates the gene expression in human epithelial mammary cells. Statins are well-known cholesterol-depleting agents acting as inhibitors of cholesterol synthesis. Since the early 1990s, it has been known that statins could be successfully used in cancer therapy, including breast cancer, but the exact mechanism behind anti-tumor activity of the statins remains unclear. In the present study we evaluated the effect of simvastatin in the gene expression pattern induced by realistic organochlorine mixtures found in breast cancer patients. The gene expression of 94 genes related with the cell signaling pathways were assessed. Our results indicate that simvastatin exerts a global down regulating effect on successfully determined genes (78.7%), thus attenuating the effects induced by organochlorine mixtures on the gene profile of human mammary epithelial cells. This effect was more evident on genes whose function is the ATP-binding process (that also were particularly up-regulated by pesticide mixtures). We also found that MERTK (a proto-oncogene which is overexpressed in several malignancies) and PDGFRB (a member of the platelet-derived growth factor family whose expression is high in breast-cancer cells that have become resistant to endocrine therapy) were among the genes with a higher differential regulation by simvastatin. Since resistance to treatment with tyrosine kinase inhibitors is closely related to MERKT, our findings would enhance the possible utility of statins in breast cancer treatment, i.e. improving therapeutic results combining statins with tyrosine Kinase inhibitors.
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Disruptores Endócrinos/toxicidade , Células Epiteliais/efeitos dos fármacos , Hidrocarbonetos Clorados/toxicidade , Glândulas Mamárias Humanas/efeitos dos fármacos , Praguicidas/toxicidade , Sinvastatina/farmacologia , Linhagem Celular , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Glândulas Mamárias Humanas/citologia , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Proto-Oncogene Mas , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismoRESUMO
"Gofio" is a type of flour made from toasted grain, which is part of the staple food in the Canary Islands, Spain, in which the occurrence of Aflatoxins B1, B2, G1 and G2 (AFB1, AFB2, AFG1, AFG2), Fumonisins B1 and B2 (FB1 and FB2) Ochratoxin A (OTA), Deoxynivalenol (DNV) and Zearalenone (ZEA) was evaluated. 83% of the samples were contaminated with at least one mycotoxin and 69.2% of the analyzed samples showed co-occurrence of mycotoxins (range 2 to 8). All the concentrations were well below the established limits (maximum values of AFs=0.42 µg/kg; FBs=178.3 µg/kg; OTA=0.3 µg/kg; DON=92.5 µg/kg; and ZEA=9.9 µg/kg). The daily dietary exposure to total AFs was estimated to be 7.1% of the TDI. This value was almost double in children, and considering the upper-bound approach could reach 35% of the TDI. For the rest of mycotoxins, the consumers would be exposed to less than 2% of their TDIs. The risk characterization indicates that there is a potential risk in developing aflatoxin induced liver cancer due to gofio consumption in the subpopulation which is simultaneously exposed to other hepatocarcinogens, such as the hepatitis B virus.
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Aflatoxinas/efeitos adversos , Carcinoma Hepatocelular/etiologia , Grão Comestível/química , Exposição Ambiental/efeitos adversos , Neoplasias Hepáticas/etiologia , Micotoxinas/efeitos adversos , Adolescente , Adulto , Carcinoma Hepatocelular/patologia , Criança , Hepatite B/virologia , Vírus da Hepatite B/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/patologia , Venenos/efeitos adversos , EspanhaRESUMO
Organochlorine pesticides (OCs) have been associated with breast cancer development and progression, but the mechanisms underlying this phenomenon are not well known. In this work, we evaluated the effects exerted on normal human mammary epithelial cells (HMEC) by the OC mixtures most frequently detected in healthy women (H-mixture) and in women diagnosed with breast cancer (BC-mixture), as identified in a previous case-control study developed in Spain. Cytotoxicity and gene expression profile of human kinases (n=68) and non-kinases (n=26) were tested at concentrations similar to those described in the serum of those cases and controls. Although both mixtures caused a down-regulation of genes involved in the ATP binding process, our results clearly indicate that both mixtures may exert a very different effect on the gene expression profile of HMEC. Thus, while BC-mixture up-regulated the expression of oncogenes associated to breast cancer (GFRA1 and BHLHB8), the H-mixture down-regulated the expression of tumor suppressor genes (EPHA4 and EPHB2). Our results indicate that the composition of the OC mixture could play a role in the initiation processes of breast cancer. In addition, the present results suggest that subtle changes in the composition and levels of pollutants involved in environmentally relevant mixtures might induce very different biological effects, which explain, at least partially, why some mixtures seem to be more carcinogenic than others. Nonetheless, our findings confirm that environmentally relevant pollutants may modulate the expression of genes closely related to carcinogenic processes in the breast, reinforcing the role exerted by environment in the regulation of genes involved in breast carcinogenesis.
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Neoplasias da Mama/induzido quimicamente , Mama/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Hidrocarbonetos Clorados/toxicidade , Mama/metabolismo , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Oncogenes , Proteínas Quinases/genéticaRESUMO
Polychlorinated biphenyls (PCBs) are toxic and persistent chemicals produced between 1930s and 1980s, which accumulate in humans and wildlife. Although a decreasing trend of PCB levels in humans has been described in developed countries, mainly as a consequence of strict regulations and remediation plans, an inverse trend has been recently reported in people from developing countries. We had the opportunity of sampling a series of African immigrants recently arrived to the Spanish archipelago of the Canary Islands, in which high levels of PCBs have been described, and we studied the relationships between their level of contamination and health status. A total of 570 subjects who underwent a complete medical examination and a face-to-face interview were recruited for this study. Hematological and biochemical parameters (blood and urine) were determined in all participants. Serology for the diagnostic of infectious diseases was also performed, and direct identification of parasites was performed in feces, urine or blood samples when appropriate. It is remarkable that up to 26.0% of the population had intestinal parasites, and we found an inverse relationship between PCB levels and parasitism and parasitic diseases: median values of PCBs were lower in parasitized subjects than in subjects without parasites in stool (237.6ng/g fat vs. 154.4ng/g fat for marker PCBs, p=0.015) and median values of dioxin-like PCBs were lower in subjects carrying pathogen parasites than among subjects showing non-pathogen parasites in stool (0.0 ng/g fat vs. 13.1ng/g fat, respectively; p=0.001). Although this inverse association had been described in some vertebrates this is the first study reporting such an association in humans. Furthermore, it has been also recently described that PCBs may disrupt iron metabolism, and we found a direct relationship between serum iron and total PCBs burden (r=0.231, p=0.025), suggesting that PCBs, although at subclinical level, could play a role on iron homeostasis. Although the role of PCBs in parasitism and in the iron metabolism needs future research, our findings may help to understand the adverse health outcomes associated to environmental exposure to PCBs and they might be used in exposed populations as indicators of subtle effects due to environmental insult.
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População Negra , Emigrantes e Imigrantes , Poluentes Ambientais/sangue , Bifenilos Policlorados/sangue , Adolescente , Adulto , Estudos Transversais , Monitoramento Ambiental , Fezes/parasitologia , Feminino , Homeostase , Humanos , Ferro/sangue , Masculino , Doenças Parasitárias/sangue , Doenças Parasitárias/epidemiologia , Espanha/epidemiologia , Adulto JovemAssuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Inibidores de 5-alfa Redutase/uso terapêutico , Etnicidade/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Frequência do Gene/genética , Predisposição Genética para Doença , Humanos , Masculino , Análise de Componente Principal , Neoplasias da Próstata/enzimologiaRESUMO
BACKGROUND: Prostate cancer (PCa) is an androgen-dependent disease. Nonetheless, the role of single nucleotide polymorphisms (SNPs) in genes encoding androgen metabolism remains an unexplored area. PURPOSE: To investigate the role of germline variations in cytochrome P450 17A1 (CYP17A1) and steroid-5α-reductase, α-polypeptides 1 and 2 (SRD5A1 and SRD5A2) genes in PCa. PATIENTS AND METHODS: In total, 494 consecutive Spanish patients diagnosed with nonmetastatic localized PCa were included in this multicenter study and were genotyped for 32 SNPs in SRD5A1, SRD5A2, and CYP17A1 genes using a Biotrove OpenArray NT Cycler. Clinical data were available. Genotypic and allelic frequencies, as well as haplotype analyses, were determined using the web-based environment SNPator. All additional statistical analyses comparing clinical data and SNPs were performed using PASW Statistics 15. RESULTS: The call rate obtained (determined as the percentage of successful determinations) was 97.3% of detection. A total of 2 SNPs in SRD5A1-rs3822430 and rs1691053-were associated with prostate-specific antigen level at diagnosis. Moreover, G carriers for both SNPs were at higher risk of presenting initial prostate-specific antigen levels>20ng/ml (Exp(B) = 2.812, 95% CI: 1.397-5.657, P = 0.004) than those who are AA-AA carriers. Haplotype analyses showed that patients with PCa nonhomozygous for the haplotype GCTTGTAGTA were at an elevated risk of presenting bigger clinical tumor size (Exp(B) = 3.823, 95% CI: 1.280-11.416, P = 0.016), and higher Gleason score (Exp(B) = 2.808, 95% CI: 1.134-6.953, P = 0.026). CONCLUSIONS: SNPs in SRD5A1 seem to affect the clinical characteristics of Spanish patients with PCa.
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3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Testosterona/metabolismo , Progressão da Doença , Frequência do Gene , Técnicas de Genotipagem , Humanos , Masculino , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Espanha , Esteroide 17-alfa-Hidroxilase/genética , População Branca/genéticaRESUMO
BACKGROUND: Besides serum levels of PSA, there is a lack of prostate cancer specific biomarkers. It is need to develop new biological markers associated with the tumor behavior which would be valuable to better individualize treatment. The aim of this study was to elucidate the relationship between single nucleotide polymorphisms (SNPs) in genes involved in DNA repair and prostate cancer progression. METHODS: A total of 494 prostate cancer patients from a Spanish multicenter study were genotyped for 10 SNPs in XRCC1, ERCC2, ERCC1, LIG4, ATM and TP53 genes. The SNP genotyping was made in a Biotrove OpenArray® NT Cycler. Clinical tumor stage, diagnostic PSA serum levels, and Gleason score at diagnosis were obtained for all participants. Genotypic and allelic frequencies were determined using the web-based environment SNPator. RESULTS: SNPs rs11615 (ERCC1) and rs17503908 (ATM) appeared as risk factors for prostate cancer aggressiveness. Patients wild homozygous for these SNPs (AA and TT, respectively) were at higher risk for developing cT2b - cT4 (OR = 2.21 (confidence interval (CI) 95% 1.47 - 3.31), p < 0.001) and Gleason scores ≥ 7 (OR = 2.22 (CI 95% 1.38 - 3.57), p < 0.001), respectively. Moreover, those patients wild homozygous for both SNPs had the greatest risk of presenting D'Amico high-risk tumors (OR = 2.57 (CI 95% 1.28 - 5.16)). CONCLUSIONS: Genetic variants at DNA repair genes are associated with prostate cancer progression, and would be taken into account when assessing the malignancy of prostate cancer.
Assuntos
Reparo do DNA , Progressão da Doença , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Proteínas Mutadas de Ataxia Telangiectasia/genética , Biomarcadores/sangue , Estudos de Coortes , Dano ao DNA/genética , DNA Ligase Dependente de ATP , DNA Ligases/genética , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Frequência do Gene , Genótipo , Humanos , Modelos Logísticos , Masculino , Gradação de Tumores , Prognóstico , Antígeno Prostático Específico/sangue , Fatores de Risco , Espanha , Proteína Supressora de Tumor p53/genética , População Branca/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-X , Proteína Grupo D do Xeroderma Pigmentoso/genéticaRESUMO
Several studies of environmental samples indicate that the levels of many persistent organic pollutants (POPs) are increasing in Africa, but few studies have been conducted in humans. Simultaneously, many African countries are experiencing a rapid economic growth and implementing information and communication technologies (ICT). These changes have generated high amounts of electronic waste (e-waste) that have not been adequately managed. We tested the hypothesis that the current levels of two main classes of POPs in Western and Central African countries are affected by the degree of socioeconomic development. We measured the levels of 36 POPs in the serum of recent immigrants (N=575) who came from 19 Sub-Saharan countries to the Canary Islands (Spain). We performed statistical analyses on their anthropometric and socioeconomic data. High median levels of POPs were found in the overall sample, with differences among the countries. Organochlorine pesticide (OCP) and polychlorinated biphenyl (PCB) levels increased with age. People from low-income countries had significantly higher OCP levels and much lower PCB levels than those from high-income countries. We found a significant association between the implementation of ICT and PCB contamination. Immigrants from the countries with a high volume of imports of second-hand electronic equipment had higher PCB levels. The economic development of Africa and the e-waste generation have directly affected the levels of POPs. The POP legacies of these African populations most likely are due to the inappropriate management of the POPs' residues.
Assuntos
Exposição Ambiental/análise , Poluentes Ambientais/metabolismo , Hidrocarbonetos Clorados/metabolismo , Praguicidas/metabolismo , África , Exposição Ambiental/estatística & dados numéricos , Humanos , Bifenilos Policlorados/metabolismo , Fatores SocioeconômicosRESUMO
The level of contamination with persistent organic pollutants (POPs) and dietary habits and food consumption was extensively studied in the population from the Canary Islands (Spain). Because foodstuffs of animal origin are well known to be prominent contributors to these contaminants, the current study aimed to assess the role of the dietary intake of animal products as a probability factor for increased serum POPs. The intake of animal products (dietary variables) as a determining factor for serum POP levels was investigated using multivariate statistical models. Our results showed that while poultry, rabbit, and cheese consumption increases the probability of having high levels of non-DDT-derivative pesticides, sausage, yogurt, lard, and bacon consumption decreases the probability of having high levels of these pesticides. In addition, poultry, rabbit, eggs, cream, and butter consumption increased the probability of having detectable levels of marker PCB, while dairy desserts decreased the probability of having detectable levels of these PCBs. On the contrary, sausage and meat consumption increased the probability of having detectable levels of dioxin-like PCBs (DL-PCBs). The current results confirm that dietary intake of foodstuffs of animal origin is a relevant risk factor for the accumulation of POPs (and therefore their serum levels). Our study indicates that the analysis of dietary patterns may be useful for identifying those individuals that will probably present a high body burden of POPs. Because POPs can exert deleterious effects on human health, the identification of populations at risk of being highly contaminated is mandatory in order to implement policies that minimize the exposure to these compounds.