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1.
Pan Afr Med J ; 33: 187, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565147

RESUMO

Fumonisin B1 (FB1) is a mycotoxin frequently found in agricultural commodities. The toxin poses a considerable risk for human and animal health. FB1 is among several mycotoxins produced by Fusarium spp. contaminating virtually any cereal and other Poaceae. Their intracellular action includes the promotion of oxidative stress through the generation of reactive oxygen species (ROS) that damage biomolecules such as DNA. These toxic effects were observed in vivo and in vitro. However, the association between esophageal lesions and oxidative stress induced by FB1. Studies in China, Iran and South Africa showed higher exposure to fumonisins in areas with higher risk of esophageal cancer (EC). Exposure to mycotoxins may be inevitable in Mozambique. How mycotoxins, particularly fumonisins from the contaminated food, can be associated with the emergence of EC in Mozambique? Herein, we revise the literature and present some pieces of evidence in order to highlight the burden of mycotoxins and to provide evidence-based considerations for the stakeholders involved in the management of the EC agenda in Mozambique. The information presented herein supports the need to implement novel and/or to revisit the existent detoxification methods to reduce the global burden of mycotoxins and its outcomes in health management.


Assuntos
Carcinógenos Ambientais/toxicidade , Neoplasias Esofágicas/epidemiologia , Fumonisinas/toxicidade , Micotoxinas/toxicidade , Animais , Neoplasias Esofágicas/etiologia , Contaminação de Alimentos/prevenção & controle , Fusarium/metabolismo , Humanos , Moçambique/epidemiologia , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo
2.
Bull Cancer ; 106(11): 975-982, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31607391

RESUMO

While improvements in the environment and living conditions have contributed to a significant increase in human longevity for over a century, the role of environmental factors in the occurrence of cancer has become a public health concern. It is recognized that a number of environmental factors such as environmental quality (air, water, soil), or environmental changes contribute to the occurrence of certain cancers. Despite this awareness, their potential impacts on health raise many scientific questions. The development of new methodological tools for the characterization of exposure, the study of the association between environmental agents and cancer through an exposure-cancer approach and the health impacts associated, have led to changes in scientific paradigms including the concept of exposome. This concept, at the heart of health and environmental issues, takes into account the determinants of health related to the quality of populations' living environments and provides assistance in public policy decision-making. Ultimately, the aim is to develop measures likely to reduce exposure and prevent health risks and damage to the most vulnerable populations, both in their physical environment and in their living environment, including the economic and social determinants.


Assuntos
Carcinógenos Ambientais/toxicidade , Exposição Ambiental/efeitos adversos , Neoplasias/etiologia , Causalidade , Saúde Ambiental , Humanos , Neoplasias/genética , Neoplasias/prevenção & controle , Fatores de Risco
3.
Int J Mol Sci ; 20(19)2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31623305

RESUMO

Worldwide, several million workers are employed in the various chromium (Cr) industries. These workers may suffer from a variety of adverse health effects produced by dusts, mists and fumes containing Cr in the hexavalent oxidation state, Cr(VI). Of major importance, occupational exposure to Cr(VI) compounds has been firmly associated with the development of lung cancer. Counterintuitively, Cr(VI) is mostly unreactive towards most biomolecules, including nucleic acids. However, its intracellular reduction produces several species that react extensively with biomolecules. The diversity and chemical versatility of these species add great complexity to the study of the molecular mechanisms underlying Cr(VI) toxicity and carcinogenicity. As a consequence, these mechanisms are still poorly understood, in spite of intensive research efforts. Here, we discuss the impact of Cr(VI) on the stress response-an intricate cellular system against proteotoxic stress which is increasingly viewed as playing a critical role in carcinogenesis. This discussion is preceded by information regarding applications, chemical properties and adverse health effects of Cr(VI). A summary of our current understanding of cancer initiation, promotion and progression is also provided, followed by a brief description of the stress response and its links to cancer and by an overview of potential molecular mechanisms of Cr(VI) carcinogenicity.


Assuntos
Carcinógenos Ambientais/farmacologia , Cromo/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Carcinógenos Ambientais/toxicidade , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Cromo/toxicidade , Dano ao DNA , Humanos , Neoplasias/etiologia , Neoplasias/metabolismo , Neoplasias/patologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética
4.
Arch Environ Contam Toxicol ; 77(4): 594-604, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31388704

RESUMO

A total of 39 lower brominated PBDE congeners in surface soils from the Yellow River Delta Natural Reserve (YRDNR) were analyzed in the present study. The total concentrations of PBDEs (ΣPBDEs) ranged from "not detected" to 0.732 ng g-1, with a mean concentration of 0.142 ng g-1. The concentrations of the ΣPBDEs displayed no correlation with the content of the total organic carbon in the YRDNR. The ΣPBDEs concentrations in the Experimental Area were significantly higher than that of the Buffer Area and Core Area, and ΣPBDEs in soils in the North were lower than that of the South. PentaBDEs and HexaBDEs were the most abundant homologues, and the occurrence of PBDEs in the YRDNR may be attributed to the debromination and long range transport of DecaBDEs. Even though the cancer risk and mass inventory of PBDEs in the present study area were estimated to be very low, due to the widespread presence of PBDEs and the particularity of the natural reserve, vigilance should not be let up on the issue of environmental contamination caused by these compounds despite the gradual phase out of their commercial products in the world.


Assuntos
Éteres Difenil Halogenados/análise , Poluentes do Solo/análise , Carcinógenos Ambientais/análise , Carcinógenos Ambientais/toxicidade , China , Conservação dos Recursos Naturais , Monitoramento Ambiental , Retardadores de Chama/análise , Éteres Difenil Halogenados/toxicidade , Humanos , Medição de Risco , Poluentes do Solo/toxicidade
5.
Med Hypotheses ; 131: 109303, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31443747

RESUMO

The problems of immunoprotection from the environmental chemical carcinogens are discussed. The main experimental argument pro active immunization against carcinogens is a possibility of specific mucosal antibodies (Abs) to inhibit the penetration of carcinogens from environment and to stimulate its excretion with the following decreasing of carcinogen-DNA adducts levels. Hypothesis of cancer immunostimulation after active immunization against carcinogens is based on a high cancer risk in persons with high levels of serum Abs specific to environmental carcinogens coupled with high levels of Abs to endogenous steroids stimulating the proliferation of target cells, for example, Abs to benzo[a]pyrene together with Abs to estradiol. The active immunization could increase the cancer risk much more in those persons. The passive immunization could be an alternative safe approach to avoid this problem.


Assuntos
Carcinógenos Ambientais/toxicidade , Neoplasias/prevenção & controle , Vacinação , Animais , Anticorpos/sangue , Especificidade de Anticorpos , Autoanticorpos/imunologia , Carcinógenos/toxicidade , Carcinógenos Ambientais/farmacocinética , Linhagem Celular Tumoral , Cocarcinogênese , Adutos de DNA/imunologia , Feminino , Haptenos/imunologia , Humanos , Imunização Passiva , Masculino , Camundongos , Camundongos Endogâmicos , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/prevenção & controle , Neoplasias Hormônio-Dependentes/induzido quimicamente , Neoplasias Hormônio-Dependentes/imunologia , Neoplasias Hormônio-Dependentes/prevenção & controle , Ratos , Ratos Endogâmicos , Risco , Esteroides/imunologia , Vacinação/efeitos adversos
7.
Toxicol Lett ; 314: 133-141, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31325633

RESUMO

Hexavalent chromium (Cr(VI)) compounds are classified as carcinogenic to humans. Whereas chromium measurements in urine and plasma attest to the last few hours of total chromium exposure (all oxidation states of chromium), chromium in red blood cells (RBC) is attributable specifically to Cr(VI) exposure over the last few days. Before recommending Cr in RBC (CrIE) as a biological indicator of Cr(VI) exposure, in vivo studies must be undertaken to assess its reliability. The present study examines the kinetics of Cr(VI) in rat after a single intravenous dose of ammonium dichromate. Chromium levels were measured in plasma, red blood cells and urine. The decay of the chromium concentration in plasma is one-phase-like (with half-life time of 0.55 day) but still measurable two days post injection. The excretion of urinary chromium peaks between five and six hours after injection and shows large variations. Intra-erythrocyte chromium (CrIE) was very constant up to a minimum of 2 days and half-life time was estimated to 13.3 days. Finally, Cr(III) does not interfere with Cr(VI) incorporation in RBC. On the basis of our results, we conclude that, unlike urinary chromium, chromium levels in RBC are indicative of the amount of dichromate (Cr(VI)) in blood.


Assuntos
Carcinógenos Ambientais/administração & dosagem , Carcinógenos Ambientais/metabolismo , Cromo/administração & dosagem , Cromo/sangue , Eritrócitos/metabolismo , Administração Intravenosa , Animais , Biomarcadores/sangue , Biomarcadores/urina , Carga Corporal (Radioterapia) , Carcinógenos Ambientais/farmacocinética , Carcinógenos Ambientais/toxicidade , Cromo/farmacocinética , Cromo/toxicidade , Masculino , Modelos Biológicos , Oxirredução , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Especificidade da Espécie , Toxicocinética
8.
Toxicol Lett ; 313: 108-119, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31251971

RESUMO

Polychlorinated biphenyls (PCBs) are classic persistent organic pollutants (POPs) and are associated with the progression of many cancers, including liver cancer. The present study investigated the effect of 2,3'4,4',5-pentachlorobiphenyl (PCB118) on hepatocellular carcinoma cell proliferation and its underlying mechanisms. The results indicated that PCB118 exposure promotes the proliferation and glycolysis of hepatocellular carcinoma SMMC-7721 cells. Moreover, PCB118 exposure increased the expression level of pyruvate kinase M2 (PKM2) and its nuclear translocation, whereas treatment with PKM2 shRNA suppressed the induction of cell proliferation and glycolysis by PCB118. PCB118 stimulated reactive oxygen species (ROS) production by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Treatment with the antioxidants N-acetyl-L-cysteine (NAC) and superoxide dismutase (SOD) prevented PCB118-induced effects on PKM2, cell proliferation and glycolysis. Furthermore, we found that PCB118 activated NADPH oxidase through the aryl hydrocarbon receptor (AhR) in SMMC-7721 cells. Consistently, treatment with AhR shRNA suppressed PCB118-induced effects on PKM2, cell proliferation and glycolysis. Overall, these results indicated that PCB118 promotes HCC cell proliferation via PKM2-dependent upregulation of glycolysis, which is mediated by AhR/NADPH oxidase-induced ROS production.


Assuntos
Carcinógenos Ambientais/toxicidade , Carcinoma Hepatocelular/enzimologia , Proteínas de Transporte/metabolismo , Proliferação de Células/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Neoplasias Hepáticas/enzimologia , Proteínas de Membrana/metabolismo , Bifenilos Policlorados/toxicidade , Hormônios Tireóideos/metabolismo , Transporte Ativo do Núcleo Celular , Fatores de Transcrição Hélice-Alça-Hélice Básicos/agonistas , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/patologia , Proteínas de Membrana/genética , NADPH Oxidases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores de Hidrocarboneto Arílico/agonistas , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Hormônios Tireóideos/genética
9.
Environ Geochem Health ; 41(6): 2821-2843, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31190126

RESUMO

Analysis of soil samples around pristine and major gold-mining areas in Ghana was carried out for heavy metals as part of a larger soil contamination and metal background study. The surface soil samples were digested using microwave digester (aqua regia) and analyzed with ICP-MS for As, Cd, Hg, Zn, Co, Cu, Mn, Fe, Al, V, Cr, and Pb. The average concentrations (mg/L) for the metals ranged from 0.01 ± 0.01 (Cd) to 86,859.36 ± 47.07 (Fe) for the pristine sites, and 0.01 ± 0.01 (Cd) to 59,006.95 ± 79.06 (Fe) for the mining sites. Mercury was below the detection limit of the analytical instrument (0.029). The concentrations of heavy metals from this study were used to assess their contamination levels, and health risks. The results showed that, the metals ranked by severity of health risks as As > Pb > Cr > Cd. Principal component analysis (PCA) and cluster analysis showed two groupings with the PCA showing metals variability explained by 79.02%. Results from the PCA and Cluster analysis indicate anthropogenic sources of the metals which may be emanating from gold-mining activities. Results from multi-criteria ranking and pattern recognition employing PROMETHEE and GAIA revealed major contribution of the metals from the mining sites with metal variability explained by 72.83%. This is the first time a multi-criteria approach is employed to characterize heavy metal contamination in Ghana, and the study nevertheless brought to light the impact of mining on human health and the environment with implications for other mineral areas around the globe.


Assuntos
Metais Pesados/análise , Mineração , Medição de Risco/métodos , Poluentes do Solo/análise , Carcinógenos Ambientais/análise , Carcinógenos Ambientais/toxicidade , Análise por Conglomerados , Monitoramento Ambiental/métodos , Gana , Ouro , Humanos , Limite de Detecção , Espectrometria de Massas/métodos , Mercúrio/análise , Metais Pesados/toxicidade , Poluentes do Solo/toxicidade
10.
Environ Sci Pollut Res Int ; 26(18): 18181-18190, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31037529

RESUMO

Chromium is used in daily life and has a wide range of functions. It plays an important role in protein synthesis and carbohydrate and lipid metabolism. Chromium is found in trivalent Cr(III) and hexavalent Cr(VI) form; Cr(III) is relatively stable and intimately participates with many phenomena of metabolisms. Whereas, Cr(VI) is toxic, which results in growth inhibition and leading to changes in components of antioxidant systems as well as secondary metabolites. However, the molecular mechanism that is involved in Cr (VI)-induced hepatotoxicity is still unclear. For this purpose, 40 chickens were randomly assigned into two groups: the normal group (feeding the basic diet and clear water), the chromium group (16%LD50, 74.24 mg/kg/day K2Cr2O7 ). The samples were subjected to pathological examination and UHPLC-QE-MS non-target metabolomics method for metabolomics analysis of broiler liver using principal component analysis (PCA) and partial least squares discriminant analysis (OPLS-DA). The central venous cells of the broiler liver in the chromium poisoning group showed turbidity and flaky necrosis, nuclear condensation, nuclear rupture, and even nuclear dissolution. The differential metabolite analysis between the chromium poisoning and the control group showed that 32 differential metabolites were upregulated and 15 were downregulated in positive ion mode. Whereas,17 differential metabolites were downregulated, and 35 were downregulated in negative ion mode (P ≤ 0.05). The potential marker substances are oleic acidamide, farnesylacetone, betaine, taurine, choline, and galactinol. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that the lipid metabolism, carbohydrate metabolism, nucleotide metabolism, amino acid metabolism, energy metabolism, membrane transport, digestive system, and nervous system were the most important metabolic pathways in the liver. This study provides a theoretical basis for the future understanding of the pathogenesis of chromium poisoning and a new insight of the subsequent molecular mechanism of chromium hepatotoxicity.


Assuntos
Carcinógenos Ambientais/toxicidade , Galinhas , Cromo/toxicidade , Fígado/efeitos dos fármacos , Metabolômica , Animais , Biomarcadores/metabolismo , Metabolismo dos Carboidratos , Galinhas/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Redes e Vias Metabólicas , Distribuição Aleatória
11.
Chem Res Toxicol ; 32(5): 887-898, 2019 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-30990016

RESUMO

Metabolism of 1,3-butadiene, a known human and rodent carcinogen, results in formation of reactive epoxides, a key event in its carcinogenicity. Although mice exposed to 1,3-butadiene present DNA adducts in all tested tissues, carcinogenicity is limited to liver, lung, and lymphoid tissues. Previous studies demonstrated that strain- and tissue-specific epigenetic effects in response to 1,3-butadiene exposure may influence susceptibly to DNA damage and serve as a potential mechanism of tissue-specific carcinogenicity. This study aimed to investigate interindividual variability in the effects of 1,3-butadiene using a population-based mouse model. Male mice from 20 Collaborative Cross strains were exposed to 0 or 635 ppm 1,3-butadiene by inhalation (6 h/day, 5 days/week) for 2 weeks. We evaluated DNA damage and epigenetic effects in target (lung and liver) and nontarget (kidney) tissues of 1,3-butadiene-induced carcinogenesis. DNA damage was assessed by measuring N-7-(2,3,4-trihydroxybut-1-yl)-guanine (THB-Gua) adducts. To investigate global histone modification alterations, we evaluated the trimethylation and acetylation of histones H3 and H4 across tissues. Changes in global cytosine DNA methylation were evaluated from the levels of methylation of LINE-1 and SINE B1 retrotransposons. We quantified the degree of variation across strains, deriving a chemical-specific human variability factor to address population variability in carcinogenic risk, which is largely ignored in current cancer risk assessment practice. Quantitative trait locus mapping identified four candidate genes related to chromatin remodeling whose variation was associated with interstrain susceptibility. Overall, this study uses 1,3-butadiene to demonstrate how the Collaborative Cross mouse population can be used to identify the mechanisms for and quantify the degree of interindividual variability in tissue-specific effects that are relevant to chemically induced carcinogenesis.


Assuntos
Butadienos/toxicidade , Adutos de DNA/metabolismo , Epigênese Genética/efeitos dos fármacos , Animais , Carcinógenos Ambientais/toxicidade , Adutos de DNA/química , Adutos de DNA/genética , Metilação de DNA/efeitos dos fármacos , Guanina/análogos & derivados , Guanina/química , Histonas/metabolismo , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Masculino , Camundongos , Mutagênicos/toxicidade
12.
Biomarkers ; 24(4): 379-388, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30821509

RESUMO

Context: Fumonisins (FNs), a group of mycotoxins produced mainly by Fusarium species, are ubiquitous food contaminants, especially for maize. Fumonisin B1 (FB1) caused severe toxicities in farm animals, induced kidney and liver tumours in rodents and is associated with many human adverse health effects, including oesophageal cancer. International Agency for Research on Cancer (IARC) categorizes FB1 as a possible human carcinogen (Group 2B). Inhibition of ceramide synthesis and disruption of sphingolipids metabolism are well studied as the major mechanisms of FB1-induced toxicity. Increases in sphinganine (Sa) and decrease in sphingosine (So) levels and their ratio are validated biomarkers of FB1 effects. Methods: In this study, we measured urinary levels of Sa, So and Sa/So in 284 children aged 1-14 years who consume maize as a staple diet. Exfoliated cells from urine were processed and sphingolipids quantified by High Pressure Liquid Chromatography. Results and conclusions: Sa and So were detectable in 95.07% and 98.94% of samples, respectively. Creatinine adjusted mean levels and standard deviation of Sa, So and Sa/So ratio were 1.23 ± 2.18, 4.99 ± 8.3 and 0.296 ± 0.587 nM. These results further confirmed the findings in studies with human adults, i.e. urinary Sa, So levels and Sa/So ratio are good biomarkers to assess FNs exposure in children.


Assuntos
Arachis/química , Carcinógenos Ambientais/toxicidade , Fumonisinas/toxicidade , Esfingosina/análogos & derivados , Esfingosina/urina , Zea mays/química , Adolescente , Biomarcadores/urina , Carcinógenos Ambientais/metabolismo , Criança , Pré-Escolar , Creatinina/urina , Dieta , Feminino , Contaminação de Alimentos , Fumonisinas/metabolismo , Humanos , Lactente , Quênia , Metabolismo dos Lipídeos , Masculino
13.
Chemosphere ; 224: 734-742, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30851525

RESUMO

Chromium (Cr) is a well-known toxic metal, but studies on Cr toxicity to soil-dwelling springtails are fairly limited, and did not consider the effects of various soil properties and long aging time. To address this, the chronic toxicity of Cr(VI) to survival and reproduction of model organism-Folsomia candida were evaluated in the laboratory studies. The results showed that compared to the soils aged only for 2 and 21 d, the concentrations inhibiting 50% reproduction (EC50) significantly increased by 2.8-5.2 fold and 1.7-2.6 fold, the concentrations causing 50% mortality (LC50) were higher than the highest test concentration in four soils aged for 150 d. Furthermore, the aging effects correlated significantly with soil amorphous Fe oxides. The EC50 values of Cr significantly differed in ten soils aged for 150 d, ranging from 27 to 512 mg kg-1, which were associated with the variations in reduction and sorption capacity in different soils. Regression analysis indicated that soil clay was the most important single factor predicting soil Cr toxicity to reproduction, and the inclusion of cation exchange capacity in the clay regression could best explain the toxicity variance (87.2%). Additionally, soil pH, organic matter and amorphous Fe oxides could also well explain the toxicity variance (>55%).


Assuntos
Artrópodes/efeitos dos fármacos , Carcinógenos Ambientais/toxicidade , Cromo/análise , Cromo/toxicidade , Poluentes do Solo/análise , Poluentes do Solo/toxicidade , Animais , Carcinógenos Ambientais/análise , Dose Letal Mediana , Óxidos/análise , Reprodução/efeitos dos fármacos , Solo/química
15.
Environ Toxicol Pharmacol ; 66: 126-132, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30677706

RESUMO

Hexavalent chromium [Cr(VI)] is one of the most common environmental carcinogens, which is associated with DNA damage, genetic instability and increase the risk of cancer development. However, the mechanisms of genetic damage induced by Cr(VI) remains to be thoroughly illustrated. A molecular epidemiological study was conducted on 120 chromate exposed workers and 97 controls. Results indicated that,the rs12432907 of XRCC3 carrying T allele, the rs144848 of BRCA2 with C allele and the rs1805800 of NBS1 with genotype(TT) of individuals were associated with lower genetic damage, while the rs2295152 of XRCC3 carrying T allele, the rs13312986 (CC and CT genotypes) and the rs2697679 of NBS1 with A allele were associated with higher genetic damage in workers exposed to chromate. The interaction of chromate exposure with rs2295152 of XRCC3 had a significant effect on micronuclei frequency (MNF). The gene polymorphisms in homologous recombination repair pathway could modulate chromate-induced genetic damage.


Assuntos
Carcinógenos Ambientais/toxicidade , Cromo/toxicidade , Proteínas de Ligação a DNA/genética , Exposição Ocupacional/efeitos adversos , Adulto , Dano ao DNA , Feminino , Genótipo , Humanos , Linfócitos/metabolismo , Masculino , Micronúcleos com Defeito Cromossômico , Polimorfismo Genético , Reparo de DNA por Recombinação
16.
Environ Geochem Health ; 41(1): 481-505, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29623519

RESUMO

This study was initiated to develop a model specialized to conduct human risk assessments (HRAs) of abandoned metal mine areas in Korea. The Korean guideline (KG) model used in study was formulated via modification of the original Korean guidelines on HRAs of soil contamination. In addition, the newly developed model was applied to the HRAs of two abandoned metal mines contaminated with arsenic (As) and heavy metals (Cd, Cu, Pb, and Zn). The results of the KG model were compared with those of two internationally renowned models [Contaminated land exposure assessment (CLEA) and CSOIL models]. The HRA results of the three models indicated that the areas of concern were unsafe when it came to both carcinogenic and non-carcinogenic hazards. Furthermore, the hazards in both areas were mostly attributed to As and the predominant exposure pathways were identified as crop intake in the KG model and surface soil dermal contact in CLEA and CSOIL models. Accordingly, measures to protect against As exposure should be established immediately to prevent adverse health effects on inhabitants in these areas. A comparison of HRA results revealed significant differences between KG, CLEA, and CSOIL models due to the various types of exposure pathways, contaminants, and input data, such as exposure factors and receptor parameters. This study suggests that set-up of an exposure scenario is crucial for the successful performance of HRAs, and the most relevant HRA model should be deliberately selected to attain risk assessment goals.


Assuntos
Arsênico/toxicidade , Monitoramento Ambiental/métodos , Metais Pesados/toxicidade , Modelos Teóricos , Poluentes do Solo/toxicidade , Carcinógenos Ambientais/toxicidade , Humanos , Mineração , República da Coreia , Medição de Risco
17.
Environ Geochem Health ; 41(1): 225-247, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30171477

RESUMO

MicroRNAs (miRNAs) are a class of small, noncoding RNA species that play crucial roles across many biological processes and in the pathogenesis of major diseases, including cancer. Recent studies suggest that the expression of miRNA is altered by certain environmental chemicals, including metals, organic pollutants, cigarette smoke, pesticides and carcinogenic drugs. In addition, extensive studies have indicated the existence and importance of miRNA in different cancers, suggesting that cancer-related miRNAs could serve as potential markers for chemically induced cancers. The altered expression of miRNA was considered to be a vital pathogenic role in xenobiotic-induced cancer development. However, the significance of miRNA in the etiology of cancer and the exact mechanisms by which environmental factors alter miRNA expression remain relatively unexplored. Hence, understanding the interaction of miRNAs with environmental chemicals will provide important information on mechanisms underlying the pathogenesis of chemically induced cancers, and effectively diagnose and treat human cancers resulting from chronic or acute carcinogen exposure. This study presents the current evidence that the miRNA deregulation induced by various chemical carcinogens, different cancers caused by environmental carcinogens and the potentially related genes in the onset or progression of cancer. For each carcinogen, the specifically expressed miRNA may be considered as the early biomarkers of the cancer process. In this review, we also summarize various target genes of the altered miRNA, oncogenes or anti-oncogenes, and the existing evidence regarding the gene regulation mechanisms of cancer caused by environmentally induced miRNA alteration. The future perspective of miRNA may become attractive targets for the diagnosis and treatment of carcinogen-induced cancer.


Assuntos
Carcinogênese/induzido quimicamente , Carcinógenos Ambientais/toxicidade , Poluentes Ambientais/toxicidade , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/fisiologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/fisiologia , Genes Neoplásicos/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/induzido quimicamente
18.
Oncol Rep ; 41(2): 981-988, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30431128

RESUMO

The role of perfluorodecanoic acid (PFDA) in gastric carcinogenesis and its mechanism remains unknown. Our previous research revealed that PFDA regulated the growth of human gastric cells. However, its core molecules and basic mechanisms are still not clear. In the present study, cDNA microarrays were used to determine mRNA changes in AGS cells after treatment with PFDA. DAVID analysis of the genes with >2­fold increased expression in microarray data revealed five genes which were involved in cancer pathways. The most upregulated gene was cIAP2, whose upregulation in AGS was confirmed by western blot analysis and quantitative PCR (qPCR) analyses. In order to investigate the role of cIAP2 in cell proliferation, cIAP2 siRNA was employed to regulate cIAP2 expression following PFDA treatment. The results revealed that the growth rate of cIAP2­knockdown cells was reduced by about 50% compared to the control. Given that our previous flow cytometric assays revealed no significant change (3.7 vs. 6.4%) in the percentage of apoptotic cells when PFDA was added to the medium and cIAP2 expression was upregulated, we next applied flow cytometry to assess whether cIAP2 would lead to cell cycle variations. The research data revealed that the proportion of cells in the G1, S and G2 phases was not significantly altered with the decrease of cIAP2 expression. Finally, the role of cIAP2 in AGS cell senescence was investigated, and the results indicated that cell senescence was significantly increased in the cIAP2 siRNA group in comparison to the control siRNA group. Since p53 has been identified as a tumor suppressor and its molecular alterations are common in different human tumors, we investigated the relationship of p53 with cIAP2. The experimental results demonstrated that cIAP2 regulated the expression of p53 and thus was likely to be a potential mechanism for PFDA­induced growth promotion. Overall, the results revealed that PFDA may suppress cellular senescence induced by p53 through the regulation of cIAP2 protein expression.


Assuntos
Proteína 3 com Repetições IAP de Baculovírus/metabolismo , Carcinógenos Ambientais/toxicidade , Senescência Celular/efeitos dos fármacos , Ácidos Decanoicos/toxicidade , Poluentes Ambientais/toxicidade , Fluorcarbonetos/toxicidade , Neoplasias Gástricas/patologia , Proteína 3 com Repetições IAP de Baculovírus/genética , Carcinogênese/induzido quimicamente , Carcinogênese/patologia , Linhagem Celular Tumoral , Células Epiteliais , Perfilação da Expressão Gênica/métodos , Humanos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Estômago/citologia , Neoplasias Gástricas/induzido quimicamente , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacos
19.
Sci Total Environ ; 655: 622-632, 2019 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-30476843

RESUMO

Compounds containing hexavalent chromium [Cr(VI)] were Group I human carcinogens which were mutagenic and can induce DNA damage. Cr(VI) exposure could cause a lot of changes in mRNA, protein and microRNA expression as well as DNA methylation. There were still few studies on the role of long non-coding RNA (lncRNA) in the carcinogenic process of Cr(VI). In current study, lncRNA expression profiling and bioinformatics analysis in 16HBE cells treated by Cr(VI) were performed. The cell counting kit-8 (CCK-8) assay and the comet assay were done to assess the cell viability and DNA damage in Cr(VI)-treated 16HBE cells respectively. The lncRNA expression profile was performed by Arraystar Microarray V3.0 in 16HBE cells treated with 0.00 and 10.00 µmol/L Cr(VI). Real-time quantitative polymerase chain reaction (RT-qPCR) was applied to verify some significantly altered lncRNAs. Gene ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) analysis and mRNA-lncRNA network analysis were conducted to identify related biological processes, signal pathway and critical lncRNAs. It was found that Cr(VI) could induce cells viability decline and alter lncRNA expression profile of 16HBE cells. 1868 lncRNAs were significantly up-regulated and 2203 lncRNAs were significantly down-regulated which formed a complex regulation network. With the increase of Cr(VI) concentration, some lncRNAs increased or decreased gradually. The differentially expressed LncRNA profiling induced by Cr(VI) were associated with immune response, cell cycle, DNA damage and repair and so on. RP11-388M20.9 and AC092620.3 were nonlinearly decreasing with the change of the DNA content of comet tails (Tail DNA), tail length (TLL), tail moment (TM) and Olive Tail Moment (OTM), and the fitting results of Tail DNA and TM were statistically significant (P < 0.05). It was possible for RP11-388M20.9 to regulate DNA damage by interacting with the target gene after Cr(VI) exposure, and was likely to be a potential biomarker of DNA damage in Cr(VI)-treated 16HBE cells.


Assuntos
Carcinógenos Ambientais/toxicidade , Cromo/toxicidade , Dano ao DNA/efeitos dos fármacos , Perfilação da Expressão Gênica , Expressão Gênica/efeitos dos fármacos , RNA Longo não Codificante/genética , Linhagem Celular Transformada , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Biologia Computacional , Relação Dose-Resposta a Droga , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , RNA Mensageiro/genética , Reprodutibilidade dos Testes , Transdução de Sinais/genética
20.
Environ Toxicol ; 34(4): 355-363, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30520250

RESUMO

In the present study, the modulatory effect of phytol against benzo(a)pyrene [B(a)P] induced lung carcinogenesis was investigated in Swiss albino mice. During the experimental period, phytol treatment showed no adverse toxic effect and mortality to the experimental animals. Lung tumor was observed in B(a)P treated group and also in animals post-treated with low concentration (50 mg/kg) of phytol. No neoplastic changes were observed in the lung tissue of the animals treated with the maximum dose of phytol (100 mg/kg). An elevated level of antioxidant enzymes combined with macromolecular damage (lipid peroxidation, protein carbonyl content) was observed upon B(a)P treatment whereas, phytol restored the level of antioxidant enzymes which were comparable to the vehicle control group. Moreover, administration of B(a)P induced apoptosis, as observed by the highest expression of Bax, caspase-3, and caspase-9 proteins in lung tissue of B(a)P alone treated animals. However, phytol treatment reduced the expression of Bax, caspase-3, and caspase-9 protein and maintained the constant expression of anti-apoptotic protein Bcl-2. These observations positively reveal that phytol regulates the antioxidant enzymes and thereby protects the cells against B(a)P induced carcinogenesis without showing any adverse toxic effect to the animals.


Assuntos
Anticarcinógenos/farmacologia , Apoptose/efeitos dos fármacos , Benzo(a)pireno/toxicidade , Carcinógenos Ambientais/toxicidade , Neoplasias Pulmonares/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Fitol/farmacologia , Animais , Antioxidantes/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Neoplasias Pulmonares/induzido quimicamente , Masculino , Camundongos , Carbonilação Proteica/efeitos dos fármacos
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