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1.
Food Chem ; 334: 127402, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32711260

RESUMO

In this study, heavy metals including Cr, Mn, Co, Ni, Cu, Zn, As, and Cd in 55 Thai local rice (4 varieties) were measured using ICP-MS. Health risks were estimated from various Thai population groups, classified according to ages and genders. The potential impact on Thai population who consumed Thai local rice contained heavy metals was assessed by means of probabilistic approach. The hazard quotient (HQ) for non-carcinogenic risks from heavy metal exposure was below the threshold limit of 1 for all rice varieties except Mn in Pka Am Pun rice and As in Pka Am Pun rice, Jek Chuey Sao Hai rice, and Leb Nok rice. Only the hazard index (HI) for consumption of Khaowong Kalasin sticky rice was below 1. The maximum cancer probabilities over the lifetime consumption of Thai local rice were in the range of 5 in 10,000 to 3 in 1000 chances in developing cancer.


Assuntos
Exposição Dietética/análise , Contaminação de Alimentos/análise , Metais Pesados/análise , Oryza/química , Adolescente , Adulto , Idoso , Carcinógenos/análise , Carcinógenos/toxicidade , Criança , Pré-Escolar , Exposição Dietética/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Tailândia , Adulto Jovem
2.
PLoS One ; 15(10): e0239338, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33085669

RESUMO

OBJECTIVES: Up to 10% of Bladder Cancers may arise following occupational exposure to carcinogens. We hypothesised that different cancer phenotypes reflected different patterns of occupational exposure. METHODS: Consecutive participants, with bladder cancer, self-completed a structured questionnaire detailing employment, tasks, exposures, smoking, lifestyle and family history. Our primary outcome was association between cancer phenotype and occupational details. RESULTS: We collected questionnaires from 536 patients, of whom 454 (85%) participants (352 men and 102 women) were included. Women were less likely to be smokers (68% vs. 81% Chi sq. p<0.001), but more likely than men to inhale environmental tobacco smoke at home (82% vs. 74% p = 0.08) and use hair dye (56% vs. 3%, p<0.001). Contact with potential carcinogens occurred in 282 (62%) participants (mean 3.1 per worker (range 0-14)). High-grade cancer was more common than low-grade disease in workers from the steel, foundry, metal, engineering and transport industries (p<0.05), and in workers exposed to crack detection dyes, chromium, coal/oil/gas by-products, diesel fumes/fuel/aircraft fuel and solvents (such as trichloroethylene). Higher staged cancers were frequent in workers exposed to Chromium, coal products and diesel exhaust fumes/fuel (p<0.05). Various workers (e.g. exposed to diesel fuels or fumes (Cox, HR 1.97 (95% CI 1.31-2.98) p = 0.001), employed in a garage (HR 2.19 (95% CI 1.31-3.63) p = 0.001), undertaking plumbing/gas fitting/ventilation (HR 2.15 (95% CI 1.15-4.01) p = 0.017), undertaking welding (HR 1.85 (95% CI 1.24-2.77) p = 0.003) and exposed to welding materials (HR 1.92 (95% CI 1.27-2.91) p = 0.002)) were more likely to have disease progression and receive radical treatment than others. Fewer than expected deaths were seen in healthcare workers (HR 0.17 (95% CI 0.04-0.70) p = 0.014). CONCLUSIONS: We identified multiple occupational tasks and contacts associated with bladder cancer. There were some associations with phenotype, although our study design precludes robust assessment.


Assuntos
Doenças Profissionais/patologia , Exposição Ocupacional/análise , Neoplasias da Bexiga Urinária/patologia , Idoso , Poluentes Ocupacionais do Ar/toxicidade , Carcinógenos/toxicidade , Estudos Transversais , Emprego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Doenças Profissionais/mortalidade , Fenótipo , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Fumar , Inquéritos e Questionários , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/mortalidade , Emissões de Veículos/toxicidade
3.
Cent Eur J Public Health ; 28 Suppl: S43-S46, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33069180

RESUMO

OBJECTIVES: Acrylamide is a toxic compound that can be found it both occupational and non-occupational environments. This study focuses on its sources and health effects of its exposure. METHODS: Adverse effects of acrylamide, especially carcinogenic, genotoxic, and teratogenic were reported in many studies conducted on animals. Neurotoxicity was reported in workers exposed to acrylamide in the occupational environment. Another important source of populations' exposure to acrylamide is their nutrition. RESULTS: This study focuses on humans' exposure to acrylamide from various sources and its harmful effects on their health. CONCLUSIONS: Dietary intake of acrylamide, as well as occupational exposure, cigarette smoking, cosmetics usage and other environmental sources could have a significant effect on human health.


Assuntos
Acrilamida , Exposição Ocupacional , Acrilamida/toxicidade , Animais , Carcinógenos/toxicidade , Dano ao DNA/efeitos dos fármacos , Humanos , Estado Nutricional/efeitos dos fármacos , Exposição Ocupacional/efeitos adversos
4.
Ecotoxicol Environ Saf ; 203: 111055, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888617

RESUMO

The pollution level of potentially toxic elements (PTEs) in surface soils is detrimental to the ecosystem and human health. In this research, various indices such as an index of geo-accumulation (Igeo), contamination factor (CF), degree of contamination (DC), and principal component analysis (PCA) were implemented to identify and evaluate the soil PTEs pollution; and then human health risk assessment model used to establish the link between heavy metals pollution and human health in the urban region of south India. Results exhibited that the mean concentration of Cr, Cu, Ni and Zn were found to be 1.45-6.03 times greater than the geochemical background values. Cr and Cu were the most profuse PTEs measured in the soils. The pollution indices suggest that soil of the study region is mainly moderate to highly polluted. The non-carcinogenic health risk assessment proposed by the United States Environmental Protection Agency (USEPA) suggested the mean hazard indices (HIs) were below one which denotes no significant of non-carcinogenic risks to both children and adults. Furthermore, carcinogenic risk assessment results advised ~80% of cancer risk was caused by Cr contents, while other heavy metals indicate that neither children nor adults in the study region were of carcinogenic risks.


Assuntos
Carcinógenos/análise , Monitoramento Ambiental/métodos , Substâncias Perigosas/análise , Metais Pesados/análise , Poluentes do Solo/análise , Solo/química , Adulto , Carcinógenos/toxicidade , Criança , Ecossistema , Substâncias Perigosas/toxicidade , Humanos , Índia , Metais Pesados/toxicidade , Medição de Risco , Poluentes do Solo/toxicidade , Estados Unidos , United States Environmental Protection Agency , Urbanização
5.
Environ Sci Pollut Res Int ; 27(34): 42405-42423, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32875453

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic compounds which are emitted through incomplete combustion of organic materials, fossil fuels, consumption of processed meat, smoked food, and from various industrial activities. High molecular mass and mobility make PAHs widespread and lethal for human health. A cellular system in human detoxifies these toxicants through specialized enzymatic machinery called xenobiotic-metabolizing (CYP450) and phase-II (GSTs) enzymes (XMEs). These metabolizing enzymes include cytochromes P450 family (CYP1, CYP2), glutathione s-transferases, and ALDHs. Gene polymorphisms in XMEs encoding genes can compromise their metabolizing capacity to detoxify ingested carcinogens (PAHs etc.) that may lead to prolong and elevated exposure to ingested toxicants and may consequently lead to cancer. Moreover, PAHs can induce cancer through reprograming XMEs' gene functions by altering their epigenetic markers. This review article discusses possible interplay between individual's gene polymorphism in XMEs' genes, their altered epigenetic markers, and exposure to PAHs in cancer susceptibility in Pakistan.


Assuntos
Neoplasias , Hidrocarbonetos Policíclicos Aromáticos , Carcinógenos/análise , Carcinógenos/toxicidade , Exposição Ambiental , Monitoramento Ambiental , Humanos , Neoplasias/induzido quimicamente , Neoplasias/genética , Paquistão , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Polimorfismo Genético
6.
Mutat Res ; 856-857: 503218, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32928366

RESUMO

The Ames microplate format (MPF™) is a miniaturized version of the plate agar Ames tests that takes advantage of a liquid microplate approach in 384-well plates with a color change-based readout. This method, already compared to the Ames test in Petri dishes, is used to assess the genotoxic potential of a variety of test items, including (but not limited to) chemicals, environmental samples, and drug candidates. 61 chemicals were selected from the updated recommended lists of genotoxic and non-genotoxic chemicals for assessment of the performance of new or improved genotoxicity tests and tested in up to five bacterial strains. The agreement with the data from the scientific literature (over 90%) confirms the reliability of the Ames MPF™ as a cost-effective and 3R-compliant alternative to the regulatory Ames test that allows to predict and evaluate chemicals' mutagenicity in a faster, less laborious and, if available, automatable manner.


Assuntos
Carcinógenos/farmacologia , Dano ao DNA/efeitos dos fármacos , Testes de Mutagenicidade/métodos , Mutagênicos/farmacologia , Carcinógenos/toxicidade , Escherichia coli/efeitos dos fármacos , Humanos , Microfluídica/métodos , Mutagênicos/toxicidade , Reprodutibilidade dos Testes
7.
Toxicol Lett ; 332: 171-180, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32659470

RESUMO

The pregnane X receptor (PXR) has been established to induce chemoresistance and metabolic diseases. Ochratoxin A (OTA), a mycotoxin, decreases the expression of PXR protein in human primary hepatocytes. OTA is chlorinated and has a methylated lactone ring. Both structures are associated with OTA toxicity. The study was to test the hypothesis that structural modifications differentially impact PXR blocking activity over cytotoxicity. To test this hypothesis, OTA-M and OTA-Cl/M were synthesized. OTA-M lacked the methyl group of the lactone-ring, whereas OTA-Cl/M had neither the methyl group nor the chlorine atom. The blocking activity of PXR activation was determined in a stable cell line, harboring both PXR (coding sequence) and its luciferase element reporter. OTA-Cl/M showed the highest blocking activity, followed by OTA-M and OTA. OTA-Cl/M was 60 times as potent as the common PXR blocker ketoconazole based on calculated IC50 values. OTA-Cl/M decreased by 90 % the expression of PXR protein and was the least cytotoxic among the tested compounds. Molecular docking identified that OTA and its derivatives interacted with different sets of residues in PXR, providing a molecular basis for selectivity. Excessive activation of PXR has been implicated in chemoresistance and metabolic diseases. Downregulation of PXR protein expression likely delivers an effective mechanism against structurally diverse PXR agonists.


Assuntos
Carcinógenos/química , Carcinógenos/toxicidade , Ocratoxinas/química , Ocratoxinas/toxicidade , Receptor de Pregnano X/antagonistas & inibidores , Sobrevivência Celular , Desmetilação , Expressão Gênica/efeitos dos fármacos , Células HEK293 , Halogenação , Humanos , Cetoconazol/farmacologia , Simulação de Acoplamento Molecular , Receptor de Pregnano X/biossíntese
8.
Mol Carcinog ; 59(9): 1088-1099, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32673443

RESUMO

Manganese superoxide dismutase (SOD-2), an important primary antioxidant enzyme located in mitochondria, plays a critical role in tumor progression. Reportedly, the proinflammatory cytokine, tumor necrosis factor (TNF)-α, can increase SOD-2 expression in a human lung adenocarcinoma cell line in vitro, indicating that TNF-α-mediated inflammation may regulate SOD-2 expression, which may be related to cancer promotion. Using a urethane-induced inflammation-driven lung adenocarcinoma (IDLA) mice model, we investigated whether and how TNF-α-mediated inflammation upregulated SOD-2 expression in lung adenocarcinoma. Our results showed that SOD-2 was mostly expressed on surfactant protein-C+ AT-II cells (alveolar type II cell) and tumor cells in IDLA mice, which were surrounded by CD68+ macrophages. Blocking TNF-α-dependent inflammation downregulated SOD-2 expression in inflamed lung tissues at the protumor stage and also inhibited SOD-2 expression in tumor cells in the IDLA model. In human lung adenocarcinoma, both the number of infiltrating CD68+ macrophages and TNF-α expression correlated positively with SOD-2 expression, which is related to lymph node metastasis and TNM stage. We collected the conditioned medium from lipopolysaccharide-activated phorbol myristate acetate-induced THP1 (M1) cells to stimulate A549 and H1299 cells and observed that THP1-M1 upregulated SOD-2 by secreting TNF-α. Blocking SOD-2 expression significantly inhibited TNF-α-induced cell proliferation in A549 and H1299 cells in vitro. Thus, TNF-α-mediated lung inflammation can upregulate SOD-2 expression in lung adenocarcinoma, and macrophages contribute to SOD-2 upregulation by secreting TNF-α.


Assuntos
Adenocarcinoma de Pulmão/patologia , Proliferação de Células , Neoplasias Pulmonares/patologia , Pneumonia/complicações , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Uretana/toxicidade , Adenocarcinoma de Pulmão/etiologia , Adenocarcinoma de Pulmão/metabolismo , Animais , Apoptose , Carcinógenos/toxicidade , Citocinas , Feminino , Humanos , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pneumonia/induzido quimicamente , Pneumonia/metabolismo , Células Tumorais Cultivadas
9.
Mutat Res ; 854-855: 503199, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32660827

RESUMO

The bacterial reverse mutation test (Ames test) is the most commonly used genotoxicity test; it is a primary component of the chemical safety assessment data required by regulatory agencies worldwide. Within the current accepted in vitro genotoxicity test battery, it is considered capable of revealing DNA reactivity, and identifying substances that can produce gene mutations via different mechanisms. The previously published consolidated EURL ECVAM Genotoxicity and Carcinogenicity Database, which includes substances that elicited a positive response in the Ames test, constitutes a collection of data that serves as a reference for a number of regulatory activities in the area of genotoxicity testing. Consequently, we considered it important to expand the database to include substances that fail to elicit a positive response in the Ames test, i.e., Ames negative substances. Here, we describe a curated collection of 211 Ames negative substances, with a summary of complementary data available for other genotoxicity endpoints in vitro and in vivo, plus available carcinogenicity data. A descriptive analysis of the data is presented. This includes a representation of the chemical space formed by the Ames-negative database with respect to other substances (e.g. REACH registered substances, approved drugs, pesticides, etc.) and a description of the organic functional groups found in the database. We also provide some suggestions on further analyses that could be made.


Assuntos
Testes de Carcinogenicidade/normas , Carcinógenos/toxicidade , Bases de Dados Factuais/normas , Testes de Mutagenicidade/normas , Mutagênicos/toxicidade , Resultados Negativos/normas , Animais , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/genética , Gerenciamento de Dados/normas , Humanos
10.
J Environ Pathol Toxicol Oncol ; 39(1): 13-21, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32479009

RESUMO

Breast cancer is a widespread disease that affects women globally. Diagnostic processes and remedial approaches to breast carcinogenesis have improved in recent decades, but continuous survival of patients with breast carcinogenesis is still lacking due to increased cell proliferation. The aim of the present work is to explore the anticell proliferative effects of nobiletin (NOB) against 7,12-dimethylbenz[a]anthracene (DMBA)-treated mammary tumorigenesis in rats. We stimulate mammary carcinogenesis using oral gavage of DMBA (25 mg/kg body weight) mixed with olive oil (1 mL). This results in reduced body weight; increased liver marker enzymes such as alkaline phosphatase, acid phosphatase, aspartate aminotransferase, and alanine aminotransferase; and cell proliferative markers such as c-Jun, proliferating cell nuclear antigen, c-Fos, cyclin D1, and activating protein-1 (AP-1) in the DMBA-treated cancer-bearing animals. NOB administration improved body weight, significantly reduced hepatic marker enzymes, and altered histopathological changes. Furthermore, NOB efficiently reduced tumor cell proliferation markers in DMBA-induced mammary carcinogenesis. Overall, these results suggest that NOB has an anticell proliferative effect on DMBA-induced mammary cancer via modulation of the AP-1 signaling pathway.


Assuntos
9,10-Dimetil-1,2-benzantraceno/toxicidade , Antioxidantes/farmacologia , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Flavonas/farmacologia , Neoplasias Mamárias Experimentais/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Carcinógenos/toxicidade , Transformação Celular Neoplásica/efeitos dos fármacos , Feminino , Ratos , Ratos Sprague-Dawley , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo
12.
Mutat Res ; 853: 503195, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32522347

RESUMO

Recent years have witnessed an expansion of mutagenesis research focusing on experimentally modeled genome-scale mutational signatures of carcinogens and of endogenous processes. Experimental mutational signatures can explain etiologic links to patterns found in human tumors that may be linked to same exposures, and can serve as biomarkers of exposure history and may even provide insights on causality. A number of innovative exposure models have been employed and reported, based on cells cultured in monolayers or in 3-D, on organoids, induced pluripotent stem cells, non-mammalian organisms, microorganisms and rodent bioassays. Here we discuss some of the latest developments and pros and cons of these experimental systems used in mutational signature analysis. Integrative designs that bring together multiple exposure systems (in vitro, in vivo and in silico pan-cancer data mining) started emerging as powerful tools to identify robust mutational signatures of the tested cancer risk agents. We further propose that devising a new generation of cell-based models is warranted to streamline systematic testing of carcinogen effects on the cell genomes, while seeking to increasingly supplant animal with non-animal systems to address relevant ethical issues and accentuate the 3R principles. We conclude that the knowledge accumulating from the growing body of signature modelling investigations has considerable power to advance cancer etiology studies and to support cancer prevention efforts through streamlined characterization of cancer-causing agents and the recognition of their specific effects.


Assuntos
Carcinógenos/toxicidade , Mutagênese/efeitos dos fármacos , Mutação/efeitos dos fármacos , Neoplasias/induzido quimicamente , Animais , Análise Mutacional de DNA/métodos , Genoma Humano/efeitos dos fármacos , Genoma Humano/genética , Humanos , Mutagênese/genética , Mutação/genética
13.
Artigo em Inglês | MEDLINE | ID: mdl-32560183

RESUMO

Non-genotoxic hepatocarcinogens (NGHCs) can only be confirmed by 2-year rodent studies. Toxicogenomics (TGx) approaches using gene expression profiles from short-term animal studies could enable early assessment of NGHCs. However, high variance in the modulation of the genes had been noted among exposure styles and datasets. Expanding from our previous strategy in identifying consensus biomarkers in multiple experiments, we aimed to identify time-invariant biomarkers for NGHCs in short-term exposure styles and validate their applicability to long-term exposure styles. In this study, nine time-invariant biomarkers, namely A2m, Akr7a3, Aqp7, Ca3, Cdc2a, Cdkn3, Cyp2c11, Ntf3, and Sds, were identified from four large-scale microarray datasets. Machine learning techniques were subsequently employed to assess the prediction performance of the biomarkers. The biomarker set along with the Random Forest models gave the highest median area under the receiver operating characteristic curve (AUC) of 0.824 and a low interquartile range (IQR) variance of 0.036 based on a leave-one-out cross-validation. The application of the models to the external validation datasets achieved high AUC values of greater than or equal to 0.857. Enrichment analysis of the biomarkers inferred the involvement of chronic inflammatory diseases such as liver cirrhosis, fibrosis, and hepatocellular carcinoma in NGHCs. The time-invariant biomarkers provided a robust alternative for NGHC prediction.


Assuntos
Carcinógenos , Neoplasias Hepáticas , Animais , Biomarcadores , Carcinógenos/análise , Carcinógenos/toxicidade , Perfilação da Expressão Gênica , Neoplasias Hepáticas/induzido quimicamente , Toxicogenética
14.
J Environ Public Health ; 2020: 8516105, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32565841

RESUMO

Background: Community consumption of herbal plants in developing countries is a common practice, however, scarcity of information on their physiochemical composition is a major public health concern. In Uganda, Vernonia amygdalina is of interest in rural communities due to its therapeutical action on both bacterial and protozoal parasites, however no studies have been conducted to assess the heavy metal concentrations in traditional plants used in alternative medicine. The aim of the study was to establish concentrations of heavy metals in Vernonia amygdalina, model the estimated daily intake (EDI), and assess both the non-cancer-related health risk using the target hazard quotient (THQ), and the risk related to cancer through the incremental lifetime cancer risk (ILCR) for the Ugandan population. Methods: Leaves of Vernonia amygdalina were collected from 20 georeferenced villages and processed into powder in the laboratory using standard methods. These were then analyzed in the laboratory using an atomic absorption spectrometer for lead (Pb), chromium (Cr), copper (Cu), zinc (Zn), cobalt (Co), iron (Fe), cadmium (Cd), and nickel (Ni). Concentrations were compared against the World Health Organization (WHO) limits. The EDI, THQ, and ILCR were modelled and significance was measured at 95% confidence. Results: The study showed that mean ± SEM concentrations of heavy metals were highest in the order of Cr, 121.8 ± 4.291 ppm > Ni, 84.09 ± 2.725 ppm > Zn, 53.87 ± 2.277 ppm > Pb, 40.61 ± 3.891 ppm > Cu, 28.75 ± 2.202 ppm > Fe, 14.15 ± 0.7271 ppm > Co, 7.923 ± 0.7674 ppm > Cd, 0.1163 ± 0.005714 ppm. Concentrations of Pb, Cr, Zn, Co, and Ni were significantly higher than the WHO limits. The EDI was significantly higher in children than in adults, demonstrating an increased risk of toxicity in children. The THQ and ILCR were over 1000 times higher in all Ugandans, demonstrating the undesirable health risks following oral consumption of Vernonia amygdalina due to very high Cr and Ni toxicities, respectively. Conclusion: Consumption of raw Vernonia amygdalina was associated with a high carcinogenic risk, demonstrating a need to enact policies to promote physiochemical screening of herbal medicines used in developing countries against toxic compounds.


Assuntos
Exposição Dietética/análise , Contaminação de Alimentos/análise , Plantas Medicinais/química , Vernonia/química , Adulto , Carcinógenos/análise , Carcinógenos/toxicidade , Criança , Exposição Dietética/normas , Humanos , Metais Pesados/análise , Metais Pesados/toxicidade , Plantas Medicinais/toxicidade , Medição de Risco , Uganda , Vernonia/toxicidade
15.
Environ Geochem Health ; 42(11): 3675-3701, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32488799

RESUMO

Groundwater is one of the most important sources of water for drinking and cooking in rural India. A total of 382 groundwater samples were collected from 58 villages and analyzed for HMs and Sr by inductively coupled plasma mass spectrometer. The average concentrations of HMs and Sr in water was in the order of strontium (Sr) > arsenic (As) > chromium (Cr) > lead (Pb) > mercury (Hg) > cadmium (Cd). Out of 58 villages, 21, 37, 35, 35, 35 and 39 villages had Cr, As, Cd, Hg, Pb and Sr higher (WHO limit) than their respectively permissible levels. Health risk assessment of HMs and Sr for humans revealed that the non-carcinogenicity hazard quotients (HQi+d) for HMs and Sr were higher than unity for adult and children. The hazard index (HI) was 531.066 for adult and 902.926 for children. The HI > 1 was observed in 45 villages for adults and 56 villages for children. The lifetime cancer risk in adult for Asi, Asd, and Pbi in 36, 25 and 23 villages, whereas in children was 42, 20 and 22 villages, respectively. In conclusion, the health risks arising from consumption of groundwater containing HMs and Sr indicated that there is a significant carcinogenic risks for adult and children. This is the first attempt to provide information on the health risks of Sr in drinking water in India. The present findings can be useful for the development of potential strategies for risk control and management.


Assuntos
Exposição Dietética/efeitos adversos , Metais Pesados/análise , Estrôncio/análise , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Adulto , Carcinógenos/análise , Carcinógenos/toxicidade , Criança , Culinária , Exposição Dietética/análise , Água Potável/análise , Água Subterrânea/química , Humanos , Índia , Metais Pesados/toxicidade , Nível de Efeito Adverso não Observado , Medição de Risco , Estrôncio/toxicidade
16.
Toxicol Lett ; 329: 67-79, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32387197

RESUMO

This study unveiled the early cellular and molecular events induced by 1,2-dimethylhydrazine (DMH) in the colon and liver and their implications on pre- and neoplastic lesion burden in a late timepoint. Male Wistar rats received four DMH injections (40 mg/kg body weight) for 2 weeks and were sacrificed 24 h (short-term study) or 22 (medium-term study) weeks after the last DMH administration. In the short-term study, DMH led to increased leukocyte (comet assay) and colon (H2AX) genotoxicity, enhanced proliferation (Ki-67) and apoptosis (caspase-3) indexes in both liver and colon. Furthermore, the expression of mRNA (Cat, Gsta1, Gsta2, Gpx1, Gstm1, Sod1, Sod2 and Sod3) and the activity of antioxidant agents were diminished in the colon and liver of DMH-induced rats, eliciting an environment of oxidative stress featuring elevated lipid hydroperoxide levels. Apoptosis effectors were upregulated in the liver (Bax, Casp3 and Fas), and developmental genes were downregulated in both colon and liver (Foxa1, Foxa2, Smad2 and Smad4). In the medium-term study, DMH led to a high number of preneoplastic colonic aberrant crypt foci and tumors (adenomas and invasive adenocarcinomas) but few preneoplastic hepatic glutathione S-transferase (GST-P)-positive foci. Our novel gene expression data highlights overlooked mechanisms in the liver (main metabolizing organ) and colon (main target organ) on toxicity and carcinogenesis induced by repeated doses of DMH, as both organs should be considered in further interventions on the initiation stage of colon carcinogenesis.


Assuntos
1,2-Dimetilidrazina/toxicidade , Carcinógenos/toxicidade , Colo/efeitos dos fármacos , Neoplasias do Colo/induzido quimicamente , Neoplasias Hepáticas/induzido quimicamente , Fígado/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Mutagênicos/toxicidade , Ratos , Ratos Wistar
17.
Chemosphere ; 252: 126644, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32443284

RESUMO

Pendimethalin, one of the dinitroaniline group herbicides, is applied for controlling weeds in cereals, legumes and vegetable crops, and has been classified as possible human carcinogen. It is indicated that pendimethalin should arise risks of developing some cancer types; however, there is no data on the effects of pendimethalin on pancreatic cancer-induced inflammation. Injuries resulting from by acute pancreatitis attacks and inflammation are significant factors in the development of pancreatic cancer. Therefore, we investigated whether pendimethalin triggers inflammation as a mechanism of pancreatic cancer development. Parameters related to pancreatic activation, oxidative stress, and inflammation were measured in the human pancreatic (PANC-1) cell line. In the range of 0-100 µM, the levels of chymotrypsin decreased. It should be indicated that the reason for the decrease in chymotrypsin may be the high rates of cell death (20%) observed in the high concentration levels. We observed that pendimethalin significantly induced oxidative damage, while levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) did not change. The obtained results may draw attention to the usage and possible toxic effect of pendimethalin due to oxidative damage induction; however, detailed inflammation mechanisms and other cancer pathways should be investigated.


Assuntos
Compostos de Anilina/toxicidade , Carcinógenos/toxicidade , Herbicidas/toxicidade , Neoplasias Pancreáticas/induzido quimicamente , Doença Aguda , Carcinógenos/metabolismo , Herbicidas/metabolismo , Humanos , Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pâncreas/metabolismo
18.
Chemosphere ; 254: 126874, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32361543

RESUMO

Okadaic acid (OA), one of the most important phycotoxins, is widely distributed around the world, concerning diarrheic shellfish poisoning (DSP), and even colorectal cancer. Here, we found that long-term exposure of OA at a low dose (80 µg kg-1 body weight) had certain effects on colonic microbiotas and tract in rat. In the OA-exposed rat, colonic epithelium layer was damaged, and relative abundance of some microbiotas were significantly changed, especially genera in Clostridiales. However, no intestinal inflammation or significant disease was observed. Combined with the increase in relative abundance of some genera in Clostridiales induced by OA in the fermentation experiment, we proposed that OA could cause damage to the intestinal epithelium and increase the relative abundance of pathogenic bacteria, thereby increasing the probability of contact between intestinal epithelium and pathogenic bacteria and leading to an easier pathogenicity.


Assuntos
Carcinógenos/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Ácido Okadáico/toxicidade , Animais , Colo , Inflamação , Mucosa Intestinal , Intestinos , Microbiota , Ratos , Intoxicação por Frutos do Mar , Testes de Toxicidade Crônica
19.
Environ Geochem Health ; 42(9): 2895-2923, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32424788

RESUMO

The study investigated the levels of the USEPA 16 PAHs in soils collected from selected functional areas (cemetery, commercial, industrial and residential areas) of the Nigerian megacity, Lagos. The soil samples were subjected to ultrasonic-assisted extraction in a 1:1 (v/v) mixture of dichloromethane/hexane, and the PAHs in the resulting extracts were determined by gas chromatography-mass spectrometry. The Σ16 PAHs in soils of these functional areas varied between 890-4675, 485-4513, 111-15,577 and 509-2047 µg kg-1 for cemetery, industrial, commercial and residential areas, respectively. The benzo(a)pyrene carcinogenic (BaPTEQ) and mutagenic equivalency (BaPMEQ) values of PAHs in these soils spanned from 523 to 1046 and 446 to 1129 µg kg-1, respectively. The hazard index values suggested that there are adverse (non-carcinogenic) health effects for a child's exposure to PAHs in soils of commercial areas. The cancer risk values resulting from an adult's and a child's exposure to PAHs in these urban soils via dermal contact and oral ingestion surpassed the target value of 10-6 which suggested that there is a considerable cancer risk relating to human exposure to PAHs in these urban soils. An ecological risk assessment making use of soil quality guidelines and risk quotients suggested a low ecological risk to organisms in soils of these functional areas except for those from commercial areas. PAH isomeric ratios and principal component analysis indicated that PAHs in these soils arise from petrogenic inputs, such as occasional spills of liquid petroleum fuels and discharges from automobile workshops and generator houses, as well as pyrogenic processes including traffic emissions and combustion of fossil fuels and biomass.


Assuntos
Exposição Ambiental/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Poluentes do Solo/análise , Adulto , Carcinógenos/análise , Carcinógenos/toxicidade , Criança , Exposição Ambiental/análise , Monitoramento Ambiental/métodos , Humanos , Indústrias , Nigéria , Poluição por Petróleo , Medição de Risco , Solo/química , Poluentes do Solo/toxicidade
20.
Environ Toxicol ; 35(10): 1125-1136, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32449848

RESUMO

This study aimed to evaluate the in vivo anticancer effects of daucosterol which was earlier reported to possess in vitro anticancer effects. Breast tumor was induced in 30 rats using the environmental carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) while 6 control rats received olive oil (NOR). Animals with palpable tumors were randomized into five groups (n = 6) each as follows: negative control group treated with the vehicle (DMBA); positive control group treated with 5 mg/kg BW doxorubicin (DOXO + DMBA); three groups treated with daucosterol at doses of 2.5, 5, and 10 mg/kg BW (DAU + DMBA). Treatment lasted 28 days afterward, tumor (mass, volume, cancer antigen [CA] 15-3 level and histoarchitecture), hematological and toxicological parameters were examined. The tumor volume gradually increased in the DMBA group during the 28 days, with a tumor volume gain of ∼390 cm3 . Daucosterol at all doses reduced tumor volume (∼133.7 cm3 at 10 mg/kg) as well as protein, malondialdehyde (MDA), and CA 15-3 levels compared to DMBA rats. Tumor sections in daucosterol-treated rats showed a lower proliferation of mammary ducts with mild (5 and 10 mg/kg) to moderate (2.5 mg/kg) inflammatory responses. Moreover, it exhibited an antioxidant effect, evidenced by a significant and dose-dependent decreased in MDA levels, as well as an increase in catalase activity compared to the DMBA group. Daucosterol showed for the first time in vivo antitumor effects that corroborate its previous in vitro effects.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Capparaceae/química , Neoplasias Mamárias Experimentais/tratamento farmacológico , Sitosteroides/farmacologia , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/uso terapêutico , Antioxidantes/metabolismo , Carcinógenos/toxicidade , Relação Dose-Resposta a Droga , Feminino , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Estrutura Molecular , Casca de Planta/química , Ratos , Ratos Wistar , Sitosteroides/isolamento & purificação , Sitosteroides/uso terapêutico
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