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Epigenomics ; 12(3): 221-233, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31961222


Aim: We aimed to identify differential methylation of genes that could illuminate the biological mechanisms of chromium (VI) toxicity in this exposure-control study. Materials & methods: DNA methylation was measured in blood samples collected from electroplating workers and controls using a combination of Infinium Methylation450K Chip and targeted-bisulfite sequencing. QuantiGene assay was used to detect the mRNA expression of differentially methylated genes. Inductively coupled plasma-mass spectrometry was used to quantify metals in blood and urine samples. The cytosine-phosphate-guanine sites methylation and gene expression were confirmed in a human lymphoblastoid cell line. Results & conclusion: A total of 131 differentially methylated cytosine-phosphate-guanine sites were found between exposures and controls. DNA methylation of SEMA4B may serve as a potential biomarker for chromium (VI) exposure.

Biomarcadores , Carcinógenos Ambientais/efeitos adversos , Cromo/efeitos adversos , Metilação de DNA , Epigênese Genética/efeitos dos fármacos , Epigenômica , Exposição Ocupacional/efeitos adversos , Epigenômica/métodos , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Transcriptoma
J Expo Sci Environ Epidemiol ; 28(6): 589-598, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29463903


Acrylamide (AA), a probable human carcinogen, is a widely-used industrial chemical but is also present in tobacco smoke and carbohydrate-rich foods processed at high temperatures. AA is metabolized to glycidamide (GA) to cause the formation of DNA adducts. N7-(2-carbamoyl-2-hydroxyethyl) guanine (N7-GAG), the most abundant DNA adduct induced by GA, was recently detected in urine of smokers and non-smokers. In this study, we assessed the variability of AA exposure and biomarkers of AA exposure in urine samples repeatedly collected from AA-exposed workers and explored the half-life of N7-GAG. A total of 8 AA-exposed workers and 36 non-exposed workers were recruited. Pre-shift and post-shift urine samples were collected from the exposed group in parallel with personal sampling for eight consecutive days and from the control group on day 1 of the study. Urinary N7-GAG and the mercapturic acids of AA and GA, namely N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-(R,S)-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) were analyzed using on-line solid phase extraction-liquid chromatography-electrospray ionization/tandem mass spectrometry methods. We found that N7-GAG levels in urine were significantly higher in exposed workers than in controls and that N7-GAG level correlated positively with AAMA and GAMA levels. Results from this study showed that AAMA and GAMA possibly remain the more preferred biomarkers of AA exposure and that N7-GAG levels could be elevated by occupational exposures to AA and serve as a biomarker of AA-induced genotoxicity for epidemiological studies.

Acrilamida/urina , Biomarcadores/urina , Guanina/análogos & derivados , Guanina/urina , Exposição Ocupacional/análise , Adulto , Análise de Variância , Cromatografia Líquida/métodos , Cromatografia Líquida/normas , Monitoramento Ambiental/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Espectrometria de Massas em Tandem/métodos , Espectrometria de Massas em Tandem/normas
Sci Total Environ ; 607-608: 1126-1135, 2017 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-28724251


Prenatal exposure to phenols, phthalates (PAEs), and organophosphate (OP) pesticides may increase the risk of abnormal birth outcomes. However, many previous studies have examined exposure to a limited number of chemical classes or exposure profiles limited to a specific stage of pregnancy. This study aims to characterize the concurrent exposure scenario throughout pregnancy by simultaneously monitoring internal doses of several endocrine-disrupting compounds (EDCs), including 2 phenols (nonylphenol (NP) and bisphenol A (BPA)), 9 PAEs, and 6 OP pesticide metabolites and to assess the relationships between concurrent exposure to EDCs and infant birth weight, length, and head and chest circumference. One hundred and sixty two women provided three spot urine samples at approximately 11 and 26weeks gestation and at delivery. We applied multivariable linear regression and ridge regression models to estimate the effects of separate and correlated exposures. Multivariable linear regression models revealed that women with short birth-length infants had significantly higher urinary second-trimester NP levels (50th percentile, 5.03µg/g creatinine) (ß=-0.47cm; 95% CI=-0.93 to -0.01). Similarly significant relationships were observed between second-trimester mono-methyl phthalate (MMP) exposure and short birth length, second-trimester ΣPAEs and short birth length, second-trimester ΣPAEs exposure and reduced head and chest circumference, second-trimester diethylphosphate (DEP) exposure and reduced birth weight and length, and second-trimester ΣDEPs exposure and short birth length. Women with urinary BPA above the 75th percentile or ΣPAEs levels above the 50th percentile in the third trimester had infants with significantly reduced head circumference. These observations suggest that the second trimester may be the critical stage of susceptibility for fetal development. In ridge regression models, for which women with fewer measures for exposure to NP, BPA, MMP, ΣPAEs, DEP and ΣDEPs simultaneously were available, no relationships were found with infant size at birth. Additional studies with larger sample sizes are warranted.

Compostos Benzidrílicos/efeitos adversos , Exposição Materna/efeitos adversos , Organofosfatos/efeitos adversos , Fenóis/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Peso ao Nascer , Estatura , Estudos de Coortes , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Humanos , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Taiwan
Environ Sci Technol ; 51(11): 6422-6429, 2017 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-28490175


Prenatal exposure to nonylphenol (NP) and/or bisphenol A (BPA) has been reported to be associated with adverse birth outcomes; however, the underlying mechanisms remain unclear. The primary mechanism is endocrine disruption of the binding affinity for the estrogen receptor, but oxidative stress and inflammation might also play a contributory role. We aimed to investigate urinary NP and BPA levels in relation to biomarkers of oxidative/nitrative stress and inflammation and to explore whether changes in oxidative/nitrative stress are a function of prenatal exposure to NP/BPA and inflammation in 241 mother-fetus pairs. Third-trimester urinary biomarkers of oxidative/nitrative stress were simultaneously measured, including products of oxidatively and nitratively damaged DNA (8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-nitroguanine (8-NO2Gua)) as well as products of lipid peroxidation (8-iso-prostaglandin F2α (8-isoPF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)). The antioxidant glutathione peroxidase (GPx) and inflammation biomarkers, including C-reactive protein (CRP) and a panel of cytokines (interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)), were analyzed in maternal and umbilical cord plasma samples. In adjusted models, we observed significant positive associations between NP exposure and 8-OHdG and 8-NO2Gua levels, between BPA and 8-isoPF2α levels, and between maternal CRP levels and HNE-MA levels. Additionally, BPA and TNF-α levels in cord blood were inversely associated with maternal and GPx levels in cord blood as well as maternal TNF-α levels were inversely associated with maternal GPx levels. These results support a role for exposure to NP and BPA and possibly inflammation in increasing oxidative/nitrative stress and decreasing antioxidant activity during pregnancy.

Compostos Benzidrílicos/toxicidade , Dano ao DNA , Inflamação , Estresse Oxidativo , Fenóis/toxicidade , Adulto , Biomarcadores , Estudos de Coortes , Feminino , Sangue Fetal , Humanos , Exposição Materna , Gravidez , Fator de Necrose Tumoral alfa/sangue
Sci Total Environ ; 443: 812-20, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23246661


OBJECTIVE: This study aimed to associate hospital admissions of kidney diseases with extreme temperature and prolonged heat/cold events in 7 regions of Taiwan. METHODS: Age-specific (<65 years, 65+years and all ages) hospital admission records of nephritis, nephrotic syndrome, or nephrosis, in the form of electronic insurance reimbursement claims, were retrieved from Taiwan's National Health Insurance Research Database during the period of 2000-2008. The area-age-specific relative risk (RR) accounting for 8 days of lag for temperature on hospital admissions of kidney diseases were estimated using distributed lag non-linear models with the Poisson distribution controlling for extreme temperature events, levels of air pollutants (PM(10), O(3), and NO(2)) and potential confounders. RESULTS: We observed a V or J-shape association between daily average temperatures and the RR estimates for hospital admissions of kidney diseases in Taiwan. The lowest risk for hospital admissions of kidney diseases was found at around 25 °C, and risk increased as temperatures deviated from 25 °C. The pooled cumulative 8-day RR for all ages of population of the 7 study areas were 1.10 (95% confidence interval (CI): 1.01, 1.19) at 18 °C and 1.45 (95% CI: 1.27, 1.64) at 30 °C. High temperature has more profound influence on hospital admission of kidney diseases than low temperature. Temperature risks for hospital admissions were similar between younger (<65 years) and elderly (65+years) population. This study observed no significant effects of prolonged heat extremes on hospital admissions of kidney diseases. CONCLUSIONS: The heat effect for kidney morbidities leading to hospital admission was more significant than that of the cold temperature. This study did not find the age-dependent relative risks for temperature associating with hospital admissions of kidney diseases.

Clima , Hospitalização , Nefropatias/fisiopatologia , Admissão do Paciente , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taiwan