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1.
Arch Environ Contam Toxicol ; 78(1): 34-45, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31781792

RESUMO

In this study, we determined the concentrations of polycyclic aromatic hydrocarbons (PAHs) in road dust from Myanmar, Japan, Taiwan, and Vietnam. PAHs were detected in urban and rural areas of Myanmar at mean concentrations of 630 ng/g dry weight and 200 ng/g dry weight, respectively. PAHs were also detected in road dust from Vietnam (mean 1700 ng/g) and Taiwan (2400 ng/g). PAH diagnostic ratios suggested that fossil fuel vehicular exhaust and biomass combustion are major sources of PAHs in road dust in Myanmar. Road dust samples from Japan, Taiwan, and Vietnam had similar PAH diagnostic ratios, implying that PAH sources are similar. We assessed the human health risks posed by PAHs in road dust using carcinogenic equivalents (CEQs) and incremental lifetime cancer risk (ILCR). Mean CEQs were decreased in the order Taiwan (173 ng/g) > Vietnam (162 ng/g for Hanoi) > Myanmar (42 and 31 ng/g for Yangon and Pathein, respectively) > Japan (30 ng/g for Kumamoto). Benz[a]pyrene, fluoranthene, and benzo[b]fluoranthene, the predominant PAHs, contributed > 70% of total CEQs. High ILCR values were found for Taiwan (5.9 × 10-4 and 9.9 × 10-4 for children and adults, respectively) and Vietnam (6.5 × 10-4 and 9.2 × 10-4 for children and adults, respectively, in Hanoi), indicating that PAHs in road dust pose cancer risks to the inhabitants of Taiwan and Hanoi. To our knowledge, this is the first report to identify PAH pollution in the environment and to evaluate the human health risks of these PAHs in Myanmar.


Assuntos
Poluentes Atmosféricos/análise , Poeira/análise , Monitoramento Ambiental/métodos , Hidrocarbonetos Policíclicos Aromáticos/análise , Adulto , Criança , Humanos , Japão , Mianmar , Neoplasias/epidemiologia , Medição de Risco , Taiwan , Emissões de Veículos/análise , Vietnã
2.
Arch Toxicol ; 91(4): 1763-1782, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27604104

RESUMO

Dioxins cause various toxic effects through the aryl hydrocarbon receptor (AHR) in vertebrates, with dramatic species and strain differences in susceptibility. Although inbred mouse strains C3H/HeJ-lpr/lpr (C3H/lpr) and MRL/MpJ-lpr/lpr (MRL/lpr) are known as dioxin-sensitive and dioxin-resistant mice, respectively, the molecular mechanism underlying this difference remains unclear. The difference in the hepatic proteome of the two mouse strains treated with vehicle or 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) was investigated by a proteomic approach of two-dimensional electrophoresis (2-DE) coupled with matrix-assisted laser desorption/ionization time-of-flight/time-of-flight tandem mass spectrometry (MALDI-TOF/TOF). To confirm the strain-difference in response to TBDD treatment, cytochrome P450 (CYP) 1A1 and 1A2 protein levels were measured in both strains. A dose of 10 µg/kg body weight of TBDD induced hepatic CYP1A1 and CYP1A2 expression in both strains, but the expression levels of both CYP1A proteins were higher in C3H/lpr mice than in MRL/lpr mice, supporting that C3H/lpr mice are more sensitive to dioxins than MRL/lpr mice. Proteins that were more induced or suppressed by TBDD treatment in C3H/lpr mice were successfully identified by 2-DE and MALDI-TOF/TOF, including proteins responsible for AHR activation through production of endogenous ligands such as aspartate aminotransferase, indolethylamine N-methyltransferase, and aldehyde dehydrogenases, as well as proteins reducing oxidative stress, such as superoxide dismutase and peroxiredoxins. Taken together, our results provide insights into the molecular mechanism underlying the high dioxin susceptibility of the C3H/lpr strain, in which AHR activation by TBDD is more prompted by the production of endogenous ligands, but the adaptation to oxidative stress is also acquired.


Assuntos
Dioxinas/toxicidade , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Receptores de Hidrocarboneto Arílico/efeitos dos fármacos , Animais , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2/metabolismo , Eletroforese em Gel Bidimensional , Feminino , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos MRL lpr , Proteoma/efeitos dos fármacos , Proteômica/métodos , Receptores de Hidrocarboneto Arílico/metabolismo , Especificidade da Espécie , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
3.
Environ Sci Technol ; 49(24): 14588-96, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26579933

RESUMO

The aim of this study was to understand the cytochrome P450 (CYP)-dependent metabolic pathway and potency of polychlorinated biphenyls (PCBs) in the Baikal seal (Pusa sibirica). In vitro metabolism of 62 PCB congener mixtures was investigated by using liver microsomes of this species. A decreased ratio of over 20% was observed for CB3, CB4, CB8, CB15, CB19, CB22, CB37, CB54, CB77, and CB105, suggesting the preferential metabolism of low-chlorinated PCBs by CYPs. The highly activated metabolic pathways in Baikal seals that were predicted from the decreased PCBs and detected hydroxylated PCBs (OH-PCBs) were CB22 to 4'OH-CB20 and CB77 to 4'OH-CB79. The total amount of OH-PCBs detected as identified and unidentified congeners accounted for only a 3.8 ± 1.7 mol % of loaded PCBs, indicating many unknown PCB metabolic pathways. To explore factors involved in CYP-dependent PCB metabolism, we examined the relationships among the structural and physicochemical properties of PCBs, the in silico PCB-CYP docking parameters, and the in vitro PCB decreased ratios by principal component analysis. Statistical analysis showed that the decreased PCB ratio was at least partly accounted for by the substituted chlorine number of PCBs and the distance from the Cl-unsubstituted carbon of docked PCBs to the heme Fe in CYP2A and 2B.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Fígado/metabolismo , Bifenilos Policlorados/farmacocinética , Focas Verdadeiras/metabolismo , Animais , Hidrocarboneto de Aril Hidroxilases/química , Hidrocarboneto de Aril Hidroxilases/genética , Hidrocarboneto de Aril Hidroxilases/metabolismo , Simulação por Computador , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/deficiência , Hidroxilação , Inativação Metabólica , Fígado/efeitos dos fármacos , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Simulação de Acoplamento Molecular , Bifenilos Policlorados/metabolismo , Análise de Componente Principal , Esteroide Hidroxilases/química , Esteroide Hidroxilases/genética , Esteroide Hidroxilases/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/farmacocinética
4.
Toxics ; 12(2)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38393207

RESUMO

Artisanal and small-scale gold mining (ASGM) poses a significant global threat due to mercury emissions and resulting health hazards. This study focuses on assessing these risks in the Abu Hamad ASGM community in Sudan. Utilizing the Mercury Analyzer 3000 (NIC), analyses of twelve soil samples (including one tailings sample) and seven water samples revealed the highest concentrations near amalgam burning locations: 34.8 mg/kg in soil (S06) and 3.26 µg/L in water (W03). Concentrations decrease with distance, with soil near burning exceeding tailings (S05 = 19.0 mg/kg). Hazard quotients indicate mercury vapor inhalation as the primary exposure route from soil, with the Hazard Index reaching 5.34 for adults and 33.4 for children close to amalgam burning sites. Water samples generally pose little risk except for W03, where children face potential danger via ingestion (HI = 1.74). These findings emphasize the urgent need for adopting retorts and eco-friendly practices to reduce mercury emissions and protect ASGM communities.

5.
Transfusion ; 52(6): 1268-75, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22188519

RESUMO

BACKGROUND: The human FUT2 gene encodes a secretor-type α(1,2)fucosyltransferase, and many population-specific polymorphisms have been reported in the coding region. STUDY DESIGN AND METHODS: Direct sequencing, real-time polymerase chain reaction, and high-resolution melt (HRM) analysis were done to detect single-nucleotide polymorphism (SNPs) and copy number variations (CNVs) in a Vietnamese population. The impacts of two novel mutations on the encoded enzyme were examined by a transient expression study. RESULTS: The major nonfunctional allele in the 294 Vietnamese was se(357,385), whereas no CNV was detected. Two novel SNPs, 818C>A (Thr273Asn) and 853G>A (Ala285Thr), distributed at low frequency, were shown to remarkably affect the enzyme activity. CONCLUSION: The allelic polymorphism of FUT2 in Vietnamese is similar to that of other East and Southeast Asian populations. This result may reflect the history and gene flow of this population. In addition, HRM analysis seems to be a simple and effective method for screening rare SNPs of FUT2 in a large number of samples. [Correction statement added after online publication 21-Dec-2011: Thr273Ala has been updated to Thr273Asn throughout.]


Assuntos
Povo Asiático/genética , Fucosiltransferases/genética , Mutação de Sentido Incorreto , Análise Mutacional de DNA , Variação Genética , Genética Populacional , Humanos , Vietnã , Galactosídeo 2-alfa-L-Fucosiltransferase
6.
Proc Natl Acad Sci U S A ; 106(26): 10859-64, 2009 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-19541612

RESUMO

Zinc (Zn) plays important roles in various biological activities but there is little available information regarding its functions in spermatogenesis. In our current study, we further examined the role of Zn during spermatogenesis in the Japanese eel (Anguilla japonica). Human CG (hCG) was injected into the animals to induce spermatogenesis, after which the concentration of Zn in the testis increased in tandem with the progression of spermatogenesis. Staining of testicular cells with a Zn-specific fluorescent probe revealed that Zn accumulates in germ cells, particularly in the mitochondria of spermatogonia and spermatozoa. Using an in vitro testicular organ culture system for the Japanese eel, production of a Zn deficiency by chelation with N,N,N',N'-tetrakis (2-pyridylemethyl)ethylenediamine (TPEN) caused apoptosis of the germ cells. However, this cell death was rescued by the addition of Zn to the cultures. Furthermore, an induced deficiency of Zn by TPEN chelation was found to inhibit the germ cell proliferation induced by 11-ketotestosterone (KT), a fish specific androgen, 17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP), the initiator of meiosis in fish, and estradiol-17beta (E2), an inducer of spermatogonial stem-cell renewal. We also investigated the effects of Zn deficiency on sperm motility and observed that TPEN treatment of eel sperm suppressed the rate and duration of their motility but that co-treatment with Zn blocked the effects of TPEN. Our present results thus suggest that Zn is an essential trace element for the maintenance of germ cells, the progression spermatogenesis, and the regulation of sperm motility.


Assuntos
Espermatogênese/fisiologia , Oligoelementos/metabolismo , Zinco/metabolismo , Anguilla/metabolismo , Anguilla/fisiologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quelantes/farmacologia , Gonadotropina Coriônica/farmacologia , Estradiol/farmacologia , Etilenodiaminas/farmacologia , Humanos , Hidroxiprogesteronas/farmacologia , Marcação In Situ das Extremidades Cortadas , Masculino , Técnicas de Cultura de Órgãos , Células de Sertoli/metabolismo , Motilidade dos Espermatozoides/efeitos dos fármacos , Motilidade dos Espermatozoides/fisiologia , Espermátides/metabolismo , Espermatócitos/metabolismo , Espermatogênese/efeitos dos fármacos , Espermatogônias/metabolismo , Espermatozoides/metabolismo , Testículo/citologia , Testículo/metabolismo , Testosterona/análogos & derivados , Testosterona/farmacologia , Fatores de Tempo , Oligoelementos/deficiência , Oligoelementos/farmacologia , Zinco/deficiência , Zinco/farmacologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-35627826

RESUMO

Mercury (Hg) is one of the most harmful metals and has been a public health concern according to the World Health Organization (WHO). Artisanal and small-scale gold mining (ASGM) is the world's fastest-growing source of Hg and can release Hg into the atmosphere, hydrosphere, and geosphere. Hg has been widely used in ASGM industries throughout Southeast Asia countries, including Cambodia, Indonesia, Laos, Malaysia, Myanmar, the Philippines, and Thailand. Here, 16 relevant studies were systematically searched by performing the PRISMA flow, combining the keywords of "Hg", "ASGM", and relevant study areas. Mercury concentrations exceeding the WHO and United States Environmental Protection Agency guideline values were reported in environmental (i.e., air, water, and soil) and biomonitoring samples (i.e., plants, fish, and human hair). ASGM-related health risks to miners and nonminers, specifically in Indonesia, the Philippines, and Myanmar, were also assessed. The findings indicated severe Hg contamination around the ASGM process, specifically the gold-amalgamation stage, was significantly high. To one point, Hg atmospheric concentrations from all observed studies was shown to be extremely high in the vicinity of gold operating areas. Attentions should be given regarding the public health concern, specifically for the vulnerable groups such as adults, pregnant women, and children who live near the ASGM activity. This review summarizes the effects of Hg in Myanmar and other Southeast Asian countries. In the future, more research and assessment will be required to investigate the current and evolving situation in ASGM communities.


Assuntos
Mercúrio , Animais , Poluição Ambiental , Feminino , Ouro , Humanos , Mercúrio/análise , Mineração , Mianmar , Gravidez , Estados Unidos
8.
Sci Total Environ ; 826: 153990, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35192832

RESUMO

Our previous studies demonstrated that prenatal bisphenol A (BPA) exposure affected the hepatic transcriptome and lipidome in rat offspring in a sex- and age-dependent manner. In this study, we investigated the effects of gestational exposure to BPA on the rat dams, after weaning period, and compared them with those of their offspring. Our results showed alterations in hepatic transcriptome related to insulin signaling, circadian rhythm, and infectious disease pathways in BPA-treated dams even 4 weeks after the exposure, whereas slight modifications on the lipid profile were found. Alterations in lipid and transcriptome profiles were more prominent in the prenatally BPA-exposed offspring at postnatal day (PND) 1 and 21 than those in the dams, suggesting that in utero exposure to BPA is more serious than exposure in the adulthood. Cryptochrome-1 (Cry1) and peroxisome proliferator-activated receptor delta (Ppard) were commonly altered in both dams and offspring. Nevertheless, the results of DIABLO (Data Integration Analysis for Biomarker discovery using Latent cOmponents), showed that multi-omics data successfully distinguished the exposed dams from the corresponding controls and their offspring with a high level of accuracy. The accuracy rates in BPA50 models (including control and 50 µg BPA/kg bw/day exposed groups) were smaller than those in BPA5000 models (control and 5000 µg BPA/kg bw/day exposed groups), suggesting dose-dependent severity in BPA effects. Palmitic acid and genes related to circadian rhythm, insulin responses, and lipid metabolism (e.g., 1-acylglycerol-3-phosphate O-acyltransferase 2 (Agpat2), B-cell CLL/lymphoma 10 (Bcl10), Cry1, Harvey rat sarcoma virus oncogene (Hras), and NLR family member X1 (Nlrx1)) were identified through DIABLO models as novel biomarkers of effects of BPA across two generations.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Transcriptoma , Adulto , Compostos Benzidrílicos/toxicidade , Feminino , Humanos , Insulina , Lipidômica , Lipídeos , Proteínas Mitocondriais , Fenóis , Gravidez
9.
Int J Mol Sci ; 12(4): 2351-82, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21731446

RESUMO

Individual variations in inorganic arsenic metabolism may influence the toxic effects. Arsenic (+3 oxidation state) methyltransferase (AS3MT) that can catalyze the transfer of a methyl group from S-adenosyl-l-methionine (AdoMet) to trivalent arsenical, may play a role in arsenic metabolism in humans. Since the genetic polymorphisms of AS3MT gene may be associated with the susceptibility to inorganic arsenic toxicity, relationships of several single nucleotide polymorphisms (SNPs) in AS3MT with inorganic arsenic metabolism have been investigated. Here, we summarize our recent findings and other previous studies on the inorganic arsenic metabolism and AS3MT genetic polymorphisms in humans. Results of genotype dependent differences in arsenic metabolism for most of SNPs in AS3MT were Inconsistent throughout the studies. Nevertheless, two SNPs, AS3MT 12390 (rs3740393) and 14458 (rs11191439) were consistently related to arsenic methylation regardless of the populations examined for the analysis. Thus, these SNPs may be useful indicators to predict the arsenic metabolism via methylation pathways.


Assuntos
Arsênio/metabolismo , Metiltransferases/genética , Polimorfismo de Nucleotídeo Único , Frequência do Gene , Humanos , Metilação , Grupos Raciais/genética , S-Adenosilmetionina/química , S-Adenosilmetionina/metabolismo
10.
Sci Total Environ ; 754: 142409, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254947

RESUMO

On April 14th and 16th, 2016, two large-scale earthquakes (Mw 6.2 and 7.0) occurred in Kumamoto, Japan. The sewer system was seriously damaged and there were concerns about groundwater pollution by sewer exfiltration. In this study, artificial sweeteners including acesulfame (ACE) in groundwater were analyzed before and after the earthquakes to evaluate sewage pollution and its temporal variation. Before the earthquakes, ACE was detected in 31 of 49 groundwater samples analyzed, indicating that wastewater may have leaked into groundwater. Groundwater was sampled from the same locations 2, 7, 12, and 30 months after the earthquakes. The detection frequency and median concentration of ACE in groundwater increased significantly 7 months after the earthquakes, from several tens to maximumly 189 times greater than the pre-earthquake concentrations. This suggests the earthquakes caused serious damage to sewer pipes and groundwater may be polluted. However, ACE concentrations drastically decreased or remained low 30 months after the earthquakes, probably due to the recovery and restoration work of sewer infrastructure. This study shows that ACE is an excellent tracer for evaluating sewer exfiltration to groundwater. In addition, it is important to obtain data on sewage tracers under normal condition as part of preparations for large-scale earthquakes.

11.
Toxicol Appl Pharmacol ; 243(3): 292-9, 2010 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-19932709

RESUMO

Human arsenic (+3 oxidation state) methyltransferase (AS3MT) is known to catalyze the methylation of arsenite. The objective of this study was to investigate the diversity of the AS3MT gene at the global level. The distribution of 18 single nucleotide polymorphisms (SNPs) in AS3MT was performed in 827 individuals from 10 populations (Japanese, Korean, Chinese, Mongolian, Tibetans, Sri Lankan Tamils, Sri Lankan Sinhalese, Nepal Tamangs, Ovambo, and Ghanaian). In the African populations, the A allele in A6144T was not observed; the allele frequencies of C35587 were much lower than those in other populations; the allele frequencies of A37616 and C37950 were relatively higher than those in other populations. Among Asian populations, Mongolians showed a different genotype distribution pattern. A lower C3963 and T6144 frequencies were observed, and, in the C37616A and T37950C polymorphism, the Mongolian population showed higher A37616 and C37950 allele frequencies than other Asian populations, similarly to the African populations. A total of 66 haplotypes were observed in the Ovambo, 48, in the Ghanaian, 99, in the Japanese, 103, in the Korean, 103, in the South Chinese, 20, in the Sri Lankan Tamil, 12, in the Sri Lankan Sinhalese, 21, in the Nepal Tamang, 50, in the Tibetan, and 45, in the Mongolian populations. The D' values between the SNP pairs were extremely high in the Sri Lankan Sinhalese population. Relatively higher D' values were observed in Mongolian and Sri Lankan Tamil populations. Network analysis showed two clusters that may have different origins, African and Asians (Chinese and/or Japanese). The present study is the first to demonstrate the existence of genetic heterogeneity in a world wide distribution of 18 SNPs in AS3MT.


Assuntos
Metiltransferases/genética , Alelos , Povo Asiático , População Negra , Primers do DNA , Interpretação Estatística de Dados , Etnicidade , Frequência do Gene , Variação Genética , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação/genética , Polimorfismo de Nucleotídeo Único/genética
12.
Toxicol Appl Pharmacol ; 242(3): 352-62, 2010 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-19914269

RESUMO

To elucidate the role of genetic factors in arsenic metabolism, we investigated associations of genetic polymorphisms in the members of glutathione S-transferase (GST) superfamily with the arsenic concentrations in hair and urine, and urinary arsenic profile in residents in the Red River Delta, Vietnam. Genotyping was conducted for GST omega1 (GSTO1) Ala140Asp, Glu155del, Glu208Lys, Thr217Asn, and Ala236Val, GST omega2 (GSTO2) Asn142Asp, GST pi1 (GSTP1) Ile105Val, GST mu1 (GSTM1) wild/null, and GST theta1 (GSTT1) wild/null. There were no mutation alleles for GSTO1 Glu208Lys, Thr217Asn, and Ala236Val in this population. GSTO1 Glu155del hetero type showed higher urinary concentration of As(V) than the wild homo type. Higher percentage of DMA(V) in urine of GSTM1 wild type was observed compared with that of the null type. Strong correlations between GSTP1 Ile105Val and arsenic exposure level and profile were observed in this study. Especially, heterozygote of GSTP1 Ile105Val had a higher metabolic capacity from inorganic arsenic to monomethyl arsenic, while the opposite trend was observed for ability of metabolism from As(V) to As(III). Furthermore, other factors including sex, age, body mass index, arsenic level in drinking water, and genotypes of As (+3 oxidation state) methyltransferase (AS3MT) were also significantly co-associated with arsenic level and profile in the Vietnamese. To our knowledge, this is the first study indicating the associations of genetic factors of GST superfamily with arsenic metabolism in a Vietnamese population.


Assuntos
Arsênio/metabolismo , Glutationa Transferase/genética , Metiltransferases/genética , Poluentes Químicos da Água/metabolismo , Adolescente , Adulto , Fatores Etários , Idoso , Arsênio/urina , Índice de Massa Corporal , Criança , Feminino , Genótipo , Cabelo/química , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Rios/química , Fatores Sexuais , Vietnã , Poluentes Químicos da Água/urina , Adulto Jovem
13.
Rev Environ Health ; 25(3): 193-220, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21038756

RESUMO

In this review, we summarize the current knowledge on exposure, metabolism, and health effects of arsenic (As) in residents from As-contaminated groundwater areas of Vietnam and Cambodia based on our findings from 2000 and other studies. The health effects of As in humans include severe gastrointestinal disorders, hepatic and renal failure, cardiovascular disturbances, skin pigmentation, hyperkeratosis, and cancers in the lung, bladder, liver, kidney, and skin. Arsenic contamination in groundwater is widely present at Vietnam and Cambodia and the highest As levels are frequently found in groundwater from Cambodia. Sand filter system can reduce As concentration in raw groundwater. The results of hair and urine analyses indicate that residents from these As-contaminated areas are exposed to As. In general, sex, age, body mass index, and As exposure level are significantly associated with As metabolism. Genetic polymorphisms in arsenic (+III) methyltransferase and glutathione-S-transferase isoforms may be influenced As metabolism and accumulation in a Vietnamese population. It is suggested oxidative DNA damage is caused by exposure to As in groundwater from residents in Cambodia. An epidemiologic study on an association of As exposure with human health effects is required in these areas.


Assuntos
Intoxicação por Arsênico/etiologia , Arsênio/efeitos adversos , Exposição Ambiental/efeitos adversos , Poluentes Químicos da Água/efeitos adversos , Arsênio/análise , Arsênio/metabolismo , Intoxicação por Arsênico/epidemiologia , Intoxicação por Arsênico/genética , Intoxicação por Arsênico/prevenção & controle , Camboja/epidemiologia , Dano ao DNA , Exposição Ambiental/prevenção & controle , Contaminação de Alimentos , Humanos , Oryza , Polimorfismo Genético , Vietnã/epidemiologia , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/metabolismo
14.
Sci Total Environ ; 720: 137568, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32145629

RESUMO

Developmental exposure to bisphenol A (BPA) is associated with liver dysfunction and diseases in adulthood. The aims of this study were to assess the effects of prenatal BPA exposure on the hepatic transcriptome and proteome in female and male offspring and to understand adverse outcome pathways (AOPs) to observed phenotypic effects. Pregnant Wistar rats were exposed to 50 or 5000 µg BPA/kg bw/day, or 17ß-estradiol (E2, 50 µg/kg bw/day) from embryonic day 3 to 18. The liver transcriptome and proteome profiles were analyzed in the newborn (postnatal day 1; PND1) and weaning (PND21) rat offspring. Based on the differentially expressed genes/proteins derived from transcriptome and proteome profiles, we performed pathway, transcription factor, and disease enrichment analyses. A principal component analysis of transcriptome data demonstrated that prenatal BPA exposure caused masculinization of the hepatic transcriptome in females. Both of transcriptomic and proteomic data showed that prenatal BPA exposure led to the disruption of cell cycle, lipid homeostasis, and hormone balance in offspring. Most of the effects at the transcript level were extended from newborn to weaning in males, but were moderated until weaning in females. The alterations at the transcript and protein levels were accordant with the observation of increases in body weight and anogenital distance and changes in hepatosomatic index in the offspring. Collectively, we constructed AOPs with evidence of sex- and age-specific actions of prenatal BPA exposure in the offspring.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Proteoma , Transcriptoma , Animais , Compostos Benzidrílicos , Feminino , Fígado , Masculino , Fenóis , Gravidez , Proteômica , Ratos , Ratos Wistar
15.
Toxicol Appl Pharmacol ; 234(1): 41-6, 2009 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-18976679

RESUMO

Human arsenic (+3 oxidation state) methyltransferase (AS3MT) is known to catalyze the methylation of arsenite, and intronic single-nucleotide polymorphisms (SNPs: G7395A, G12390C, T14215C, T35587C, and G35991A) in the AS3MT gene were shown to be related to inter-individual variation in the arsenic metabolism. In the present study, the genotyping for these SNPs was developed using the polymerase chain reaction and restriction fragment length polymorphism technique. Applying this method, the genotype distribution among the Ovambo, Turkish, Mongolian, Korean, and Japanese populations was investigated, and our results were compared with those from other studies. G7395, G12390, T35587, and A35991 were predominant among the five populations in our study. However, a previous study in Argentina, C12390 and G35991 showed the highest allele frequency among the eight populations studied in other studies. The dominant allele of T14215C differed among populations: the T14215 allele was predominant in Argentina, the allele frequency of C14215 was higher than that of T14215 among Turks, Mongolians, Europeans, and American ancestry. In Korea and Japan, similar allele frequencies were observed in T14215 and C14215. Higher allele frequencies were observed in haplotype G7395/G12390/C14215/T35587 with frequencies of 0.40 (Turks), 0.28 (Mongolians), and 0.23 (Koreans). On the other hand, the allele frequency for G7395/G14215/T35587/A35991 was the highest among the Ovambos (0.32), and the frequency for G7395/G12390/C35587/G35991 was the highest among the Japanese (0.27). It is noteworthy that the Japanese haplotype differs from that of the Koreans and Mongolians, which indicates the importance of investigating other intronic polymorphisms in AS3MT, especially in Asians.


Assuntos
Arsênio/metabolismo , Metiltransferases/genética , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Alelos , Povo Asiático/genética , População Negra/genética , Frequência do Gene , Haplótipos , Humanos , Íntrons/genética , Japão , Coreia (Geográfico) , Mongólia , Namíbia , Turquia , Poluentes Químicos da Água/metabolismo , População Branca/genética
16.
Toxicol Appl Pharmacol ; 236(2): 131-41, 2009 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-19371612

RESUMO

To elucidate the role of genetic factors in arsenic (As) metabolism, we studied associations of single nucleotide polymorphisms (SNPs) in As (+3 oxidation state) methyltransferase (AS3MT) with the As concentrations in hair and urine, and urinary As profile in residents in the Red River Delta, Vietnam. Concentrations of total As in groundwater were 0.7-502 mug/l. Total As levels in groundwater drastically decreased by using sand filter, indicating that the filter could be effective to remove As from raw groundwater. Concentrations of inorganic As (IAs) in urine and total As in hair of males were higher than those of females. A significant positive correlation between monomethylarsonic acid (MMA)/IAs and age in females indicates that older females have higher methylation capacity from IAs to MMA. Body mass index negatively correlated with urinary As concentrations in males. Homozygote for SNPs 4602AA, 35991GG, and 37853GG, which showed strong linkage disequilibrium (LD), had higher percentage (%) of dimethylarsinic acid (DMA) in urine. SNPs 4740 and 12590 had strong LD and associated with urinary %DMA. Although SNPs 6144, 12390, 14215, and 35587 comprised LD cluster, homozygotes in SNPs 12390GG and 35587CC had lower DMA/MMA in urine, suggesting low methylation capacity from MMA to DMA in homo types for these SNPs. SNPs 5913 and 8973 correlated with %MMA and %DMA, respectively. Heterozygote for SNP 14458TC had higher MMA/IAs in urine than TT homozygote, indicating that the heterozygote may have stronger methylation ability of IAs. To our knowledge, this is the first study on the association of genetic factors with As metabolism in Vietnamese.


Assuntos
Arsênio/metabolismo , Metiltransferases/genética , Polimorfismo de Nucleotídeo Único , Poluentes Químicos da Água/metabolismo , Adolescente , Adulto , Idoso , Envelhecimento , Arsênio/toxicidade , Arsênio/urina , Criança , Feminino , Filtração , Regulação da Expressão Gênica/fisiologia , Cabelo/química , Humanos , Masculino , Pessoa de Meia-Idade , Rios/química , Caracteres Sexuais , Dióxido de Silício , Vietnã , Poluentes Químicos da Água/toxicidade , Abastecimento de Água/análise , Adulto Jovem
17.
Clin Exp Pharmacol Physiol ; 36(3): 283-6, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18986335

RESUMO

1. Glutathione S-transferase class omega (GSTO) 1 and 2 are members of the glutathione-S-transferase family, which uses glutathione in the process of the biotransformation of drugs, xenobiotics and oxidative stress. Associations with the age-at-onset of Alzheimer's and Parkinson's diseases have been shown in the genetic polymorphism of GSTO1 and GSTO2. 2. In the present study, the frequencies of GSTO1*A140D and GSTO2*N142D in Ovambos (n = 163), Turks (n = 194), Mongolians (n = 243) and Japanese (n = 102) were investigated and compared with findings from other studies. Detection of these single nucleotide polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. 3. The allele frequencies of these polymorphisms in Ovambos, Turks, Mongolians and Japanese were 0.040, 0.085, 0.128 and 0.108, respectively, for GSTO1*A140D and 0.583, 0.219, 0.173 and 0.216, respectively, for GSTO2*N142D. Ovambos showed the lowest allele frequency of GSTO1*A140D. Conversely, Africans, including Ovambos, showed higher allele frequencies of GSTO2*N142D than Caucasians and Asians. 4. The existence of a certain genetic heterogeneity in the worldwide distribution of these two polymorphisms is revealed in the present study.


Assuntos
Genética Populacional , Glutationa Transferase/genética , Polimorfismo de Nucleotídeo Único , Povo Asiático/genética , População Negra/genética , Frequência do Gene , Humanos , Japão , Mongólia , Namíbia , Turquia , População Branca/genética
18.
Rev Environ Contam Toxicol ; 195: 31-69, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18418953

RESUMO

Although there have been numerous studies on arsenic in low-trophic-level marine organisms, few studies exist on arsenic in marine mammals, seabirds, and sea turtles. Studies on arsenic species and their concentrations in these animals are needed to evaluate their possible health effects and to deepen our understanding of how arsenic behaves and cycles in marine ecosystems. Most arsenic in the livers of marine mammals, seabirds, and sea turtles is AB, but this form is absent or occurs at surprisingly low levels in the dugong. Although arsenic levels were low in marine mammals, some seabirds, and some sea turtles, the black-footed albatross and hawksbill and loggerhead turtles showed high concentrations, comparable to those in marine organisms at low trophic levels. Hence, these animals may have a specific mechanism for accumulating arsenic. Osmoregulation in these animals may play a role in the high accumulation of AB. Highly toxic inorganic arsenic is found in some seabirds and sea turtles, and some evidence suggests it may act as an endocrine disruptor, requiring new and more detailed studies for confirmation. Furthermore, DMA(V) and arsenosugars, which are commonly found in marine animals and marine algae, respectively, might pose risks to highly exposed animals because of their tendency to form reactive oxygen species. In marine mammals, arsenic is thought to be mainly stored in blubber as lipid-soluble arsenicals. Because marine mammals occupy the top levels of their food chain, work to characterize the lipid-soluble arsenicals and how they cycle in marine ecosystems is needed. These lipid-soluble arsenicals have DMA precursors, the exact structures of which remain to be determined. Because many more arsenicals are assumed to be present in the marine environment, further advances in analytical capabilities can and will provide useful future information on the transformation and cycling of arsenic in the marine environment.


Assuntos
Arsênio , Arsenicais/metabolismo , Poluentes Químicos da Água/farmacocinética , Animais , Arsênio/análise , Arsênio/classificação , Arsênio/farmacocinética , Aves , Cetáceos , Comportamento Alimentar , Feminino , Masculino , Distribuição Tecidual , Tartarugas , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
19.
Environ Pollut ; 153(1): 127-36, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-17728031

RESUMO

Concentrations of total arsenic (As) and individual compounds were determined in green and hawksbill turtles from Ishigaki Island, Japan. In both species, total As concentrations were highest in muscle among the tissues. Arsenobetaine was a major compound in most tissues of both turtles. High concentrations of trimethylarsine oxide were detected in hawksbill turtles. A significant negative correlation between standard carapace length (SCL), an indicator of age, and total As levels in green turtles was found. In contrast, the levels increased with SCL of hawksbill turtles. Shifts in feeding habitats with growth may account for such a growth-dependent accumulation of As. Although concentrations of As in marine sponges, the major food of hawksbill turtles are not high compared to those in algae eaten by green turtles, As concentrations in hawksbill turtles were higher than those in green turtles, indicating that hawksbill turtles may have a specific accumulation mechanism for As.


Assuntos
Arsenicais/análise , Tartarugas/metabolismo , Poluentes Químicos da Água/análise , Animais , Arsênio/análise , Arsênio/farmacocinética , Arsenicais/farmacocinética , Ecologia/métodos , Cadeia Alimentar , Humanos , Japão , Masculino , Fatores Sexuais , Especificidade da Espécie , Distribuição Tecidual , Tartarugas/anatomia & histologia , Tartarugas/crescimento & desenvolvimento , Poluentes Químicos da Água/farmacocinética
20.
Mar Pollut Bull ; 57(6-12): 782-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18291422

RESUMO

Total arsenic (As) and its compounds were determined in liver, kidney, muscle, and stomach contents of green turtles (Chelonia mydas). Total As concentrations in the muscle were higher than those in the kidney and liver. Arsenobetaine (AB) was the predominant compound in all the three tissues and its levels were positively correlated with total As concentrations. This indicates that AB greatly contributes to As accumulation in green turtles. Higher concentrations of remaining As in the sample after extraction were detected in the liver, implying that lipid-soluble or protein bound As compounds accumulate in the liver of green turtles. Total As levels in tissues showed significant negative correlations with standard carapace length. The size-dependence of As accumulation in green turtles may be related to their feeding habit, shifting from carnivore to herbivore at different growth stages. Concentrations of AB and dimethylarsinic acid (DMA) were low in the stomach contents but high in the tissues, implying bioaccumulation of these arsenicals in green turtles.


Assuntos
Arsênio/metabolismo , Arsenicais/metabolismo , Tartarugas/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Tamanho Corporal , Feminino , Geografia , Masculino , Distribuição Tecidual
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