Prenatal arsenic exposure and the epigenome: altered microRNAs associated with innate and adaptive immune signaling in newborn cord blood.

Science.gov (United States)

Rager, Julia E; Bailey, Kathryn A; Smeester, Lisa; Miller, Sloane K; Parker, Joel S; Laine, Jessica E; Drobná, Zuzana; Currier, Jenna; Douillet, Christelle; Olshan, Andrew F; Rubio-Andrade, Marisela; Stýblo, Miroslav; García-Vargas, Gonzalo; Fry, Rebecca C

2014-04-01

The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In this study, we examined a subset (n = 40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 µg/L (mean = 51.7 µg/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 µg/L (mean = 64.5 µg/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations. Copyright © 2013 Wiley Periodicals, Inc.

In-utero cigarette smoke exposure and the risk of earlier menopause

NARCIS (Netherlands)

Honorato, Talita C; Haadsma, Maaike L; Land, Jolande A; Boezen, Marike H; Hoek, Annemieke; Groen, Henk

2018-01-01

OBJECTIVE: Cigarette smoking is a risk factor for earlier menopause. Animal studies show that in-utero smoke exposure is toxic to developing ovaries. Our aim was to evaluate whether in-utero smoke exposed women reach menopause earlier compared with nonexposed women. METHODS: This is a cohort study

Expression of the sFLT1 gene in cord blood cells is associated to maternal arsenic exposure and decreased birth weight.

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Sylvie Remy

Full Text Available There is increasing epidemiologic evidence that arsenic exposure in utero is associated with adverse pregnancy outcomes and may contribute to long-term health effects. These effects may occur at low environmental exposures but the underlying molecular mechanism is not clear. We collected cord blood samples of 183 newborns to identify associations between arsenic levels and birth anthropometric parameters in an area with very low arsenic exposure. Our core research aim was to screen for transcriptional marks that mechanistically explain these associations. Multiple regression analyses showed that birth weight decreased with 47 g (95% CI: 16-78 g for an interquartile range increase of 0.99 μg/L arsenic. The model was adjusted for child's sex, maternal smoking during pregnancy, gestational age, and parity. Higher arsenic concentrations and reduced birth weight were positively associated with changes in expression of the sFLT1 (soluble fms-like tyrosine kinase-1 gene in cord blood cells in girls. The protein product of sFLT1 is a scavenger of vascular endothelial growth factor (VEGF in the extracellular environment and plays a key role in the inhibition of placental angiogenesis. In terms of fetal development, inhibition of placental angiogenesis leads to impaired nutrition and hence to growth retardation. Various genes related to DNA methylation and oxidative stress showed also changed expression in relation to arsenic exposure but were not related to birth outcome parameters. In conclusion, this study suggests that increased expression of sFLT1 is an intermediate marker that points to placental angiogenesis as a pathway linking prenatal arsenic exposure to reduced birth weight.

Alcohol Exposure In Utero and Child Academic Achievement

OpenAIRE

Stephanie von Hinke Kessler Scholder; George L. Wehby; Sarah Lewis; Luisa Zuccolo

2014-01-01

We examine the effect of alcohol exposure in utero on child academic achievement. As well as studying the effect of any alcohol exposure, we investigate the effect of the dose, pattern, and duration of exposure. We use a genetic variant in the maternal alcohol-metabolism gene ADH1B as an instrument for alcohol exposure, whilst controlling for the child's genotype on the same variant. We show that the instrument is unrelated to an extensive range of maternal and paternal characteristics and be...

Maternal Arsenic Exposure, Arsenic Methylation Efficiency, and Birth Outcomes in the Biomarkers of Exposure to ARsenic (BEAR) Pregnancy Cohort in Mexico

Science.gov (United States)

Laine, Jessica E.; Bailey, Kathryn A.; Rubio-Andrade, Marisela; Olshan, Andrew F.; Smeester, Lisa; Drobná, Zuzana; Herring, Amy H.; Stýblo, Miroslav; García-Vargas, Gonzalo G.

2014-01-01

Background: Exposure to inorganic arsenic (iAs) from drinking water is a global public health problem, yet much remains unknown about the extent of exposure in susceptible populations. Objectives: We aimed to establish the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort in Gómez Palacio, Mexico, to better understand the effects of iAs exposure on pregnant women and their children. Methods: Two hundred pregnant women were recruited for this study. Concentrations of iAs in drinking water (DW-iAs) and maternal urinary concentrations of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) were determined. Birth outcomes were analyzed for their relationship to DW-iAs and to the concentrations and proportions of maternal urinary arsenicals. Results: DW-iAs for the study subjects ranged from iAs that exceeded the World Health Organization’s recommended guideline of 10 μg As/L. DW-iAs was significantly associated with the sum of the urinary arsenicals (U-tAs). Maternal urinary concentrations of MMAs were negatively associated with newborn birth weight and gestational age. Maternal urinary concentrations of iAs were associated with lower mean gestational age and newborn length. Conclusions: Biomonitoring results demonstrate that pregnant women in Gómez Palacio are exposed to potentially harmful levels of DW-iAs. The data support a relationship between iAs metabolism in pregnant women and adverse birth outcomes. The results underscore the risks associated with iAs exposure in vulnerable populations. Citation: Laine JE, Bailey KA, Rubio-Andrade M, Olshan AF, Smeester L, Drobná Z, Herring AH, Stýblo M, García-Vargas GG, Fry RC. 2015. Maternal arsenic exposure, arsenic methylation efficiency, and birth outcomes in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Mexico. Environ Health Perspect 123:186–192; http://dx.doi.org/10.1289/ehp.1307476 PMID:25325819

Role of complex organic arsenicals in food in aggregate exposure to arsenic

Science.gov (United States)

For much of the world’s population, food is the major source of exposure to arsenic. Exposure to this non-essential metalloid at relatively low levels has been linked to a wide range of adverse health effects. Thus, evaluating foods as sources of exposure to arsenic is important ...

Biological monitoring of arsenic exposure of gallium arsenide- and inorganic arsenic-exposed workers by determination of inorganic arsenic and its metabolites in urine and hair

Energy Technology Data Exchange (ETDEWEB)

Yamauchi, H.; Takahashi, K.; Mashiko, M.; Yamamura, Y. (St. Marianna Univ. School of Medicine, Kawasaki (Japan))

1989-11-01

In an attempt to establish a method for biological monitoring of inorganic arsenic exposure, the chemical species of arsenic were measured in the urine and hair of gallium arsenide (GaAs) plant and copper smelter workers. Determination of urinary inorganic arsenic concentration proved sensitive enough to monitor the low-level inorganic arsenic exposure of the GaAs plant workers. The urinary inorganic arsenic concentration in the copper smelter workers was far higher than that of a control group and was associated with high urinary concentrations of the inorganic arsenic metabolites, methylarsonic acid (MAA) and dimethylarsinic acid (DMAA). The results established a method for exposure level-dependent biological monitoring of inorganic arsenic exposure. Low-level exposures could be monitored only by determining urinary inorganic arsenic concentration. High-level exposures clearly produced an increased urinary inorganic arsenic concentration, with an increased sum of urinary concentrations of inorganic arsenic and its metabolites (inorganic arsenic + MAA + DMAA). The determination of urinary arsenobetaine proved to determine specifically the seafood-derived arsenic, allowing this arsenic to be distinguished clearly from the arsenic from occupational exposure. Monitoring arsenic exposure by determining the arsenic in the hair appeared to be of value only when used for environmental monitoring of arsenic contamination rather than for biological monitoring.

Mthfr gene ablation enhances susceptibility to arsenic prenatal toxicity

International Nuclear Information System (INIS)

Wlodarczyk, Bogdan J.; Zhu, Huiping; Finnell, Richard H.

2014-01-01

Background: In utero exposure to arsenic is known to adversely affect reproductive outcomes. Evidence of arsenic teratogenicity varies widely and depends on individual genotypic differences in sensitivity to As. In this study, we investigated the potential interaction between 5,10-methylenetetrahydrofolate reductase (Mthfr) genotype and arsenic embryotoxicity using the Mthfr knockout mouse model. Methods: Pregnant dams were treated with sodium arsenate, and reproductive outcomes including: implantation, resorption, congenital malformation and fetal birth weight were recorded at E18.5. Results: When the dams in Mthfr +/− × Mthfr +/− matings were treated with 7.2 mg/kg As, the resorption rate increased to 43.4%, from a background frequency of 7.2%. The As treatment also induced external malformations (40.9%) and significantly lowered the average fetal birth weight among fetuses, without any obvious toxic effect on the dam. When comparing the pregnancy outcomes resulting from different mating scenarios (Mthfr +/+ × Mthfr +/− , Mthfr +/− × Mthfr +/− and Mthfr −/− × Mthfr+/− ) and arsenic exposure; the resorption rate showed a linear relationship with the number of null alleles (0, 1 or 2) in the Mthfr dams. Fetuses from nullizygous dams had the highest rate of external malformations (43%) and lowest average birth weight. When comparing the outcomes of reciprocal matings (nullizygote × wild-type versus wild-type × nullizygote) after As treatment, the null dams showed significantly higher rates of resorptions and malformations, along with lower fetal birth weights. Conclusions: Maternal genotype contributes to the sensitivity of As embryotoxicity in the Mthfr mouse model. The fetal genotype, however, does not appear to affect the reproductive outcome after in utero As exposure. - Highlights: • An interaction between Mthfr genotype and arsenic embryotoxicity is presented. • Maternal Mthfr genotype contributes to the sensitivity of As

Assessing the impact of in-utero exposures: potential effects of paracetamol on male reproductive development.

Science.gov (United States)

Kilcoyne, Karen R; Mitchell, Rod T

2017-12-01

Human male reproductive disorders (cryptorchidism, hypospadias, testicular cancer and low sperm counts) are common and some may be increasing in incidence worldwide. These associated disorders can arise from subnormal testosterone production during fetal life. This has resulted in a focus on in-utero environmental influences that may result in reproductive effects on the offspring in later life. Over recent years, there has been a dramatic increase in the scientific literature describing associations between in-utero environmental exposures (eg, industrial chemicals and pharmaceuticals) and subsequent reproductive outcomes in male offspring. This includes studies investigating a potential role for in-utero analgesic exposure(s) on the fetal testis; however, providing definitive evidence of such effects presents numerous challenges. In this review, we describe an approach to assessing the potential clinical relevance of in-utero (and postnatal) environmental exposures on subsequent male reproductive function using exposure to the analgesic paracetamol as an example. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Correlation of arsenic exposure through drinking groundwater and urinary arsenic excretion among adults in Pakistan.

Science.gov (United States)

Ahmed, Mubashir; Fatmi, Zafar; Ali, Arif

2014-01-01

Long-term exposure to arsenic has been associated with manifestation of skin lesions (melanosis/keratosis) and increased risk of internal cancers (lung/bladder). The objective of the study described here was to determine the relationship between exposure of arsenic through drinking groundwater and urinary arsenic excretion among adults > or =15 years of age living in Khairpur district, Pakistan. Total arsenic was determined in drinking groundwater and in spot urine samples of 465 randomly selected individuals through hydride generation-atomic absorption spectrometry. Spearman's rank correlation coefficient was calculated between arsenic in drinking groundwater and arsenic excreted in urine. The median arsenic concentration in drinking water was 2.1 microg/L (range: 0.1-350), and in urine was 28.5 microg/L (range: 0.1-848). Positive correlation was found between total arsenic in drinking water and in urine (r = .52, p arsenic may be used as a biomarker of arsenic exposure through drinking water.

Environmental Arsenic Exposure and Microbiota in Induced Sputum

Directory of Open Access Journals (Sweden)

Allison G. White

2014-02-01

Full Text Available Arsenic exposure from drinking water is associated with adverse respiratory outcomes, but it is unknown whether arsenic affects pulmonary microbiota. This exploratory study assessed the effect of exposure to arsenic in drinking water on bacterial diversity in the respiratory tract of non-smokers. Induced sputum was collected from 10 subjects with moderate mean household water arsenic concentration (21.1 ± 6.4 ppb and 10 subjects with low household water arsenic (2.4 ± 0.8 ppb. To assess microbiota in sputum, the V6 hypervariable region amplicons of bacterial 16s rRNA genes were sequenced using the Ion Torrent Personal Genome Machine. Microbial community differences between arsenic exposure groups were evaluated using QIIME and Metastats. A total of 3,920,441 sequence reads, ranging from 37,935 to 508,787 per sample for 316 chips after QIIME quality filtering, were taxonomically classified into 142 individual genera and five phyla. Firmicutes (22%, Proteobacteria (17% and Bacteriodetes (12% were the main phyla in all samples, with Neisseriaceae (15%, Prevotellaceae (12% and Veillonellacea (7% being most common at the genus level. Some genera, including Gemella, Lactobacillales, Streptococcus, Neisseria and Pasteurellaceae were elevated in the moderate arsenic exposure group, while Rothia, Prevotella, Prevotellaceae Fusobacterium and Neisseriaceae were decreased, although none of these differences was statistically significant. Future studies with more participants and a greater range of arsenic exposure are needed to further elucidate the effects of drinking water arsenic consumption on respiratory microbiota.

First-Trimester In Utero Exposure to Methylphenidate

DEFF Research Database (Denmark)

Dideriksen, Dorthe; Pottegård, Anton; Hallas, Jesper

2013-01-01

published, and safety during pregnancy has not been established. We systematically reviewed available data on birth outcome after human in utero exposure to methylphenidate. Systematic searches in PubMed/Embase were performed from origin to August 2012, and data from Michigan Medicaid recipients...

Binational Arsenic Exposure Survey: Methodology and Estimated Arsenic Intake from Drinking Water and Urinary Arsenic Concentrations

Directory of Open Access Journals (Sweden)

Robin B. Harris

2012-03-01

Full Text Available The Binational Arsenic Exposure Survey (BAsES was designed to evaluate probable arsenic exposures in selected areas of southern Arizona and northern Mexico, two regions with known elevated levels of arsenic in groundwater reserves. This paper describes the methodology of BAsES and the relationship between estimated arsenic intake from beverages and arsenic output in urine. Households from eight communities were selected for their varying groundwater arsenic concentrations in Arizona, USA and Sonora, Mexico. Adults responded to questionnaires and provided dietary information. A first morning urine void and water from all household drinking sources were collected. Associations between urinary arsenic concentration (total, organic, inorganic and estimated level of arsenic consumed from water and other beverages were evaluated through crude associations and by random effects models. Median estimated total arsenic intake from beverages among participants from Arizona communities ranged from 1.7 to 14.1 µg/day compared to 0.6 to 3.4 µg/day among those from Mexico communities. In contrast, median urinary inorganic arsenic concentrations were greatest among participants from Hermosillo, Mexico (6.2 µg/L whereas a high of 2.0 µg/L was found among participants from Ajo, Arizona. Estimated arsenic intake from drinking water was associated with urinary total arsenic concentration (p < 0.001, urinary inorganic arsenic concentration (p < 0.001, and urinary sum of species (p < 0.001. Urinary arsenic concentrations increased between 7% and 12% for each one percent increase in arsenic consumed from drinking water. Variability in arsenic intake from beverages and urinary arsenic output yielded counter intuitive results. Estimated intake of arsenic from all beverages was greatest among Arizonans yet participants in Mexico had higher urinary total and inorganic arsenic concentrations. Other contributors to urinary arsenic concentrations should be evaluated.

Assessment of human dietary exposure to arsenic through rice.

Science.gov (United States)

Davis, Matthew A; Signes-Pastor, Antonio J; Argos, Maria; Slaughter, Francis; Pendergrast, Claire; Punshon, Tracy; Gossai, Anala; Ahsan, Habibul; Karagas, Margaret R

2017-05-15

Rice accumulates 10-fold higher inorganic arsenic (i-As), an established human carcinogen, than other grains. This review summarizes epidemiologic studies that examined the association between rice consumption and biomarkers of arsenic exposure. After reviewing the literature we identified 20 studies, among them included 18 observational and 2 human experimental studies that reported on associations between rice consumption and an arsenic biomarker. Among individuals not exposed to contaminated water, rice is a source of i-As exposure - rice consumption has been consistently related to arsenic biomarkers, and the relationship has been clearly demonstrated in experimental studies. Early-life i-As exposure is of particular concern due to its association with lifelong adverse health outcomes. Maternal rice consumption during pregnancy also has been associated with infant toenail total arsenic concentrations indicating that dietary exposure during pregnancy results in fetal exposure. Thus, the collective evidence indicates that rice is an independent source of arsenic exposure in populations around the world and highlights the importance of investigating its affect on health. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Autism-Like Behavior and Epigenetic Changes Associated with Autism as Consequences of In Utero Exposure to Environmental Pollutants in a Mouse Model

Directory of Open Access Journals (Sweden)

Denise S. Hill

2015-01-01

Full Text Available We tested the hypothesis that in utero exposure to heavy metals increases autism-like behavioral phenotypes in adult animals and induces epigenetic changes in genes that have roles in the etiology of autism. Mouse dams were treated with cadmium, lead, arsenate, manganese, and mercury via drinking water from gestational days (E 1–10. Valproic acid (VPA injected intraperitoneally once on (E 8.5 served as a positive control. Young male offspring were tested for behavioral deficits using four standardized behavioral assays. In this study, in utero exposure to heavy metals resulted in multiple behavioral abnormalities that persisted into adulthood. VPA and manganese induced changes in perseverative/impulsive behavior and social dominance behavior, arsenic caused changes only in perseverative/impulsive behavior, and lead induced abnormalities in social interaction in comparison to the control animals. Brain samples from Mn, Pb, and VPA treated and control animals were evaluated for changes in CpG island methylation in promoter regions and associated changes in gene expression. The Chd7 gene, essential for neural crest cell migration and patterning, was found to be hypomethylated in each experimental animal tested compared to water-treated controls. Furthermore, distinct patterns of CpG island methylation yielded novel candidate genes for further investigation.

The effects of in utero bisphenol A exposure on reproductive capacity in several generations of mice

International Nuclear Information System (INIS)

Ziv-Gal, Ayelet; Wang, Wei; Zhou, Changqing; Flaws, Jodi A.

2015-01-01

In utero bisphenol A (BPA) exposure affects reproductive function in the first generation (F1) of mice; however, not many studies have examined the reproductive effects of BPA exposure on subsequent generations. In this study, pregnant mice (F0) were orally dosed with vehicle, BPA (0.5, 20, and 50 μg/kg/day) or diethylstilbestrol (DES; 0.05 μg/kg/day) daily from gestation day 11 until birth. F1 females were used to generate the F2 generation, and F2 females were used to generate the F3 generation. Breeding studies at the ages of 3, 6, and 9 months were conducted to evaluate reproductive capacity over time. Further, studies were conducted to evaluate pubertal onset, litter size, and percentage of dead pups; and to calculate pregnancy rate, and mating, fertility, and gestational indices. The results indicate that BPA exposure (0.5 and 50 μg/kg/day) significantly delayed the age at vaginal opening in the F3 generation compared to vehicle control. Both DES (0.05 μg/kg/day) and BPA (50 μg/kg/day) significantly delayed the age at first estrus in the F3 generation compared to vehicle control. BPA exposure reduced gestational index in the F1 and F2 generations compared to control. Further, BPA exposure (0.5 μg/kg/day) compromised the fertility index in the F3 generation compared to control. Finally, in utero BPA exposure reduced the ability of female mice to maintain pregnancies as they aged. Collectively, these data suggest that BPA exposure affects reproductive function in female mice and that some effects may be transgenerational in nature. - Highlights: • In utero BPA delayed vaginal opening in the F3 generation compared to control. • In utero BPA delayed estrus in the F3 generation compared to control. • In utero BPA reduced the ability of F1 and F2 female mice to maintain pregnancies. • In utero BPA compromised the ability of F3 female mice to become pregnant. • Some effects of in utero BPA may be transgenerational in nature

The effects of in utero bisphenol A exposure on reproductive capacity in several generations of mice

Energy Technology Data Exchange (ETDEWEB)

Ziv-Gal, Ayelet, E-mail: zivgal1@illinois.edu; Wang, Wei, E-mail: weiwang2@illinois.edu; Zhou, Changqing, E-mail: czhou27@illinois.edu; Flaws, Jodi A., E-mail: jflaws@illinois.edu

2015-05-01

In utero bisphenol A (BPA) exposure affects reproductive function in the first generation (F1) of mice; however, not many studies have examined the reproductive effects of BPA exposure on subsequent generations. In this study, pregnant mice (F0) were orally dosed with vehicle, BPA (0.5, 20, and 50 μg/kg/day) or diethylstilbestrol (DES; 0.05 μg/kg/day) daily from gestation day 11 until birth. F1 females were used to generate the F2 generation, and F2 females were used to generate the F3 generation. Breeding studies at the ages of 3, 6, and 9 months were conducted to evaluate reproductive capacity over time. Further, studies were conducted to evaluate pubertal onset, litter size, and percentage of dead pups; and to calculate pregnancy rate, and mating, fertility, and gestational indices. The results indicate that BPA exposure (0.5 and 50 μg/kg/day) significantly delayed the age at vaginal opening in the F3 generation compared to vehicle control. Both DES (0.05 μg/kg/day) and BPA (50 μg/kg/day) significantly delayed the age at first estrus in the F3 generation compared to vehicle control. BPA exposure reduced gestational index in the F1 and F2 generations compared to control. Further, BPA exposure (0.5 μg/kg/day) compromised the fertility index in the F3 generation compared to control. Finally, in utero BPA exposure reduced the ability of female mice to maintain pregnancies as they aged. Collectively, these data suggest that BPA exposure affects reproductive function in female mice and that some effects may be transgenerational in nature. - Highlights: • In utero BPA delayed vaginal opening in the F3 generation compared to control. • In utero BPA delayed estrus in the F3 generation compared to control. • In utero BPA reduced the ability of F1 and F2 female mice to maintain pregnancies. • In utero BPA compromised the ability of F3 female mice to become pregnant. • Some effects of in utero BPA may be transgenerational in nature.

Mthfr gene ablation enhances susceptibility to arsenic prenatal toxicity

Energy Technology Data Exchange (ETDEWEB)

Wlodarczyk, Bogdan J., E-mail: bwlodarczyk@austin.utexas.edu; Zhu, Huiping; Finnell, Richard H.

2014-02-15

Background: In utero exposure to arsenic is known to adversely affect reproductive outcomes. Evidence of arsenic teratogenicity varies widely and depends on individual genotypic differences in sensitivity to As. In this study, we investigated the potential interaction between 5,10-methylenetetrahydrofolate reductase (Mthfr) genotype and arsenic embryotoxicity using the Mthfr knockout mouse model. Methods: Pregnant dams were treated with sodium arsenate, and reproductive outcomes including: implantation, resorption, congenital malformation and fetal birth weight were recorded at E18.5. Results: When the dams in Mthfr{sup +/−} × Mthfr{sup +/−} matings were treated with 7.2 mg/kg As, the resorption rate increased to 43.4%, from a background frequency of 7.2%. The As treatment also induced external malformations (40.9%) and significantly lowered the average fetal birth weight among fetuses, without any obvious toxic effect on the dam. When comparing the pregnancy outcomes resulting from different mating scenarios (Mthfr{sup +/+} × Mthfr{sup +/−}, Mthfr{sup +/−} × Mthfr{sup +/−} and Mthfr{sup −/−} × {sup Mthfr+/−}) and arsenic exposure; the resorption rate showed a linear relationship with the number of null alleles (0, 1 or 2) in the Mthfr dams. Fetuses from nullizygous dams had the highest rate of external malformations (43%) and lowest average birth weight. When comparing the outcomes of reciprocal matings (nullizygote × wild-type versus wild-type × nullizygote) after As treatment, the null dams showed significantly higher rates of resorptions and malformations, along with lower fetal birth weights. Conclusions: Maternal genotype contributes to the sensitivity of As embryotoxicity in the Mthfr mouse model. The fetal genotype, however, does not appear to affect the reproductive outcome after in utero As exposure. - Highlights: • An interaction between Mthfr genotype and arsenic embryotoxicity is presented. • Maternal Mthfr genotype

Urinary arsenic profile affects the risk of urothelial carcinoma even at low arsenic exposure

International Nuclear Information System (INIS)

Pu, Y.-S.; Yang, S.-M.; Huang, Y.-K.; Chung, C.-J.; Huang, Steven K.; Chiu, Allen Wen-Hsiang; Yang, M.-H.; Chen, C.-J.; Hsueh, Y.-M.

2007-01-01

Arsenic exposure is associated with an increased risk of urothelial carcinoma (UC). To explore the association between individual risk and urinary arsenic profile in subjects without evident exposure, 177 UC cases and 313 age-matched controls were recruited between September 2002 and May 2004 for a case-control study. Urinary arsenic species including the following three categories, inorganic arsenic (As III + As V ), monomethylarsonic acid (MMA V ) and dimethylarsinic acid (DMA V ), were determined with high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Arsenic methylation profile was assessed by percentages of various arsenic species in the sum of the three categories measured. The primary methylation index (PMI) was defined as the ratio between MMA V and inorganic arsenic. Secondary methylation index (SMI) was determined as the ratio between DMA V and MMA V . Smoking is associated with a significant risk of UC in a dose-dependent manner. After multivariate adjustment, UC cases had a significantly higher sum of all the urinary species measured, higher percent MMA V , lower percent DMA V , higher PMI and lower SMI values compared with controls. Smoking interacts with the urinary arsenic profile in modifying the UC risk. Differential carcinogenic effects of the urinary arsenic profile, however, were seen more prominently in non-smokers than in smokers, suggesting that smoking is not the only major environmental source of arsenic contamination since the UC risk differs in non-smokers. Subjects who have an unfavorable urinary arsenic profile have an increased UC risk even at low exposure levels

An investigation of the health effects caused by exposure to arsenic from drinking water and coal combustion: arsenic exposure and metabolism.

Science.gov (United States)

Wei, Binggan; Yu, Jiangping; Kong, Chang; Li, Hairong; Yang, Linsheng; Guo, Zhiwei; Cui, Na; Xia, Yajuan; Wu, Kegong

2017-11-01

Few studies have been conducted to compare arsenic exposure, metabolism, and methylation in populations exposed to arsenic in drinking water and from coal combustion. Therefore, arsenic concentrations in the environment and arsenic speciation in the urine of subjects exposed to arsenic as a consequence of coal combustion in a rural area in Shaanxi province (CCA) and in drinking water in a rural area in Inner Mongolia (DWA) were investigated. The mean arsenic concentrations in drinking water, indoor air, and soil in CCA were 4.52 μg/L, 0.03 mg/m 3 , and 14.93 mg/kg, respectively. The mean arsenic concentrations in drinking water and soil in DWA were 144.71 μg/L and 10.19 mg/kg, respectively, while the level in indoor air was lower than the limit of detection. The total daily intakes of arsenic in DWA and CCA were 4.47 and 3.13 μg/day·kg, respectively. The mean urinary concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsenic acid (DMA), and total arsenic (TAs) for subjects with skin lesions in DWA were 50.41, 47.01, 202.66, and 300.08 μg/L. The concentrations for subjects without skin lesions were 49.76, 44.20, 195.60, and 289.56 μg/L, respectively. The %iAs, %MMA, and %DMA in the TAs in the urine of subjects from CCA were 12.24, 14.73, and 73.03%, while the corresponding values from DWA were 17.54, 15.57, and 66.89%, respectively. The subjects in DWA typically had a higher %iAs and %MMA, and a lower %DMA, and primary and secondary methylation index (PMI and SMI) than the subjects in CCA. It was concluded that the arsenic methylation efficiency of subjects in DWA and CCA was significantly influenced by chronic exposure to high levels of arsenic in the environment. The lower PMI and SMI values in DWA revealed lower arsenic methylation capacity due to ingestion of arsenic in drinking water. However, it remained unclear if the differences in arsenic metabolism between the two groups were due to differences in exposure levels

In utero bisphenol A exposure disrupts germ cell nest breakdown and reduces fertility with age in the mouse

Energy Technology Data Exchange (ETDEWEB)

Wang, Wei, E-mail: weiwang2@illinois.edu; Hafner, Katlyn S., E-mail: katlynhafner@gmail.com; Flaws, Jodi A., E-mail: jflaws@illinois.edu

2014-04-15

Bisphenol A (BPA) is a known reproductive toxicant in rodents. However, the effects of in utero BPA exposure on early ovarian development and the consequences of such exposure on female reproduction in later reproductive life are unclear. Thus, we determined the effects of in utero BPA exposure during a critical developmental window on germ cell nest breakdown, a process required for establishment of the finite primordial follicle pool, and on female reproduction. Pregnant FVB mice (F0) were orally dosed daily with tocopherol-striped corn oil (vehicle), diethylstilbestrol (DES; 0.05 μg/kg, positive control), or BPA (0.5, 20, and 50 μg/kg) from gestational day 11 until birth. Ovarian morphology and gene expression profiles then were examined in F1 female offspring on postnatal day (PND) 4 and estrous cyclicity was examined daily after weaning for 30 days. F1 females were also subjected to breeding studies with untreated males at three to nine months. The results indicate that BPA inhibits germ cell nest breakdown via altering expression of selected apoptotic factors. BPA also significantly advances the age of first estrus, shortens the time that the females remain in estrus, and increases the time that the females remain in metestrus and diestrus compared to controls. Further, F1 females exposed to low doses of BPA exhibit various fertility problems and have a significantly higher percentage of dead pups compared to controls. These results indicate that in utero exposure to low doses of BPA during a critical ovarian developmental window interferes with early ovarian development and reduces fertility with age. - Highlights: • In utero BPA exposure inhibits germ cell nest breakdown in female mouse offspring. • In utero BPA exposure alters expression of apoptosis regulators in the ovaries of mouse offspring. • In utero BPA exposure advances first estrus age and alters cyclicity in mouse offspring. • In utero BPA exposure causes various fertility problems in

In utero bisphenol A exposure disrupts germ cell nest breakdown and reduces fertility with age in the mouse

International Nuclear Information System (INIS)

Wang, Wei; Hafner, Katlyn S.; Flaws, Jodi A.

2014-01-01

Bisphenol A (BPA) is a known reproductive toxicant in rodents. However, the effects of in utero BPA exposure on early ovarian development and the consequences of such exposure on female reproduction in later reproductive life are unclear. Thus, we determined the effects of in utero BPA exposure during a critical developmental window on germ cell nest breakdown, a process required for establishment of the finite primordial follicle pool, and on female reproduction. Pregnant FVB mice (F0) were orally dosed daily with tocopherol-striped corn oil (vehicle), diethylstilbestrol (DES; 0.05 μg/kg, positive control), or BPA (0.5, 20, and 50 μg/kg) from gestational day 11 until birth. Ovarian morphology and gene expression profiles then were examined in F1 female offspring on postnatal day (PND) 4 and estrous cyclicity was examined daily after weaning for 30 days. F1 females were also subjected to breeding studies with untreated males at three to nine months. The results indicate that BPA inhibits germ cell nest breakdown via altering expression of selected apoptotic factors. BPA also significantly advances the age of first estrus, shortens the time that the females remain in estrus, and increases the time that the females remain in metestrus and diestrus compared to controls. Further, F1 females exposed to low doses of BPA exhibit various fertility problems and have a significantly higher percentage of dead pups compared to controls. These results indicate that in utero exposure to low doses of BPA during a critical ovarian developmental window interferes with early ovarian development and reduces fertility with age. - Highlights: • In utero BPA exposure inhibits germ cell nest breakdown in female mouse offspring. • In utero BPA exposure alters expression of apoptosis regulators in the ovaries of mouse offspring. • In utero BPA exposure advances first estrus age and alters cyclicity in mouse offspring. • In utero BPA exposure causes various fertility problems in

Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

Energy Technology Data Exchange (ETDEWEB)

Olivas-Calderón, Edgar, E-mail: edgar_olivascalderon@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico); Recio-Vega, Rogelio, E-mail: rrecio@yahoo.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gandolfi, A. Jay, E-mail: gandolfi@pharmacy.arizona.edu [Southwest Environmental Health Science Center, University of Arizona, Tucson, AZ (United States); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Lantz, R. Clark, E-mail: lantz@email.arizona.edu [Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ (United States); González-Cortes, Tania, E-mail: taniagc2201@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gonzalez-De Alba, Cesar, E-mail: cesargonzalezalba@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Froines, John R., E-mail: jfroines@ucla.edu [Center for Environmental and Occupational Health, School of Public Health, University of California at Los Angeles, Los Angeles, CA (United States); Espinosa-Fematt, Jorge A., E-mail: dr.jorge.espinosa@gmail.com [School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico)

2015-09-01

Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels

Maternal in utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate affects the blood pressure of adult male offspring

Energy Technology Data Exchange (ETDEWEB)

Martinez–Arguelles, D.B. [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); McIntosh, M.; Rohlicek, C.V. [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Pediatrics, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Culty, M. [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Zirkin, B.R. [Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205 (United States); Papadopoulos, V., E-mail: vassilios.papadopoulos@mcgill.ca [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205 (United States)

2013-01-01

Di-(2-ethylhexyl) phthalate (DEHP) is used industrially to add flexibility to polyvinyl chloride (PVC) polymers and is ubiquitously found in the environment, with evidence of prenatal, perinatal and early infant exposure in humans. In utero exposure to DEHP decreases circulating testosterone levels in the adult rat. In addition, DEHP reduces the expression of the angiotensin II receptors in the adrenal gland, resulting in decreased circulating aldosterone levels. The latter may have important effects on water and electrolyte balance as well as systemic arterial blood pressure. Therefore, we determined the effects of in utero exposure to DEHP on systemic arterial blood pressure in the young (2 month-old) and older (6.5 month-old) adult rats. Sprague-Dawley pregnant dams were exposed from gestational day 14 until birth to 300 mg DEHP/kg/day. Blood pressure, heart rate, and activity data were collected using an intra-aortal transmitter in the male offspring at postnatal day (PND) 60 and PND200. A low (0.01%) and high-salt (8%) diet was used to challenge the animals at PND200. In utero exposure to DEHP resulted in reduced activity at PND60. At PND200, systolic and diastolic systemic arterial pressures as well as activity were reduced in response to DEHP exposure. This is the first evidence showing that in utero exposure to DEHP has cardiovascular and behavioral effects in the adult male offspring. Highlights: ► In utero exposure to 300 mg DEHP/kg/day decreases activity at postnatal day 60. ► In utero exposure to DEHP decreases aldosterone levels at postnatal day 200. ► In utero exposure to DEHP decreases systolic blood pressure at postnatal day 200. ► An 8% salt diet recovers the decreased blood pressure at postnatal day 200.

DEHP exposure in utero disturbs sex determination and is potentially linked with precocious puberty in female mice

International Nuclear Information System (INIS)

Wang, Yongan; Yang, Qing; Liu, Wei; Yu, Mingxi; Zhang, Zhou; Cui, Xiaoyu

2016-01-01

Human's ubiquitous exposure to di (2-ethylhexyl) phthalate (DEHP) is thought to be associated with female reproductive toxicity. Previous studies found that DEHP inhibited follicle growth and decreased estradiol levels in adult female mice. However, limited information is available on the link between in utero DEHP exposure and ovarian development in female mouse offspring. The present study evaluates the disturbances in regulatory genes involved in female sex determination and the ovarian outcomes in fetal and postnatal female mice treated with in utero DEHP exposure. Pregnant mice were exposed to DEHP by gavage, with the dosage regime beginning at human relevant exposure levels. After in utero DEHP exposure, increased follicular atresia was observed in the female pups at postnatal days (PND) 21. Foxl2 expression was significantly upregulated, and Fst was significantly downregulated by DEHP above 2 mg/kg/d at PND 1 and 21. This suggests that lesion of granulosa cell differentiation and disturbance of follicle development in postnatal female mice. The expression of Cyp11a1 and Star were significantly downregulated by in utero DEHP exposure, indicating effects on estradiol biosynthesis. The female sex determination pathway was disturbed in fetus by DEHP at 2 mg/kg/d and above during the critical time window of sex determination causing significant upregulation of Foxl2, Wnt4, β-catenin and Fst. Furthermore, the increased expression of Wnt4 was supported by whole-mount in situ hybridization (WISH). These results suggest a possible association between in utero DEHP exposure and precocious puberty in the postnatal life of mice offspring, where disturbance of the sex determination regulating pathway acted as an important mechanism. - Highlights: • Maternal exposure to di (2-ethylhexyl) phthalate disturbs fetus sex determination. • DEHP upregulated Foxl2 expression potentially disturbs postnatal granulosa cell differentiation. • DEHP accelerated medulla

DEHP exposure in utero disturbs sex determination and is potentially linked with precocious puberty in female mice

Energy Technology Data Exchange (ETDEWEB)

Wang, Yongan [Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of Environmental Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024 (China); Yang, Qing [School of Life Science and Biotechnology, Dalian University of Technology, Dalian, Liaoning 116024 (China); Liu, Wei, E-mail: liu_wei@dlut.edu.cn [Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of Environmental Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024 (China); Yu, Mingxi; Zhang, Zhou; Cui, Xiaoyu [Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of Environmental Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024 (China)

2016-09-15

Human's ubiquitous exposure to di (2-ethylhexyl) phthalate (DEHP) is thought to be associated with female reproductive toxicity. Previous studies found that DEHP inhibited follicle growth and decreased estradiol levels in adult female mice. However, limited information is available on the link between in utero DEHP exposure and ovarian development in female mouse offspring. The present study evaluates the disturbances in regulatory genes involved in female sex determination and the ovarian outcomes in fetal and postnatal female mice treated with in utero DEHP exposure. Pregnant mice were exposed to DEHP by gavage, with the dosage regime beginning at human relevant exposure levels. After in utero DEHP exposure, increased follicular atresia was observed in the female pups at postnatal days (PND) 21. Foxl2 expression was significantly upregulated, and Fst was significantly downregulated by DEHP above 2 mg/kg/d at PND 1 and 21. This suggests that lesion of granulosa cell differentiation and disturbance of follicle development in postnatal female mice. The expression of Cyp11a1 and Star were significantly downregulated by in utero DEHP exposure, indicating effects on estradiol biosynthesis. The female sex determination pathway was disturbed in fetus by DEHP at 2 mg/kg/d and above during the critical time window of sex determination causing significant upregulation of Foxl2, Wnt4, β-catenin and Fst. Furthermore, the increased expression of Wnt4 was supported by whole-mount in situ hybridization (WISH). These results suggest a possible association between in utero DEHP exposure and precocious puberty in the postnatal life of mice offspring, where disturbance of the sex determination regulating pathway acted as an important mechanism. - Highlights: • Maternal exposure to di (2-ethylhexyl) phthalate disturbs fetus sex determination. • DEHP upregulated Foxl2 expression potentially disturbs postnatal granulosa cell differentiation. • DEHP accelerated medulla

Blood Pressure Associated with Arsenic Methylation and Arsenic Metabolism Caused by Chronic Exposure to Arsenic in Tube Well Water.

Science.gov (United States)

Wei, Bing Gan; Ye, Bi Xiong; Yu, Jiang Ping; Yang, Lin Sheng; Li, Hai Rong; Xia, Ya Juan; Wu, Ke Gong

2017-05-01

The effects of arsenic exposure from drinking water, arsenic metabolism, and arsenic methylation on blood pressure (BP) were observed in this study. The BP and arsenic species of 560 participants were determined. Logistic regression analysis was applied to estimate the odds ratios of BP associated with arsenic metabolites and arsenic methylation capability. BP was positively associated with cumulative arsenic exposure (CAE). Subjects with abnormal diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse pressure (PP) usually had higher urinary iAs (inorganic arsenic), MMA (monomethylated arsenic), DMA (dimethylated arsenic), and TAs (total arsenic) than subjects with normal DBP, SBP, and PP. The iAs%, MMA%, and DMA% differed slightly between subjects with abnormal BP and those with normal BP. The PMI and SMI were slightly higher in subjects with abnormal PP than in those with normal PP. Our findings suggest that higher CAE may elevate BP. Males may have a higher risk of abnormal DBP, whereas females have a higher risk of abnormal SBP and PP. Higher urinary iAs may increase the risk of abnormal BP. Lower PMI may elevate the BP. However, higher SMI may increase the DBP and SBP, and lower SMI may elevate the PP. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

In Utero Exposure to Cadmium, Mammary Gland Development, and Breast Cancer Risk

National Research Council Canada - National Science Library

Webster, Jennifer D

2007-01-01

.... Previous studies have shown that in utero exposure to cadmium at the levels present in some human environments accelerated puberty onset and altered some of the indicators of mammary gland development in rats...

Assessment of arsenic exposures and controls in gallium arsenide production.

Science.gov (United States)

Sheehy, J W; Jones, J H

1993-02-01

The electronics industry is expanding the use of gallium arsenide in the production of optoelectronic devices and integrated circuits. Workers in the electronics industry using gallium arsenide are exposed to hazardous substances such as arsenic, arsine, and various acids. Arsenic requires stringent controls to minimize exposures (the current OSHA PEL for arsenic is 10 micrograms/m3 and the NIOSH REL is 2 micrograms/m3 ceiling). Inorganic arsenic is strongly implicated in respiratory tract and skin cancer. For these reasons, NIOSH researchers conducted a study of control systems for facilities using gallium arsenide. Seven walk-through surveys were performed to identify locations for detailed study which appeared to have effective controls; three facilities were chosen for in-depth evaluation. The controls were evaluated by industrial hygiene sampling. Including personal breathing zone and area air sampling for arsenic and arsine; wipe samples for arsenic also were collected. Work practices and the use of personal protective equipment were documented. This paper reports on the controls and the arsenic exposure results from the evaluation of the following gallium arsenide processes: Liquid Encapsulated Czochralski (LEC) and Horizontal Bridgeman (HB) crystal growing, LEC cleaning operations, ingot grinding/wafer sawing, and epitaxy. Results at one plant showed that in all processes except epitaxy, average arsenic exposures were at or above the OSHA action level of 5 micrograms/m3. While cleaning the LEC crystal pullers, the average potential arsenic exposure of the cleaning operators was 100 times the OSHA PEL. At the other two plants, personal exposures for arsenic were well controlled in LEC, LEC cleaning, grinding/sawing, and epitaxy operations.

Motor development following in utero exposure to organochlorines

DEFF Research Database (Denmark)

Høyer, Birgit Bjerre; Ramlau-Hansen, Cecilia Høst; Pedersen, Henning Sloth

2015-01-01

of child age at the first time of crawling, standing-up and walking. RESULTS: We saw no associations between tertiles of CB-153 and p,p'-DDE or log-transformed exposures and retrospective reports of the developmental milestones crawling, standing-up and walking in infancy or the motor skills measured...... as developmental coordination disorder at young school age. CONCLUSIONS: In utero exposure to CB-153 and p,p'-DDE was not associated with parentally retrospectively assessed developmental milestones in infancy or parentally assessed motor skills at young school age. The use of a more sensitive outcome measure may......BACKGROUND: Prior studies on the association between prenatal exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) and child motor development have found contradicting results. Using data collected in the INUENDO cohort in Kharkiv (Ukraine), Warsaw (Poland...

Environmental exposure to arsenic and chromium in an industrial area

OpenAIRE

Vimercati, Luigi; Gatti, Maria F; Gagliardi, Tommaso; Cuccaro, Francesco; De Maria, Luigi; Caputi, Antonio; Quarato, Marco; Baldassarre, Antonio

2017-01-01

Arsenic and chromium are widespread environmental contaminants that affect global health due to their toxicity and carcinogenicity. To date, few studies have investigated exposure to arsenic and chromium in a population residing in a high-risk environmental area. The aim of this study is to evaluate the exposure to arsenic and chromium in the general population with no occupational exposure to these metals, resident in the industrial area of Taranto, Southern Italy, through biological monitor...

MDI Biological Laboratory Arsenic Summit: Approaches to Limiting Human Exposure to Arsenic

OpenAIRE

Stanton, Bruce A.

2015-01-01

This report is the outcome of the meeting: “Environmental and Human Health Consequences of Arsenic”, held at the MDI Biological Laboratory in Salisbury Cove, Maine, August 13–15, 2014. Human exposure to arsenic represents a significant health problem worldwide that requires immediate attention according to the World Health Organization (WHO). One billion people are exposed to arsenic in food and more than 200 million people ingest arsenic via drinking water at concentrations greater than inte...

Arsenic exposure, urinary arsenic speciation, and peripheral vascular disease in blackfoot disease-hyperendemic villages in Taiwan

International Nuclear Information System (INIS)

Tseng, C.-H.; Huang, Y.-K.; Huang, Y.-L.; Chung, C.-J.; Yang, M.-H.; Chen, C.-J.; Hsueh, Y.-M.

2005-01-01

Long-term exposure to ingested inorganic arsenic is associated with peripheral vascular disease (PVD) in the blackfoot disease (BFD)-hyperendemic area in Taiwan. This study further examined the interaction between arsenic exposure and urinary arsenic speciation on the risk of PVD. A total of 479 (220 men and 259 women) adults residing in the BFD-hyperendemic area were studied. Doppler ultrasound was used to diagnose PVD. Arsenic exposure was estimated by an index of cumulative arsenic exposure (CAE). Urinary levels of total arsenic, inorganic arsenite (As III ) and arsenate (As V ), monomethylarsonic acid (MMA V ), and dimethylarsinic acid (DMA V ) were determined. Primary methylation index [PMI = MMA V /(As III + As V )] and secondary methylation index (SMI = DMA V /MMA V ) were calculated. The association between PVD and urinary arsenic parameters was evaluated with consideration of the interaction with CAE and the confounding effects of age, sex, body mass index, total cholesterol, triglycerides, cigarette smoking, and alcohol consumption. Results showed that aging was associated with a diminishing capacity to methylate inorganic arsenic and women possessed a more efficient arsenic methylation capacity than men did. PVD risk increased with a higher CAE and a lower capacity to methylate arsenic to DMA V . The multivariate-adjusted odds ratios for CAE of 0, 0.1-15.4, and >15.4 mg/L x year were 1.00, 3.41 (0.74-15.78), and 4.62 (0.96-22.21), respectively (P 6.93, PMI > 1.77 and SMI > 6.93, PMI > 1.77 and SMI ≤ 6.93, and PMI ≤ 1.77 and SMI ≤ 6.93 were 1.00, 2.93 (0.90-9.52), 2.85 (1.05-7.73), and 3.60 (1.12-11.56), respectively (P V have a higher risk of developing PVD in the BFD-hyperendemic area in Taiwan

Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

International Nuclear Information System (INIS)

Hsieh, Yi-Chen; Lien, Li-Ming; Chung, Wen-Ting; Hsieh, Fang-I; Hsieh, Pei-Fan; Wu, Meei-Maan; Tseng, Hung-Pin; Chiou, Hung-Yi; Chen, Chien-Jen

2011-01-01

Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 μg/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 μg/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 μg/l). - Highlights: →Arsenic metabolic genes might be associated with carotid atherosclerosis. → A case

Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

Energy Technology Data Exchange (ETDEWEB)

Hsieh, Yi-Chen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Lien, Li-Ming [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan (China); Chung, Wen-Ting [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsieh, Fang-I; Hsieh, Pei-Fan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Wu, Meei-Maan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan (China); Tseng, Hung-Pin [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China); Chiou, Hung-Yi, E-mail: hychiou@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Chen, Chien-Jen [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)

2011-08-15

Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields

Arsenic exposure to smelter workers. Clinical and neurophysiological studies

Energy Technology Data Exchange (ETDEWEB)

Blom, S.; Lagerkvist, B.; Linderholm, H.

1985-08-01

Forty-seven copper smelter workers, exposed to airborne arsenic for 8-40 years, were examined clinically with electromyography, and the motor and sensory conduction velocities in their arms and legs were determined. Fifty age-matched industrial workers not exposed to arsenic formed a reference group. The level of arsenic in the air at the smeltery was estimated to be below 500 micrograms/mT before 1975 and approximately 50 micrograms/mT thereafter. Urine analyses of arsenic showed a mean value of 71 micrograms/l (1 mumol/l) in the exposed group; this value is lower than that found in earlier studies reporting clinically detectable neuropathy. A slightly reduced nerve conduction velocity in two or more peripheral nerves was more common among the arsenic workers than the referents, and a statistically significant correlation between cumulative exposure to arsenic and reduced nerve conduction velocity in three peripheral motor nerves was found. This occurrence was interpreted as a sign of slight subclinical neuropathy. In conclusion the risk of clinically significant neuropathy is small when exposure is kept below 50 micrograms/mT in workroom air. The subclinical findings may be of interest in relation to the prevention of early adverse health effects from arsenic exposure.

Dietary Arsenic Exposure in Bangladesh

OpenAIRE

Kile, Molly L.; Houseman, E. Andres; Breton, Carrie V.; Smith, Thomas; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Christiani, David C.

2007-01-01

Background Millions of people in Bangladesh are at risk of chronic arsenic toxicity from drinking contaminated groundwater, but little is known about diet as an additional source of As exposure. Methods We employed a duplicate diet survey to quantify daily As intake in 47 women residing in Pabna, Bangladesh. All samples were analyzed for total As, and a subset of 35 samples were measured for inorganic arsenic (iAs) using inductively coupled plasma mass spectrometry equipped with a dynamic rea...

Arsenic: bioaccessibility from seaweed and rice, dietary exposure calculations and risk assessment.

Science.gov (United States)

Brandon, Esther F A; Janssen, Paul J C M; de Wit-Bos, Lianne

2014-01-01

Arsenic is a metalloid that occurs in food and the environment in different chemical forms. Inorganic arsenic is classified as a class I carcinogen. The inorganic arsenic intake from food and drinking water varies depending on the geographic arsenic background. Non-dietary exposure to arsenic is likely to be of minor importance for the general population within the European Union. In Europe, arsenic in drinking water is on average low, but food products (e.g. rice and seaweed) are imported from all over the world including from regions with naturally high arsenic levels. Therefore, specific populations living in Europe could also have a high exposure to inorganic arsenic due to their consumption pattern. Current risk assessment is based on exposure via drinking water. For a good estimation of the risks of arsenic in food, it is important to investigate if the bioavailability of inorganic arsenic from food is different from drinking water. The present study further explores the issue of European dietary exposure to inorganic arsenic via rice and seaweed and its associated health risks. The bioavailability of inorganic arsenic was measured in in vitro digestion experiments. The data indicate that the bioavailability of inorganic arsenic is similar for rice and seaweed compared with drinking water. The calculated dietary intake for specific European Union populations varied between 0.44 and 4.51 µg kg⁻¹ bw day⁻¹. The margins of exposure between the inorganic intake levels and the BMDL0.5 values as derived by JECFA are low. Decreasing the intake of inorganic arsenic via Hijiki seaweed could be achieved by setting legal limits similar to those set for rice by the Codex Alimentarius Commission in July 2014.

In Utero Exposure to Exosomal and B-Cell Alloantigens Lessens Alloreactivity of Recipients’ Lymphocytes Rather than Confers Allograft Tolerance

Directory of Open Access Journals (Sweden)

Jeng-Chang Chen

2018-03-01

Full Text Available According to actively acquired tolerance, antigen exposure before full immune development in fetal or early neonatal life will cause tolerance to this specific antigen. In this study, we aimed to examine whether allogeneic tolerance could be elicited by in utero exposure to surface MHC antigens of allogenic cells or soluble form of MHC exosomes. Gestational day 14 FVB/N fetuses were subjected to intraperitoneal injection of allogeneic major histocompatibility complex (MHC exosomes or highly enriched B-cells. Postnatally, the recipients were examined for the immune responses to donor alloantigens by lymphocyte proliferative reactions and skin transplantation. In utero exposure to allogeneic MHC exosomes abolished the alloreactivity of recipients’ lymphocytes to the alloantigens, but could not confer skin allograft tolerance. In utero transplantation of highly enriched allogeneic B-cells generated low-level B-cell chimerism in the recipients. However, it only extended the survivals of skin allograft by a few days despite the lack of donor-specific alloreactivity of recipients’ lymphocyte. Thus, an early in utero contact with exosomal or B-cell alloantigens did not lead to full skin tolerance but rather, at best, only to delayed skin rejection in the presence of microchimerism made by B-cell inocula. These results argued against the theory of actively acquired tolerance, and implicated that in utero exposure to marrow cells in previous studies was a unique model of allo-tolerance induction that involved the establishment of significant hematopoietic chimerism. Taken together with the discovery of in utero sensitization to ovalbumin in our previous studies, the immunological consequences of fetal exposure to foreign antigens might vary according to the type or nature of antigens introduced.

In Utero Exposure to Exosomal and B-Cell Alloantigens Lessens Alloreactivity of Recipients' Lymphocytes Rather than Confers Allograft Tolerance.

Science.gov (United States)

Chen, Jeng-Chang; Ou, Liang-Shiou; Chan, Cheng-Chi; Kuo, Ming-Ling; Tseng, Li-Yun; Chang, Hsueh-Ling

2018-01-01

According to actively acquired tolerance, antigen exposure before full immune development in fetal or early neonatal life will cause tolerance to this specific antigen. In this study, we aimed to examine whether allogeneic tolerance could be elicited by in utero exposure to surface MHC antigens of allogenic cells or soluble form of MHC exosomes. Gestational day 14 FVB/N fetuses were subjected to intraperitoneal injection of allogeneic major histocompatibility complex (MHC) exosomes or highly enriched B-cells. Postnatally, the recipients were examined for the immune responses to donor alloantigens by lymphocyte proliferative reactions and skin transplantation. In utero exposure to allogeneic MHC exosomes abolished the alloreactivity of recipients' lymphocytes to the alloantigens, but could not confer skin allograft tolerance. In utero transplantation of highly enriched allogeneic B-cells generated low-level B-cell chimerism in the recipients. However, it only extended the survivals of skin allograft by a few days despite the lack of donor-specific alloreactivity of recipients' lymphocyte. Thus, an early in utero contact with exosomal or B-cell alloantigens did not lead to full skin tolerance but rather, at best, only to delayed skin rejection in the presence of microchimerism made by B-cell inocula. These results argued against the theory of actively acquired tolerance, and implicated that in utero exposure to marrow cells in previous studies was a unique model of allo-tolerance induction that involved the establishment of significant hematopoietic chimerism. Taken together with the discovery of in utero sensitization to ovalbumin in our previous studies, the immunological consequences of fetal exposure to foreign antigens might vary according to the type or nature of antigens introduced.

Assessment of Nutritional Status of Infants Living in Arsenic-Contaminated Areas in Bangladesh and Its Association with Arsenic Exposure

Science.gov (United States)

Milton, Abul Hasnat; Attia, John; Alauddin, Mohammad; McEvoy, Mark; McElduff, Patrick; Hussain, Sumaira; Akhter, Ayesha; Akter, Shahnaz; Islam, M. Munirul; Ahmed, AM Shamsir; Iyengar, Vasu; Islam, Md Rafiqul

2018-01-01

Data is scarce on early life exposure to arsenic and its association with malnutrition during infancy. This study followed the nutritional status of a cohort of 120 infants from birth to 9 months of age in an arsenic contaminated area in Bangladesh. Anthropometric data was collected at 3, 6 and 9 months of the infant’s age for nutritional assessment whereas arsenic exposure level was assessed via tube well drinking water arsenic concentration at the initiation of the study. Weight and height measurements were converted to Z-scores of weight for age (WAZ-underweight), height for age (HAZ-stunting), weight for height (WHZ-wasting) for children by comparing with WHO growth standard. Arsenic exposure levels were categorized as <50 μg/L and ≥50 μg/L. Stunting rates (<−2 SD) were 10% at 3 months and 44% at both 6 and 9 months. Wasting rates (<−2 SD) were 23.3% at 3 months and underweight rates (<−2 SD) were 25% and 10% at 3 and 6 months of age, respectively. There was a significant association of stunting with household drinking water arsenic exposure ≥50 μg/L at age of 9 months (p = 0.009). Except for stunting at 9 months of age, we did not find any significant changes in other nutritional indices over time or with levels of household arsenic exposure in this study. Our study suggests no association between household arsenic exposure and under-nutrition during infancy; with limiting factors being small sample size and short follow-up. Difference in stunting at 9 months by arsenic exposure at ≥50 μg/L might be a statistical incongruity. Further longitudinal studies are warranted to establish any association. PMID:29301293

Environmental arsenic exposure, selenium and sputum alpha-1 antitrypsin

DEFF Research Database (Denmark)

Burgess, Jefferey L; Kurzius-Spencer, Margaret; Poplin, Gerald S

2014-01-01

Exposure to arsenic in drinking water is associated with increased respiratory disease. Alpha-1 antitrypsin (AAT) protects the lung against tissue destruction. The objective of this study was to determine whether arsenic exposure is associated with changes in airway AAT concentration and whether...... this relationship is modified by selenium. A total of 55 subjects were evaluated in Ajo and Tucson, Arizona. Tap water and first morning void urine were analyzed for arsenic species, induced sputum for AAT and toenails for selenium and arsenic. Household tap-water arsenic, toenail arsenic and urinary inorganic...... arsenic and metabolites were significantly higher in Ajo (20.6±3.5 μg/l, 0.54±0.77 μg/g and 27.7±21.2 μg/l, respectively) than in Tucson (3.9±2.5 μg/l, 0.16±0.20 μg/g and 13.0±13.8 μg/l, respectively). In multivariable models, urinary monomethylarsonic acid (MMA) was negatively, and toenail selenium...

Site-specific data confirm arsenic exposure predicted by the U.S. Environmental Protection Agency.

Science.gov (United States)

Walker, S; Griffin, S

1998-03-01

The EPA uses an exposure assessment model to estimate daily intake to chemicals of potential concern. At the Anaconda Superfund site in Montana, the EPA exposure assessment model was used to predict total and speciated urinary arsenic concentrations. Predicted concentrations were then compared to concentrations measured in children living near the site. When site-specific information on concentrations of arsenic in soil, interior dust, and diet, site-specific ingestion rates, and arsenic absorption rates were used, measured and predicted urinary arsenic concentrations were in reasonable agreement. The central tendency exposure assessment model successfully described the measured urinary arsenic concentration for the majority of children at the site. The reasonable maximum exposure assessment model successfully identified the uppermost exposed population. While the agreement between measured and predicted urinary arsenic is good, it is not exact. The variables that were identified which influenced agreement included soil and dust sample collection methodology, daily urinary volume, soil ingestion rate, and the ability to define the exposure unit. The concentration of arsenic in food affected agreement between measured and predicted total urinary arsenic, but was not considered when comparing measured and predicted speciated urinary arsenic. Speciated urinary arsenic is the recommended biomarker for recent inorganic arsenic exposure. By using site-specific data in the exposure assessment model, predicted risks from exposure to arsenic were less than predicted risks would have been if the EPA's default values had been used in the exposure assessment model. This difference resulted in reduced magnitude and cost of remediation while still protecting human health.

Vinclozolin exposure in utero induces postpubertal prostatitis and reduces sperm production via a reversible hormone-regulated mechanism.

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Cowin, Prue A; Gold, Elspeth; Aleksova, Jasna; O'Bryan, Moira K; Foster, Paul M D; Scott, Hamish S; Risbridger, Gail P

2010-02-01

Vinclozolin is an endocrine-disrupting chemical (EDC) that binds with high affinity to the androgen receptor (AR) and blocks the action of gonadal hormones on male reproductive organs. An alternative mechanism of action of Vinclozolin involves transgenerational effects on the male reproductive tract. We previously reported in utero Vinclozolin exposure-induced prostatitis (prostate inflammation) in postpubertal rats concurrent with down-regulation of AR and increased nuclear factor-kappaB activation. We postulated the male reproductive abnormalities induced by in utero Vinclozolin exposure could be reversed by testosterone supplementation, in contrast to the permanent modifications involving DNA methyltransferases (Dnmts) described by others. To test this hypothesis, we administered high-dose testosterone at puberty to Vinclozolin-treated rats and determined the effect on anogenital distance (AGD); testicular germ cell apoptosis, concentration of elongated spermatids, and the onset of prostatitis. Concurrently we examined Dnmt1, -3A, -3B, and -3L mRNA expression. Consistent with previous reports, in utero exposure to Vinclozolin significantly reduced AGD, increased testicular germ cell apoptosis 3-fold, reduced elongated spermatid number by 40%, and induced postpubertal prostatitis in 100% of exposed males. Administration of high-dose testosterone (25 mg/kg) at puberty normalized AGD, reduced germ cell apoptosis, and restored elongated spermatid number. Testosterone restored AR and nuclear factor-kappaB expression in the prostate and abolished Vinclozolin-induced prostatitis. Altered Dnmt expression was evident with in utero Vinclozolin exposure and was not normalized after testosterone treatment. These data demonstrate in utero Vinclozolin-induced male reproductive tract abnormalities are AR mediated and reversible and involve a mechanism independent of Dnmt expression.

Negative trends for in utero Chernobyl exposure and early childhood leukaemia in Western Germany

International Nuclear Information System (INIS)

Burkart, W.; Steiner, M.; Grosche, B.; Kaletsch, U.; Michaelis, J.

1997-01-01

A recent report in Nature linked increased incidence of early infant leukaemia in Greece with 137 Cs fallout density, attributing the effect to an increased in utero exposure to ionizing radiation from the Chernobyl accident. As a validation exercise in a similarly affected region, we performed an analysis based on the data of the Childhood Cancer Registry for Western Germany. Using the same definitions as Petridou et al. we also observed an increased incidence of infant leukaemia in a cohort of children who were born after the Chernobyl accident. More detailed analyses of embryonic/foetal doses regarding areas of different contamination levels and dose rate gradients with time since the accident showed non-significant negative trends with exposure. Therefore, we conclude that the observed effect was not caused by exposure to ionizing radiation due to the Chernobyl accident. Dosimetric considerations per se, based on careful assessment of in utero doses in three different exposure categories, show doses much too small relative to natural radiation exposures to account for a significant effect on leukaemia rates. (author)

The die is cast: arsenic exposure in early life and disease susceptibility.

Science.gov (United States)

Thomas, David J

2013-12-16

Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for the development and progression of disease in both species. Mode of action and dosimetric studies in the mouse may help assess the role of age at exposure as a factor in susceptibility to the toxic and carcinogenic effects of arsenic in humans.

The effect of diesel (DE) exposure in utero on reproductive and developmental immunotoxicity

Science.gov (United States)

Epidemiology studies are beginning to show that in utero exposure to traffic related pollutants might increase the incidence of immune mediated lung diseases. Time pregnant BALB/c mice were exposed to air or two concentrations of diesel exhaust (0.5 and 2 mg/m3...

The Association of Arsenic Exposure and Arsenic Metabolism with the Metabolic Syndrome and its Individual Components: Prospective Evidence from the Strong Heart Family Study.

Science.gov (United States)

Spratlen, Miranda J; Grau-Perez, Maria; Best, Lyle G; Yracheta, Joseph; Lazo, Mariana; Vaidya, Dhananjay; Balakrishnan, Poojitha; Gamble, Mary V; Francesconi, Kevin A; Goessler, Walter; Cole, Shelley A; Umans, Jason G; Howard, Barbara V; Navas-Acien, Ana

2018-03-15

Inorganic arsenic exposure is ubiquitous and both exposure and inter-individual differences in its metabolism have been associated with cardiometabolic risk. The association between arsenic exposure and arsenic metabolism with metabolic syndrome and its individual components, however, is relatively unknown. We used poisson regression with robust variance to evaluate the association between baseline arsenic exposure (urine arsenic levels) and metabolism (relative percentage of arsenic species over their sum) with incident metabolic syndrome and its individual components (elevated waist circumference, elevated triglycerides, reduced HDL, hypertension, elevated fasting plasma glucose) in 1,047 participants from the Strong Heart Family Study, a prospective family-based cohort in American Indian communities (baseline visits in 1998-1999 and 2001-2003, follow-up visits in 2001-2003 and 2006-2009). 32% of participants developed metabolic syndrome over follow-up. An IQR increase in arsenic exposure was associated with 1.19 (95% CI: 1.01, 1.41) greater risk for elevated fasting plasma glucose but not with other individual components or overall metabolic syndrome. Arsenic metabolism, specifically lower MMA% and higher DMA% was associated with higher risk of overall metabolic syndrome and elevated waist circumference, but not with any other component. These findings support there is a contrasting and independent association between arsenic exposure and arsenic metabolism with metabolic outcomes which may contribute to overall diabetes risk.

The die is cast - Arsenic exposure in early life and disease susceptibility

Science.gov (United States)

Abstract Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for development and progression of disease in bo...

Fluoxetine treatment ameliorates depression induced by perinatal arsenic exposure via a neurogenic mechanism

Science.gov (United States)

Tyler, Christina R.; Solomon, Benjamin R.; Ulibarri, Adam L.; Allan, Andrea M.

2014-01-01

Several epidemiological studies have reported an association between arsenic exposure and increased rates of psychiatric disorders, including depression, in exposed populations. We have previously demonstrated that developmental exposure to low amounts of arsenic induces depression in adulthood along with several morphological and molecular aberrations, particularly associated with the hippocampus and the hypothalamic–pituitary–adrenal (HPA) axis. The extent and potential reversibility of this toxin-induced damage has not been characterized to date. In this study, we assessed the effects of fluoxetine, a selective serotonin reuptake inhibitor antidepressant, on adult animals exposed to arsenic during development. Perinatal arsenic exposure (PAE) induced depressive-like symptoms in a mild learned helplessness task and in the forced swim task after acute exposure to a predator odor (2,4,5-trimethylthiazoline, TMT). Chronic fluoxetine treatment prevented these behaviors in both tasks in arsenic-exposed animals and ameliorated arsenic-induced blunted stress responses, as measured by corticosterone (CORT) levels before and after TMT exposure. Morphologically, chronic fluoxetine treatment reversed deficits in adult hippocampal neurogenesis (AHN) after PAE, specifically differentiation and survival of neural progenitor cells. Protein expression of BDNF, CREB, the glucocorticoid receptor (GR), and HDAC2 was significantly increased in the dentate gyrus of arsenic animals after fluoxetine treatment. This study demonstrates that damage induced by perinatal arsenic exposure is reversible with chronic fluoxetine treatment resulting in restored resiliency to depression via a neurogenic mechanism. PMID:24952232

Transcriptional changes associated with reduced spontaneous liver tumor incidence in mice chronically exposed to high dose arsenic

International Nuclear Information System (INIS)

Nelson, Gail M.; Ahlborn, Gene J.; Allen, James W.; Ren, Hongzu; Corton, J. Christopher; Waalkes, Michael P.; Kitchin, Kirk T.; Diwan, Bhalchandra A.; Knapp, Geremy; Delker, Don A.

2009-01-01

Exposure of male C3H mice in utero (from gestational days 8-18) to 85 ppm sodium arsenite via the dams' drinking water has previously been shown to increase liver tumor incidence by 2 years of age. However, in our companion study (Ahlborn et al., 2009), continuous exposure to 85 ppm sodium arsenic (from gestational day 8 to postnatal day 365) did not result in increased tumor incidence, but rather in a significant reduction (0% tumor incidence). The purpose of the present study was to examine the gene expression responses that may lead to the apparent protective effect of continuous arsenic exposure. Genes in many functional categories including cellular growth and proliferation, gene expression, cell death, oxidative stress, protein ubiquitination, and mitochondrial dysfunction were altered by continuous arsenic treatment. Many of these genes are known to be involved in liver cancer. One such gene associated with rodent hepatocarcinogenesis, Scd1, encodes stearoyl-CoA desaturase and was down-regulated by continuous arsenic treatment. An overlap between the genes in our study affected by continuous arsenic exposure and those from the literature affected by long-term caloric restriction suggests that reduction in the spontaneous tumor incidence under both conditions may involve similar gene pathways such as fatty acid metabolism, apoptosis, and stress response.

Chronic arsenic exposure increases TGFalpha concentration in bladder urothelial cells of Mexican populations environmentally exposed to inorganic arsenic

International Nuclear Information System (INIS)

Valenzuela, Olga L.; Germolec, Dori R.; Borja-Aburto, Victor H.; Contreras-Ruiz, Jose; Garcia-Vargas, Gonzalo G.; Razo, Luz M. del

2007-01-01

Inorganic arsenic (iAs) is a well-established carcinogen and human exposure has been associated with a variety of cancers including those of skin, lung, and bladder. High expression of transforming growth factor alpha (TGF-α) has associated with local relapses in early stages of urinary bladder cancer. iAs exposures are at least in part determined by the rate of formation and composition of iAs metabolites (MAs III , MAs V , DMAs III , DMAs V ). This study examines the relationship between TGF-α concentration in exfoliated bladder urothelial cells (BUC) separated from urine and urinary arsenic species in 72 resident women (18-51 years old) from areas exposed to different concentrations of iAs in drinking water (2-378 ppb) in central Mexico. Urinary arsenic species, including trivalent methylated metabolites were measured by hydride generation atomic absorption spectrometry method. The concentration of TGF-α in BUC was measured using an ELISA assay. Results show a statistically significant positive correlation between TGF-α concentration in BUC and each of the six arsenic species present in urine. The multivariate linear regression analyses show that the increment of TGF-α levels in BUC was importantly associated with the presence of arsenic species after adjusting by age, and presence of urinary infection. People from areas with high arsenic exposure had a significantly higher TGF-α concentration in BUC than people from areas of low arsenic exposure (128.8 vs. 64.4 pg/mg protein; p < 0.05). Notably, exfoliated cells isolated from individuals with skin lesions contained significantly greater amount of TGF-α than cells from individuals without skin lesions: 157.7 vs. 64.9 pg/mg protein (p = 0.003). These results suggest that TGF-α in exfoliated BUC may serve as a susceptibility marker of adverse health effects on epithelial tissue in arsenic-endemic areas

In utero exposure to benzene increases embryonic c-Myb and Pim-1 protein levels in CD-1 mice

International Nuclear Information System (INIS)

Wan, Joanne; Winn, Louise M.

2008-01-01

Benzene is a known human leukemogen, but its role as an in utero leukemogen remains controversial. Epidemiological studies have correlated parental exposure to benzene with an increased incidence of childhood leukemias. We hypothesize that in utero exposure to benzene may cause leukemogenesis by affecting the embryonic c-Myb/Pim-1 signaling pathway and that this is mediated by oxidative stress. To investigate this hypothesis, pregnant CD-1 mice were treated with either 800 mg/kg of benzene or corn oil (i.p.) on days 10 and 11 of gestation and in some cases pretreated with 25 kU/kg of PEG-catalase. Phosphorylated and total embryonic c-Myb and Pim-1 protein levels were assessed using Western blotting and maternal and embryonic oxidative stress were assessed by measuring reduced to oxidized glutathione ratios. Our results show increased oxidative stress at 4 and 24 h after exposure, increased phosphorylated Pim-1 protein levels 4 h after benzene exposure, and increased Pim-1 levels at 24 and 48 h after benzene exposure. Embryonic c-Myb levels were elevated at 24 h after exposure. PEG-catalase pretreatment prevented benzene-mediated increases in embryonic c-Myb and Pim-1 protein levels, and benzene-induced oxidative stress. These results support a role for ROS in c-Myb and Pim-1 alterations after in utero benzene exposure

Combinatorial effects of zinc deficiency and arsenic exposure on zebrafish (Danio rerio development.

Directory of Open Access Journals (Sweden)

Laura M Beaver

Full Text Available Zinc deficiency and chronic low level exposures to inorganic arsenic in drinking water are both significant public health concerns that affect millions of people including pregnant women. These two conditions can co-exist in the human population but little is known about their interaction, and in particular, whether zinc deficiency sensitizes individuals to arsenic exposure and toxicity, especially during critical windows of development. To address this, we utilized the Danio rerio (zebrafish model to test the hypothesis that parental zinc deficiency sensitizes the developing embryo to low-concentration arsenic toxicity, leading to altered developmental outcomes. Adult zebrafish were fed defined zinc deficient and zinc adequate diets and were spawned resulting in zinc adequate and zinc deficient embryos. The embryos were treated with environmentally relevant concentrations of 0, 50, and 500 ppb arsenic. Arsenic exposure significantly reduced the amount of zinc in the developing embryo by ~7%. The combination of zinc deficiency and low-level arsenic exposures did not sensitize the developing embryo to increased developmental malformations or mortality. The combination did cause a 40% decline in physical activity of the embryos, and this decline was significantly greater than what was observed with zinc deficiency or arsenic exposure alone. Significant changes in RNA expression of genes that regulate zinc homeostasis, response to oxidative stress and insulin production (including zip1, znt7, nrf2, ogg1, pax4, and insa were found in zinc deficient, or zinc deficiency and arsenic exposed embryos. Overall, the data suggests that the combination of zinc deficiency and arsenic exposure has harmful effects on the developing embryo and may increase the risk for developing chronic diseases like diabetes.

Association of arsenic exposure with lung cancer incidence rates in the United States.

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Joseph J Putila

Full Text Available Although strong exposure to arsenic has been shown to be carcinogenic, its contribution to lung cancer incidence in the United States is not well characterized. We sought to determine if the low-level exposures to arsenic seen in the U.S. are associated with lung cancer incidence after controlling for possible confounders, and to assess the interaction with smoking behavior.Measurements of arsenic stream sediment and soil concentration obtained from the USGS National Geochemical Survey were combined, respectively, with 2008 BRFSS estimates on smoking prevalence and 2000 U.S. Census county level income to determine the effects of these factors on lung cancer incidence, as estimated from respective state-wide cancer registries and the SEER database. Poisson regression was used to determine the association between each variable and age-adjusted county-level lung cancer incidence. ANOVA was used to assess interaction effects between covariates.Sediment levels of arsenic were significantly associated with an increase in incident cases of lung cancer (P<0.0001. These effects persisted after controlling for smoking and income (P<0.0001. Across the U.S., exposure to arsenic may contribute to up to 5,297 lung cancer cases per year. There was also a significant interaction between arsenic exposure levels and smoking prevalence (P<0.05.Arsenic was significantly associated with lung cancer incidence rates in the U.S. after controlling for smoking and income, indicating that low-level exposure to arsenic is responsible for excess cancer cases in many parts of the U.S. Elevated county smoking prevalence strengthened the association between arsenic exposure and lung cancer incidence rate, an effect previously unseen on a population level.

Cancer excess after arsenic exposure from contaminated milk powder

DEFF Research Database (Denmark)

Yorifuji, Takashi; Tsuda, Toshihide; Doi, Hiroyuki

2011-01-01

Long-term exposure to inorganic arsenic is related to increased risk of cancer in the lung, skin, bladder, and, possibly, other sites. However, little is known about the consequences of developmental exposures in regard to cancer risk. During early summer in 1955, mass arsenic poisoning of infant...... occurred in the western part of Japan because of contaminated milk powder. Okayama Prefecture was most severely affected. We examined whether the affected birth cohorts in this prefecture experienced increased cancer mortality....

Inorganic arsenic exposure and type 2 diabetes mellitus in Mexico

International Nuclear Information System (INIS)

Coronado-Gonzalez, Jose Antonio; Razo, Luz Maria del; Garcia-Vargas, Gonzalo; Sanmiguel-Salazar, Francisca; Escobedo-de la Pena, Jorge

2007-01-01

Inorganic arsenic exposure in drinking water has been recently related to diabetes mellitus. To evaluate this relationship the authors conducted in 2003, a case-control study in an arseniasis-endemic region from Coahuila, a northern state of Mexico with a high incidence of diabetes. The present analysis includes 200 cases and 200 controls. Cases were obtained from a previous cross-sectional study conducted in that region. Diagnosis of diabetes was established following the American Diabetes Association criteria, with two fasting glucose values ≥126 mg/100 ml (≥7.0 mmol/l) or a history of diabetes treated with insulin or oral hypoglycemic agents. The next subject studied, subsequent to the identification of a case in the cross-sectional study was taken as control. Inorganic arsenic exposure was measured through total arsenic concentrations in urine, measured by hydride-generation atomic absorption spectrophotometry. Subjects with intermediate total arsenic concentration in urine (63.5-104 μg/g creatinine) had two-fold higher risk of having diabetes (odds ratio=2.16; 95% confidence interval: 1.23, 3.79), but the risk was almost three times greater in subjects with higher concentrations of total arsenic in urine (odds ratio=2.84; 95% confidence interval: 1.64, 4.92). This data provides additional evidence that inorganic arsenic exposure may be diabetogenic

Influence of prenatal arsenic exposure and newborn sex on global methylation of cord blood DNA.

Directory of Open Access Journals (Sweden)

J Richard Pilsner

Full Text Available BACKGROUND: An emerging body of evidence indicates that early-life arsenic (As exposure may influence the trajectory of health outcomes later in life. However, the mechanisms underlying these observations are unknown. OBJECTIVE: The objective of this study was to investigate the influence of prenatal As exposure on global methylation of cord blood DNA in a study of mother/newborn pairs in Matlab, Bangladesh. DESIGN: Maternal and cord blood DNA were available from a convenience sample of 101 mother/newborn pairs. Measures of As exposure included maternal urinary As (uAs, maternal blood As (mbAs and cord blood As (cbAs. Several measures of global DNA methylation were assessed, including the [3H]-methyl-incorporation assay and three Pyrosequencing assays: Alu, LINE-1 and LUMA. RESULTS: In the total sample, increasing quartiles of maternal uAs were associated with an increase in covariate-adjusted means of newborn global DNA methylation as measured by the [3H]-methyl-incorporation assay (quartile 1 (Q1 and Q2 vs. Q4; p = 0.06 and 0.04, respectively. Sex-specific linear regression analyses, while not reaching significance level of 0.05, indicated that the associations between As exposures and Alu, LINE-1 and LUMA were positive among male newborns (N = 58 but negative among female newborns (N = 43; tests for sex differences were borderline significant for the association of cbAs and mbAs with Alu (p = 0.05 and 0.09, respectively and for the association between maternal uAs and LINE-1 (p = 0.07. Sex-specific correlations between maternal urinary creatinine and newborn methyl-incorporation, Alu and LINE-1 were also evident (p<0.05. CONCLUSIONS: These results suggest that prenatal As exposure is associated with global DNA methylation in cord blood DNA, possibly in a sex-specific manner. Arsenic-induced epigenetic modifications in utero may potentially influence disease outcomes later in life. Additional studies are needed to confirm

The use of docosahexaenoic acid supplementation to ameliorate the hyperactivity of rat pups induced by in utero ethanol exposure

OpenAIRE

Furuya, Hiroyuki; Aikawa, Hiroyuki; Yoshida, Takahiko; Okazaki, Isao

2000-01-01

It has been demonstrated thatin utero ethanol (EtOH) exposure induces hyperactive behavior and learning disturbances in offspring. In order to investigate the effects of docosahexaenoic acid (DHA) on these neurobehavioral dysfunctions of rat pups induced byin utero EtOH exposure, pregnant Wistar rats were divided into four treatment groups depending on the type of oil added to the diet and drinking water as follows; (a) 5% safflower oil with tap water (TW/n-6), (b) 3% safflower oil and 2% DHA...

Arsenic exposure disrupts epigenetic regulation of SIRT1 in human keratinocytes

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Herbert, Katharine J. [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia); Holloway, Adele [Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000 (Australia); Cook, Anthony L. [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia); Chin, Suyin P. [Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000 (Australia); Snow, Elizabeth T., E-mail: elizabeth.snow@utas.edu.au [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia)

2014-11-15

Arsenic is an environmental toxin which increases skin cancer risk for exposed populations worldwide; however the underlying biomolecular mechanism for arsenic-induced carcinogenesis is complex and poorly defined. Recent investigations show that histone deacetylase and DNA methyltransferase activity is impaired, and epigenetic patterns of gene regulation are consistently altered in cancers associated with arsenic exposure. Expression of the histone deacetylase SIRT1 is altered in solid tumours and haematological malignancies; however its role in arsenic-induced pathology is unknown. In this study we investigated the effect of arsenic on epigenetic regulation of SIRT1 and its targeting microRNA, miR-34a in primary human keratinocytes. Acetylation of histone H4 at lysine 16 (H4K16) increased in keratinocytes exposed to 0.5 μM arsenite [As(III)]; and this was associated with chromatin remodelling at the miR-34a promoter. Moreover, although SIRT1 protein initially increased in these As(III)-exposed cells, after 24 days expression was not significantly different from untreated controls. Extended exposure to low-dose As(III) (0.5 μM; > 5 weeks) compromised the pattern of CpG methylation at SIRT1 and miR-34a gene promoters, and this was associated with altered expression for both genes. We have found that arsenic alters epigenetic regulation of SIRT1 expression via structural reorganisation of chromatin at the miR-34a gene promoter in the initial 24 h of exposure; and over time, through shifts in miR-34a and SIRT1 gene methylation. Taken together, this investigation demonstrates that arsenic produces cumulative disruptions to epigenetic regulation of miR-34a expression, and this is associated with impaired coordination of SIRT1 functional activity. - Highlights: • Submicromolar arsenic concentrations disrupt SIRT1 activity and expression in human keratinocytes. • Arsenic-induced chromatin remodelling at the miR-34a gene promoter is associated with hyperacetylation

Arsenic exposure disrupts epigenetic regulation of SIRT1 in human keratinocytes

International Nuclear Information System (INIS)

Herbert, Katharine J.; Holloway, Adele; Cook, Anthony L.; Chin, Suyin P.; Snow, Elizabeth T.

2014-01-01

Arsenic is an environmental toxin which increases skin cancer risk for exposed populations worldwide; however the underlying biomolecular mechanism for arsenic-induced carcinogenesis is complex and poorly defined. Recent investigations show that histone deacetylase and DNA methyltransferase activity is impaired, and epigenetic patterns of gene regulation are consistently altered in cancers associated with arsenic exposure. Expression of the histone deacetylase SIRT1 is altered in solid tumours and haematological malignancies; however its role in arsenic-induced pathology is unknown. In this study we investigated the effect of arsenic on epigenetic regulation of SIRT1 and its targeting microRNA, miR-34a in primary human keratinocytes. Acetylation of histone H4 at lysine 16 (H4K16) increased in keratinocytes exposed to 0.5 μM arsenite [As(III)]; and this was associated with chromatin remodelling at the miR-34a promoter. Moreover, although SIRT1 protein initially increased in these As(III)-exposed cells, after 24 days expression was not significantly different from untreated controls. Extended exposure to low-dose As(III) (0.5 μM; > 5 weeks) compromised the pattern of CpG methylation at SIRT1 and miR-34a gene promoters, and this was associated with altered expression for both genes. We have found that arsenic alters epigenetic regulation of SIRT1 expression via structural reorganisation of chromatin at the miR-34a gene promoter in the initial 24 h of exposure; and over time, through shifts in miR-34a and SIRT1 gene methylation. Taken together, this investigation demonstrates that arsenic produces cumulative disruptions to epigenetic regulation of miR-34a expression, and this is associated with impaired coordination of SIRT1 functional activity. - Highlights: • Submicromolar arsenic concentrations disrupt SIRT1 activity and expression in human keratinocytes. • Arsenic-induced chromatin remodelling at the miR-34a gene promoter is associated with hyperacetylation

Chronic exposure to low concentration of arsenic is immunotoxic to fish: Role of head kidney macrophages as biomarkers of arsenic toxicity to Clarias batrachus

International Nuclear Information System (INIS)

Datta, Soma; Ghosh, Debabrata; Saha, Dhira Rani; Bhattacharaya, Shelley; Mazumder, Shibnath

2009-01-01

The present study was aimed at elucidating the effect of chronic low-level arsenic exposure on the head kidney (HK) of Clarias batrachus and at determining the changes in head kidney macrophage (HKM) activity in response to arsenic exposure. Chronic exposure (30 days) to arsenic (As 2 O 3 , 0.50 μM) led to significant increase in arsenic content in the HK accompanied by reduction in both HKM number and head kidney somatic index (HKSI). Arsenic induced HK hypertrophy, reduction in melano-macrophage population and increased hemosiderin accumulation. Transmission electron microscopy of 30 days exposed HKM revealed prominent endoplasmic reticulum, chromatin condensation and loss in structural integrity of nuclear membrane. Head kidney macrophages from exposed fish demonstrated significant levels of superoxide anions but on infection with Aeromonas hydrophila were unable to clear the intracellular bacteria and died. Exposure-challenge experiments with A. hydrophila revealed that chronic exposure to micromolar concentration of arsenic interfered with the phagocytic potential of HKM, helped in intracellular survival of the ingested bacteria inside the HKM inducing significant HKM cytotoxicity. The immunosuppressive effect of arsenic was further evident from the ability of A. hydrophila to colonize and disseminate efficiently in exposed fish. Enzyme linked immunosorbent assay indicated that chronic exposure to arsenic suppressed the production of pro-inflammatory 'IL-1β like' factors from HKM. It is concluded that arsenic even at very low concentration is immunotoxic to fish and the changes observed in HKM may provide a useful early biomarker of low-level xenobiotic exposure

Chronic exposure to low concentration of arsenic is immunotoxic to fish: Role of head kidney macrophages as biomarkers of arsenic toxicity to Clarias batrachus

Energy Technology Data Exchange (ETDEWEB)

Datta, Soma; Ghosh, Debabrata [Immunobiology Laboratory, School of Life Sciences, Visva Bharati University, Santiniketan 731 235 (India); Saha, Dhira Rani [Microscopy Laboratory, National Institute of Cholera and Enteric Diseases, P-33, Scheme XM, C.I.T. Road, Beliaghata, Kolkata 700 010 (India); Bhattacharaya, Shelley [Environmental Toxicology Laboratory, School of Life Sciences, Visva Bharati University, Santiniketan 731 235 (India); Mazumder, Shibnath [Immunobiology Laboratory, School of Life Sciences, Visva Bharati University, Santiniketan 731 235 (India)], E-mail: shibnath1@yahoo.co.in

2009-04-09

The present study was aimed at elucidating the effect of chronic low-level arsenic exposure on the head kidney (HK) of Clarias batrachus and at determining the changes in head kidney macrophage (HKM) activity in response to arsenic exposure. Chronic exposure (30 days) to arsenic (As{sub 2}O{sub 3}, 0.50 {mu}M) led to significant increase in arsenic content in the HK accompanied by reduction in both HKM number and head kidney somatic index (HKSI). Arsenic induced HK hypertrophy, reduction in melano-macrophage population and increased hemosiderin accumulation. Transmission electron microscopy of 30 days exposed HKM revealed prominent endoplasmic reticulum, chromatin condensation and loss in structural integrity of nuclear membrane. Head kidney macrophages from exposed fish demonstrated significant levels of superoxide anions but on infection with Aeromonas hydrophila were unable to clear the intracellular bacteria and died. Exposure-challenge experiments with A. hydrophila revealed that chronic exposure to micromolar concentration of arsenic interfered with the phagocytic potential of HKM, helped in intracellular survival of the ingested bacteria inside the HKM inducing significant HKM cytotoxicity. The immunosuppressive effect of arsenic was further evident from the ability of A. hydrophila to colonize and disseminate efficiently in exposed fish. Enzyme linked immunosorbent assay indicated that chronic exposure to arsenic suppressed the production of pro-inflammatory 'IL-1{beta} like' factors from HKM. It is concluded that arsenic even at very low concentration is immunotoxic to fish and the changes observed in HKM may provide a useful early biomarker of low-level xenobiotic exposure.

The Long-Term Economic Impact of In Utero and Postnatal Exposure to Malaria

OpenAIRE

Alan Barreca

2009-01-01

I use an instrumental-variables identification strategy and historical data from the United States to estimate the long-term economic impact of in utero and postnatal exposure to malaria. My research design matches adults in the 1960 Decennial Census to the malaria death rate in their respective state and year of birth. To address potential omitted variables bias and measurement-error bias, I use variation in "malaria-ideal" temperatures to instrument for malaria exposure. My estimates indica...

Exercise Prevents Memory Impairment Induced by Arsenic Exposure in Mice: Implication of Hippocampal BDNF and CREB.

Directory of Open Access Journals (Sweden)

Bao-Fei Sun

Full Text Available High concentrations of arsenic, which can be occasionally found in drinking water, have been recognized as a global health problem. Exposure to arsenic can disrupt spatial memory; however, the underlying mechanism remains unclear. In the present study, we tested whether exercise could interfere with the effect of arsenic exposure on the long-term memory (LTM of object recognition in mice. Arsenic (0, 1, 3, and 10 mg/ kg, i.g. was administered daily for 12 weeks. We found that arsenic at dosages of 1, 3, and 10 mg/kg decreased body weight and increased the arsenic content in the brain. The object recognition LTM (tested 24 h after training was disrupted by 3 mg/ kg and 10 mg/ kg, but not 1 mg/ kg arsenic exposure. Swimming exercise also prevented LTM impairment induced by 3 mg/ kg, but not with 10 mg/ kg, of arsenic exposure. The expression of brain-derived neurotrophic factor (BDNF and phosphorylated cAMP-response element binding protein (pCREB in the CA1 and dentate gyrus areas (DG of the dorsal hippocampus were decreased by 3 mg/ kg and 10 mg/ kg, but not by 1 mg/ kg, of arsenic exposure. The decrease in BDNF and pCREB in the CA1 and DG induced by 3 mg/ kg, but not 10 mg/ kg, of arsenic exposure were prevented by swimming exercise. Arsenic exposure did not affect the total CREB expression in the CA1 or DG. Taken together, these results indicated that swimming exercise prevented the impairment of object recognition LTM induced by arsenic exposure, which may be mediated by BDNF and CREB in the dorsal hippocampus.

Association between arsenic exposure and plasma cholinesterase activity: a population based study in Bangladesh

Directory of Open Access Journals (Sweden)

Karim Md Rezaul

2010-07-01

Full Text Available Abstract Background Arsenic is a potent pollutant that has caused an environmental catastrophe in certain parts of the world including Bangladesh where millions of people are presently at risk due to drinking water contaminated by arsenic. Chronic arsenic exposure has been scientifically shown as a cause for liver damage, cancers, neurological disorders and several other ailments. The relationship between plasma cholinesterase (PChE activity and arsenic exposure has not yet been clearly documented. However, decreased PChE activity has been found in patients suffering liver dysfunction, heart attack, cancer metastasis and neurotoxicity. Therefore, in this study, we evaluated the PChE activity in individuals exposed to arsenic via drinking water in Bangladesh. Methods A total of 141 Bangladeshi residents living in arsenic endemic areas with the mean arsenic exposure of 14.10 ± 3.27 years were selected as study subjects and split into tertile groups based on three water arsenic concentrations: low ( 265 μg/L. Study subjects were further sub-divided into two groups (≤50 μg/L and > 50 μg/L based on the recommended upper limit of water arsenic concentration (50 μg/L in Bangladesh. Blood samples were collected from the study subjects by venipuncture and arsenic concentrations in drinking water, hair and nail samples were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS. PChE activity was assayed by spectrophotometer. Results Arsenic concentrations in hair and nails were positively correlated with the arsenic levels in drinking water. Significant decreases in PChE activity were observed with increasing concentrations of arsenic in water, hair and nails. The average levels of PChE activity in low, medium and high arsenic exposure groups were also significantly different between each group. Lower levels of PChE activity were also observed in the > 50 μg/L group compared to the ≤50 μg/L group. Moreover, PChE activity was

Risk of Erectile Dysfunction Induced by Arsenic Exposure through Well Water Consumption in Taiwan

Science.gov (United States)

Hsieh, Fang-I; Hwang, Ti-Sheng; Hsieh, Yi-Chen; Lo, Hsiu-Chiung; Su, Chien-Tien; Hsu, Hui-Shing; Chiou, Hung-Yi; Chen, Chien-Jen

2008-01-01

Background Erectile dysfunction (ED) has a profound impact on the quality of life of many men. Many risk factors are associated with ED, such as aging, sex hormone levels, hypertension, cardiovascular diseases, and diabetes mellitus. Arsenic exposure could damage peripheral vessels and increase the risk of cardiovascular disease. However, the relationship between arsenic exposure and ED has seldom been evaluated. Objectives In this study we aimed to investigate whether exposure to arsenic enhances the risk of ED. Methods We recruited 177 males ≥ 50 years of age through health examinations conducted in three hospitals in Taiwan. We used a questionnaire (International Index of Erectile Function-5) to measure the level of erectile function. Sex hormones, including total testosterone and sex hormone–binding globulin, were determined by radioimmunoassay. We used another standardized questionnaire to collect background and behavioral information (e.g., cigarette smoking; alcohol, tea, or coffee drinking; and physical activity). Results The prevalence of ED was greater in the arsenic-endemic area (83.3%) than in the non–arsenic-endemic area (66.7%). Subjects with arsenic exposure > 50 ppb had a significantly higher risk of developing ED than those with exposure ≤ 50 ppb, after adjusting for age, cigarette smoking, diabetes mellitus, hypertension, and cardiovascular disease [odds ratio (OR) = 3.4]. Results also showed that the risk of developing severe ED was drastically enhanced by arsenic exposure (OR = 7.5), after adjusting for free testosterone and traditional risk factors of ED. Conclusions Results suggested that chronic arsenic exposure has a negative impact on erectile function. PMID:18414639

[Study of relationship between arsenic methylation and skin lesion in a population with long-term high arsenic exposure].

Science.gov (United States)

Su, Liqin; Cheng, Yibin; Lin, Shaobin; Wu, Chuanye

2007-05-01

To investigate the difference of arsenic metabolism in populations with long-term high arsenic exposure and explore the relationship between arsenic metabolism diversity and skin lesion. 327 residents in an arsenic polluted village were voluntarily enrolled in this study. Questionnaire survey and medical examination were carried out to learn basic information and detect skin lesions. Urinary inorganic and methylated arsenic were speciated by high performance liquid chromatography combined with hydride-generation atomic fluorescence spectrometry. Total arsenic concentration in hair was determined with DDC-Ag method. Hair arsenic content of studied polutions was generally high, but no significant difference were found among the studied four groups. MMA and DMA concentration in urine increased with studied polution age, and were positively related with skin lesion grade. The relative proportion of MMA in serious skin lesion group was significantly higher than in other 3 groups, while DMA/MMA ratio was significantly lower than control and mild group. The relative proportion of MMA was positively related with skin lesion grade, DMA/ MMA ratio was negatively related with skin lesion grade. Males could have higher arsenic cumulation and lower methylation capacity than those of females. The population of above 40 years old may have higher methylation capacity than those of adults below 40yeas old. Smokers and drinkers seemed lower methylation capacity than those of non-smokers and non-drinkers respectively. The methylation of arsenic could affect by several factors, including age gender, smoking and drinking. Arsenic methylation copacity mey be associated with skin lesion induced by arsenic exposure.

Cadmium and lung cancer mortality accounting for simultaneous arsenic exposure.

Science.gov (United States)

Park, Robert M; Stayner, Leslie T; Petersen, Martin R; Finley-Couch, Melissa; Hornung, Richard; Rice, Carol

2012-05-01

Prior investigations identified an association between airborne cadmium and lung cancer but questions remain regarding confounding by arsenic, a well-established lung carcinogen. A cadmium smelter population exhibiting excess lung cancer was re-analysed using a retrospective exposure assessment for arsenic (As), updated mortality (1940-2002), a revised cadmium (Cd) exposure matrix and improved work history information. Cumulative exposure metrics for both cadmium and arsenic were strongly associated making estimation of their independent effects difficult. Standardised mortality ratios (SMRs) were modelled with Poisson regression with the contribution of arsenic to lung cancer risk constrained by exposure-response estimates previously reported. The results demonstrate (1) a statistically significant effect of Cd independent of As (SMR=3.2 for 10 mg-year/m(3) Cd, p=0.012), (2) a substantial healthy worker effect for lung cancer (for unexposed workers, SMR=0.69) and (3) a large deficit in lung cancer mortality among Hispanic workers (SMR=0.27, p=0.009), known to have low lung cancer rates. A supralinear dose-rate effect was observed (contribution to risk with increasing exposure intensity has declining positive slope). Lung cancer mortality was somewhat better predicted using a cadmium burden metric with a half-life of about 20-25 years. These findings support an independent effect for cadmium in risk of lung cancer mortality. 1/1000 excess lifetime risk of lung cancer death is predicted from an airborne exposure of about 2.4 μg/m(3) Cd.

Arsenic Exposure and Type 2 Diabetes: MicroRNAs as Mechanistic Links?

OpenAIRE

Beck, Rowan; Styblo, Miroslav; Sethupathy, Praveen

2017-01-01

Purpose of Review The goal of this review is to delineate the following: (1) the primary means of inorganic arsenic (iAs) exposure for human populations, (2) the adverse public health outcomes associated with chronic iAs exposure, (3) the pathophysiological connection between arsenic and type 2 diabetes (T2D), and (4) the incipient evidence for microRNAs as candidate mechanistic links between iAs exposure and T2D. Recent Findings Exposure to iAs in animal models has been associated with the d...

Perturbations in immune responses induced by concurrent subchronic exposure to arsenic and endosulfan

International Nuclear Information System (INIS)

Aggarwal, Manoj; Naraharisetti, Suresh Babu; Dandapat, S.; Degen, G.H.; Malik, J.K.

2008-01-01

The metalloid arsenic and the chlorinated insecticide endosulfan are common environmental contaminants. Humans, animals, and birds are exposed to these chemicals through water and food. Although health effects due to either arsenic or endosulfan exposure are documented, the toxicological impact of co-exposure to these environmental pollutants is unpredictable and unknown. The present study was undertaken to assess whether concurrent exposure to arsenic and endosulfan induces significant alterations in immunological functions. Day-old chicks were exposed to 3.7 ppm of arsenic via drinking water and to 30 ppm of endosulfan-mixed feed either individually or concurrently for up to 60 days. All the chicks were vaccinated with Ranikhet disease virus (F-strain; RD-F) on days 1 and 30. During the course of study and at term, parameters of cellular and humoral immunity were determined. None of the treatments altered the absolute body weight or body weight gain, except arsenic significantly reduced weight gain on day 60. Absolute, but not the relative, weights of spleen, thymus and bursa of Fabricius were significantly reduced in all the treatment groups. The metalloid and insecticide combination significantly depressed the ability of peripheral blood and splenic lymphocytes to proliferate in response to antigen RD-F and mitogen Con A. The delayed type hypersensitivity response to 2,4-dinitro-1-chlorobenzene or to PHA-P was also significantly decreased. Nitric oxide production by RD-F or lipopolysaccharide-stimulated peripheral blood and splenic mononuclear cells was significantly suppressed following concurrent exposure to arsenic and endosulfan. Furthermore, the combined exposure also decreased the antibody response to RD-F. The suppression of cellular and humoral immune responses was also evident following administration of individual compounds, and it was not exacerbated following concurrent exposure. To our knowledge, this is the first report describing the suppression

The Long-Term Economic Impact of in Utero and Postnatal Exposure to Malaria

Science.gov (United States)

Barreca, Alan I.

2010-01-01

I use an instrumental-variables identification strategy and historical data from the United States to estimate the long-term economic impact of in utero and postnatal exposure to malaria. My research design matches adults in the 1960 Decennial Census to the malaria death rate in their respective state and year of birth. To address potential…

Association of hypothyroidism with low-level arsenic exposure in rural West Texas

International Nuclear Information System (INIS)

Gong, Gordon; Basom, Janet; Mattevada, Sravan; Onger, Frederick

2015-01-01

It has been reported recently that a higher airborne arsenic level was correlated with higher urinary arsenic concentration and lower serum thyroxin level among urban policemen and rural highway workmen in Italy. The current study was to determine whether exposure to low-level arsenic groundwater (2–22 µg/L) is associated with hypothyroidism among 723 participants (118 male and 267 female Hispanics; 108 male and 230 female non-Hispanic whites, NHW) living in rural West Texas counties. Arsenic and iodine levels in their groundwater used for drinking and or cooking were estimated by the inverse distance weighted (IDW) interpolation technique. Groundwater arsenic was ≥8 µg/L in 36% of the subjects' wells while iodine concentration was <1 µg/L in 91% of their wells. Logistic regression analysis showed that arsenic in groundwater ≥8 µg/L and cumulative arsenic exposure (groundwater arsenic concentration multiplied by the number of years living in the current address) but not groundwater iodine concentration were significant predictors for hypothyroidism among Hispanics (p<0.05) but not NHW after adjusting for covariates such as age, gender, annual household income and health insurance coverage. The ethnic difference may be due to a marginally higher percentage of Hispanics (p=0.0622) who lived in areas with groundwater arsenic ≥8 µg/L compared with NHW. The prevalence of hypothyroidism was significantly higher in Hispanics or NHW of this rural cohort than the national prevalence. Measures should be taken to reduce arsenic in drinking water in order to prevent hypothyroidism in rural areas. - Highlights: • We determined if arsenic exposure is associated with hypothyroidism in rural Texas. • Groundwater arsenic level is associated with hypothyroidism among Hispanics only. • The rate of hypothyroidism in rural Texas was higher than the US general population

Association of hypothyroidism with low-level arsenic exposure in rural West Texas

Energy Technology Data Exchange (ETDEWEB)

Gong, Gordon, E-mail: gordon.gong@ttuhsc.edu [F. Marie Hall Institute for Rural and Community Health, Texas Tech University Health Sciences Center, Lubbock, TX (United States); Basom, Janet [F. Marie Hall Institute for Rural and Community Health, Texas Tech University Health Sciences Center, Lubbock, TX (United States); Department of Family and Community Medicine, Texas Tech University Health Sciences Center, Lubbock, TX (United States); Mattevada, Sravan [Department of Internal Medicine, University of North Texas Health Science Center, Fort Worth, TX (United States); Onger, Frederick [Department of Family and Community Medicine, Texas Tech University Health Sciences Center, Lubbock, TX (United States)

2015-04-15

It has been reported recently that a higher airborne arsenic level was correlated with higher urinary arsenic concentration and lower serum thyroxin level among urban policemen and rural highway workmen in Italy. The current study was to determine whether exposure to low-level arsenic groundwater (2–22 µg/L) is associated with hypothyroidism among 723 participants (118 male and 267 female Hispanics; 108 male and 230 female non-Hispanic whites, NHW) living in rural West Texas counties. Arsenic and iodine levels in their groundwater used for drinking and or cooking were estimated by the inverse distance weighted (IDW) interpolation technique. Groundwater arsenic was ≥8 µg/L in 36% of the subjects' wells while iodine concentration was <1 µg/L in 91% of their wells. Logistic regression analysis showed that arsenic in groundwater ≥8 µg/L and cumulative arsenic exposure (groundwater arsenic concentration multiplied by the number of years living in the current address) but not groundwater iodine concentration were significant predictors for hypothyroidism among Hispanics (p<0.05) but not NHW after adjusting for covariates such as age, gender, annual household income and health insurance coverage. The ethnic difference may be due to a marginally higher percentage of Hispanics (p=0.0622) who lived in areas with groundwater arsenic ≥8 µg/L compared with NHW. The prevalence of hypothyroidism was significantly higher in Hispanics or NHW of this rural cohort than the national prevalence. Measures should be taken to reduce arsenic in drinking water in order to prevent hypothyroidism in rural areas. - Highlights: • We determined if arsenic exposure is associated with hypothyroidism in rural Texas. • Groundwater arsenic level is associated with hypothyroidism among Hispanics only. • The rate of hypothyroidism in rural Texas was higher than the US general population.

Biomarkers of exposure, effect, and susceptibility of arsenic-induced health hazards in Taiwan

International Nuclear Information System (INIS)

Chen, C.-J.; Hsu, L.-I; Wang, C.-H.

2005-01-01

Long-term exposure to inorganic arsenic from drinking water has been documented to induce cancers and vascular diseases in a dose-response relationship. A series of molecular environmental epidemiological studies have been carried out to elucidate biomarkers of exposure, effect, and susceptibility for arsenic-related health hazards in Taiwan. Arsenic levels in urine, hair, and nail are biomarkers for short-term (<1 year) internal dose, skin hyperpigmentation and palmoplantar hyperkeratosis are for long-term (many years) internal dose, and percentage of monomethylarsonic acid in total metabolites of inorganic arsenic in urine may be considered as an exposure marker for biologically effective dose. The biomarkers of early biological effects of ingested inorganic arsenic included blood levels of reactive oxidants and anti-oxidant capacity, genetic expression of inflammatory molecules, as well as cytogenetic changes including sister chromatid exchange, micronuclei, and chromosome aberrations of peripheral lymphocytes. Both mutation type and hot spots of p53 gene were significantly different in arsenic-induced and non-arsenic-induced TCCs. The frequency of chromosomal imbalances analyzed by comparative genomic hybridization and the frequency of loss of heterozygosity were significantly higher in arsenic-induced TCC than non-arsenic-induced TCC at specific sites. Biomarkers of susceptibility to arsenic-induced health hazards included genetic polymorphisms of enzymes involved in xenobiotic metabolism, DNA repair, and oxidative stress, as well as serum level of carotenoids. Gene-gene and gene-environment interactions are involved in arsenic-induced health hazards through toxicological mechanisms including genomic instability and oxidative stress

Comparative proteomic analysis reveals heart toxicity induced by chronic arsenic exposure in rats

International Nuclear Information System (INIS)

Huang, Qingyu; Xi, Guochen; Alamdar, Ambreen; Zhang, Jie; Shen, Heqing

2017-01-01

Arsenic is a widespread metalloid in the environment, which poses a broad spectrum of adverse effects on human health. However, a global view of arsenic-induced heart toxicity is still lacking, and the underlying molecular mechanisms remain unclear. By performing a comparative quantitative proteomic analysis, the present study aims to investigate the alterations of proteome profile in rat heart after long-term exposure to arsenic. As a result, we found that the abundance of 81 proteins were significantly altered by arsenic treatment (35 up-regulated and 46 down-regulated). Among these, 33 proteins were specifically associated with cardiovascular system development and function, including heart development, heart morphology, cardiac contraction and dilation, and other cardiovascular functions. It is further proposed that the aberrant regulation of 14 proteins induced by arsenic would disturb cardiac contraction and relaxation, impair heart morphogenesis and development, and induce thrombosis in rats, which is mediated by the Akt/p38 MAPK signaling pathway. Overall, these findings will augment our knowledge of the involved mechanisms and develop useful biomarkers for cardiotoxicity induced by environmental arsenic exposure. - Highlights: • Arsenic exposure has been associated with a number of adverse health effects. • The molecular mechanisms involved in arsenic-induced cardiotoxicity remain unclear. • Differential proteins were identified in arsenic-exposed rat heart by proteomics. • Arsenic induces heart toxicity through the Akt/p38 MAPK signaling pathway. - Label-free quantitative proteomic analysis of rat heart reveals putative mechanisms and biomarkers for arsenic-induced cardiotoxicity.

Total and inorganic arsenic in fish, seafood and seaweeds--exposure assessment.

Science.gov (United States)

Mania, Monika; Rebeniak, Małgorzata; Szynal, Tomasz; Wojciechowska-Mazurek, Maria; Starska, Krystyna; Ledzion, Ewa; Postupolski, Jacek

2015-01-01

According to the European Food Safety Authority (EFSA), fish, seafood and seaweeds are foodstuffs that significantly contribute to dietary arsenic intake. With the exception of some algal species, the dominant compounds of arsenic in such food products are the less toxic organic forms. Both the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and EFSA recommend that speciation studies be performed to determine the different chemical forms in which arsenic is present in food due to the differences in their toxicity. Knowing such compositions can thus enable a complete exposure assessment to be made. Determination of total and inorganic arsenic contents in fish, their products, seafood and seaweeds present on the Polish market. This was then followed by an exposure assessment of consumers to inorganic arsenic in these foodstuffs. Total and inorganic arsenic was determined in 55 samples of fish, their products, seafood as well as seaweeds available on the market. The analytical method was hydride generation atomic absorption spectrometry (HGAAS), after dry ashing of samples and reduction of arsenic to arsenic hydride using sodium borohydride. In order to isolate only the inorganic forms of arsenic prior to mineralisation, samples were subjected to concentrated HCl hydrolysis, followed by reduction with hydrobromic acid and hydrazine sulphate after which triple chloroform extractions and triple 1M HCl re-extractions were performed. Exposure of adults was estimated in relation to the Benchmark Dose Lower Confidence Limit (BMDL0.5) as set by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) that resulted in a 0.5% increase in lung cancer (3.0 μg/kg body weight (b.w.) per day). Mean total arsenic content from all investigated fish samples was 0.46 mg/kg (90th percentile 0.94 mg/kg), whilst the inorganic arsenic content never exceeded the detection limit of the analytical method used (0.025 mg/kg). In fish products, mean total arsenic concentration was

In utero exposure to persistent organochlorine pollutants and reproductive health in the human male

DEFF Research Database (Denmark)

Vested, Anne; Ramlau-Hansen, Cecilia H; Olsen, Sjurdur F

2014-01-01

median (range) exposure levels of ΣPCB, ΣDL-PCB, and p,p'-DDE were 10.0 (2.1-35.0) pmol/ml, 0.8 (0.2-2.7) pmol/ml, and 8.0 (0.7-55.3) pmol/ml, respectively, reflecting typical background exposure levels in the late 1980s in Denmark. Results suggested that in utero exposure to ΣPCB, ΣDL-PCB, and p...

Arsenic exposure in pregnant mice disrupts placental vasculogenesis and causes spontaneous abortion.

Science.gov (United States)

He, Wenjie; Greenwell, Robert J; Brooks, Diane M; Calderón-Garcidueñas, Lilian; Beall, Howard D; Coffin, J Douglas

2007-09-01

Arsenic is an abundant toxicant in ground water and soil around areas with extractive industries. Human epidemiological studies have shown that arsenic exposure is linked to developmental defects and miscarriage. The placenta is known to utilize vasculogenesis to develop its circulation. The hypothesis tested here states the following: arsenic exposure causes placental dysmorphogenesis and defective placental vasculogenesis resulting in placental insufficiency and subsequent spontaneous abortion. To test this hypothesis, pregnant mice were exposed to sodium arsenite (AsIII) through drinking water from conception through weanling stages. Neonatal assessment of birth rates, pup weights, and litter sizes in arsenic exposed and control mothers revealed that AsIII-exposed mothers had only 40% the fecundity of controls. Preterm analysis at E12.5 revealed a loss of fecundity at E12.5 from either 20 ppm or greater exposures to AsIII. There was no loss of fecundity at E7.5 suggesting that spontaneous abortion occurs during placentation. Histomorphometry on E12.5 placentae from arsenic-exposed mice revealed placental dysplasia especially in the vasculature. These results suggest that arsenic toxicity is causative for mammalian spontaneous abortion by virtue of aberrant placental vasculogenesis and placental insufficiency.

X-ray exposure in utero and school performance: a population-based study of X-ray pelvimetry

International Nuclear Information System (INIS)

Nordenskjöld, A.C.; Palme, M.; Kaijser, M.

2015-01-01

Aim: To investigate the association between exposure to ionising radiation from pelvimetric examinations in utero and school performance. Material and methods: This was a population-based cohort study comprising 46,066 children born in the county of Östergötland, Sweden, from 1980 through 1990. Through record linkage between Swedish registers, children exposed in utero to X-ray pelvimetry examination were compared to other children born in the same county during the study period, as well as to their unexposed siblings. Outcome variable was primary school grades, expressed in centiles and calculated through linear regression. Results: In the univariate analysis, children exposed to X-ray pelvimetry in utero had higher school grades compared to unexposed children (point estimate 3 centiles, 95% confidence interval [CI]: 1.5 to 4.6). When sex, mother's education and income, birth order, and birth position were included in the analysis; however, the difference was reduced and the association was no longer statistically significant (PE 1.4, 95% CI: –0.1 to 2.8). Comparing exposed children with their siblings showed no statistical difference in univariate analysis or in multivariate analysis. Conclusion: No suggestion was found of a negative effect on school performance from in utero exposure of diagnostic X-ray pelvimetry. -- Highlights: •Pelvimetric examinations expose fetus to low levels of radiation. •No detectable effect on childrens final primary school grades from pelvimetric examinations. •Pelvimetric examinations is a safe procedure for the fetus regarding shool performance

In utero exposure to antidepressants and the use of drugs for pulmonary diseases in children

NARCIS (Netherlands)

ter Horst, P. G. J.; Bos, H. J.; de Jong-van de Berg, L. T. W.; Wilffert, B.

Purpose The use of antidepressants during pregnancy is common. Some studies suggest an association between in utero exposure to antidepressants and the occurrence of pulmonary diseases like asthma later in life. Serotonin reuptake inhibitors (SSRIs) as well tricyclic antidepressants (TCAs) are

In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats disrupts brain sexual differentiation

International Nuclear Information System (INIS)

Ikeda, Masahiko; Mitsui, Tetsuo; Setani, Kaoru; Tamura, Masashi; Kakeyama, Masaki; Sone, Hideko; Tohyama, Chiharu; Tomita, Takako

2005-01-01

The effects of in utero and lactational exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on brain sexual differentiation were investigated. TCDD was orally administered to pregnant Holtzman rats on gestation day (GD) 15, and the activity of brain aromatase, a key enzyme for sexual differentiation, was measured in offspring on postnatal day (PND) 2. Changes in sexual dimorphisms of saccharin preference and the volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) were examined in adult offspring. In controls, litter means of brain aromatase activity were higher in males than in females. In utero exposure to 200 ng/kg TCDD significantly decreased the sex ratio of aromatase activity (male/female) on PND 2. Offspring were weaned on PND28 and the saccharin test was started on PND84. In controls, saccharin (0.25%) intake (g/kg body weight) was significantly higher in female offspring than in males. In utero exposure to 200 ng/kg TCDD significantly increased saccharin intake in male offspring compared with control males, whereas 800 ng/kg TCDD had no effect. Neither dose of TCDD influenced saccharin intake of female offspring. In controls, SDN-POA volume was significantly greater in males than in females at 14 weeks of age. Exposure to 200 ng/kg TCDD significantly decreased SDN-POA volume in males, whereas 800 ng/kg TCDD had no effect. Neither doses of TCDD influenced the SDN-POA volume in female offspring. These results suggest that in utero and lactational TCDD exposure dose-dependently induces demasculinization in male offspring by inhibiting brain aromatase activity in the hypothalamus-preoptic area during central nervous system development

Association of Low-Moderate Arsenic Exposure and Arsenic Metabolism with Incident Diabetes and Insulin Resistance in the Strong Heart Family Study.

Science.gov (United States)

Grau-Perez, Maria; Kuo, Chin-Chi; Gribble, Matthew O; Balakrishnan, Poojitha; Jones Spratlen, Miranda; Vaidya, Dhananjay; Francesconi, Kevin A; Goessler, Walter; Guallar, Eliseo; Silbergeld, Ellen K; Umans, Jason G; Best, Lyle G; Lee, Elisa T; Howard, Barbara V; Cole, Shelley A; Navas-Acien, Ana

2017-12-20

High arsenic exposure has been related to diabetes, but at low-moderate levels the evidence is mixed. Arsenic metabolism, which is partly genetically controlled and may rely on certain B vitamins, plays a role in arsenic toxicity. We evaluated the prospective association of arsenic exposure and metabolism with type 2 diabetes and insulin resistance. We included 1,838 American Indian men and women free of diabetes (median age, 36 y). Arsenic exposure was assessed as the sum of inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) urine concentrations (ΣAs). Arsenic metabolism was evaluated by the proportions of iAs, MMA, and DMA over their sum (iAs%, MMA%, and DMA%). Homeostasis model assessment for insulin resistance (HOMA2-IR) was measured at baseline and follow-up visits. Incident diabetes was evaluated at follow-up. Median ΣAs, iAs%, MMA%, and DMA% was 4.4 μg/g creatinine, 9.5%, 14.4%, and 75.6%, respectively. Over 10,327 person-years of follow-up, 252 participants developed diabetes. Median HOMA2-IR at baseline was 1.5. The fully adjusted hazard ratio [95% confidence interval (CI)] for incident diabetes per an interquartile range increase in ΣAs was 1.57 (95% CI: 1.18, 2.08) in participants without prediabetes at baseline. Arsenic metabolism was not associated with incident diabetes. ΣAs was positively associated with HOMA2-IR at baseline but negatively with HOMA2-IR at follow-up. Increased MMA% was associated with lower HOMA2-IR when either iAs% or DMA% decreased. The association of arsenic metabolism with HOMA2-IR differed by B-vitamin intake and AS3MT genetics variants. Among participants without baseline prediabetes, arsenic exposure was associated with incident diabetes. Low MMA% was cross-sectional and prospectively associated with higher HOMA2-IR. Research is needed to confirm possible interactions of arsenic metabolism with B vitamins and AS3MT variants on diabetes risk. https://doi.org/10.1289/EHP2566.

Estimating Inorganic Arsenic Exposure from U.S. Rice and Total Water Intakes

OpenAIRE

Mantha, Madhavi; Yeary, Edward; Trent, John; Creed, Patricia A.; Kubachka, Kevin; Hanley, Traci; Shockey, Nohora; Heitkemper, Douglas; Caruso, Joseph; Xue, Jianping; Rice, Glenn; Wymer, Larry; Creed, John T.

2017-01-01

Background: Among nonoccupationally exposed U.S. residents, drinking water and diet are considered primary exposure pathways for inorganic arsenic (iAs). In drinking water, iAs is the primary form of arsenic (As), while dietary As speciation techniques are used to differentiate iAs from less toxic arsenicals in food matrices. Objectives: Our goal was to estimate the distribution of iAs exposure rates from drinking water intakes and rice consumption in the U.S. population and ethnic- and age-b...

Exposure to Ambient Fine Particulate Air Pollution in Utero as a Risk Factor for Child Stunting in Bangladesh.

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Goyal, Nihit; Canning, David

2017-12-23

Pregnant mothers in Bangladesh are exposed to very high and worsening levels of ambient air pollution. Maternal exposure to fine particulate matter has been associated with low birth weight at much lower levels of exposure, leading us to suspect the potentially large effects of air pollution on stunting in children in Bangladesh. We estimate the relationship between exposure to air pollution in utero and child stunting by pooling outcome data from four waves of the nationally representative Bangladesh Demographic and Health Survey conducted between 2004 and 2014, and calculating children's exposure to ambient fine particulate matter in utero using high resolution satellite data. We find significant increases in the relative risk of child stunting, wasting, and underweight with higher levels of in utero exposure to air pollution, after controlling for other factors that have been found to contribute to child anthropometric failure. We estimate the relative risk of stunting in the second, third, and fourth quartiles of exposure as 1.074 (95% confidence interval: 1.014-1.138), 1.150 (95% confidence interval: 1.069-1.237, and 1.132 (95% confidence interval: 1.031-1.243), respectively. Over half of all children in Bangladesh in our sample were exposed to an annual ambient fine particulate matter level in excess of 46 µg/m³; these children had a relative risk of stunting over 1.13 times that of children in the lowest quartile of exposure. Reducing air pollution in Bangladesh could significantly contribute to the Sustainable Development Goal of reducing child stunting.

The broad scope of health effects from chronic arsenic exposure: update on a worldwide public health problem.

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Naujokas, Marisa F; Anderson, Beth; Ahsan, Habibul; Aposhian, H Vasken; Graziano, Joseph H; Thompson, Claudia; Suk, William A

2013-03-01

Concerns for arsenic exposure are not limited to toxic waste sites and massive poisoning events. Chronic exposure continues to be a major public health problem worldwide, affecting hundreds of millions of persons. We reviewed recent information on worldwide concerns for arsenic exposures and public health to heighten awareness of the current scope of arsenic exposure and health outcomes and the importance of reducing exposure, particularly during pregnancy and early life. We synthesized the large body of current research pertaining to arsenic exposure and health outcomes with an emphasis on recent publications. Locations of high arsenic exposure via drinking water span from Bangladesh, Chile, and Taiwan to the United States. The U.S. Environmental Protection Agency maximum contaminant level (MCL) in drinking water is 10 µg/L; however, concentrations of > 3,000 µg/L have been found in wells in the United States. In addition, exposure through diet is of growing concern. Knowledge of the scope of arsenic-associated health effects has broadened; arsenic leaves essentially no bodily system untouched. Arsenic is a known carcinogen associated with skin, lung, bladder, kidney, and liver cancer. Dermatological, developmental, neurological, respiratory, cardiovascular, immunological, and endocrine effects are also evident. Most remarkably, early-life exposure may be related to increased risks for several types of cancer and other diseases during adulthood. These data call for heightened awareness of arsenic-related pathologies in broader contexts than previously perceived. Testing foods and drinking water for arsenic, including individual private wells, should be a top priority to reduce exposure, particularly for pregnant women and children, given the potential for life-long effects of developmental exposure.

CHURCHILL COUNTY, NEVADA ARSENIC STUDY: WATER CONSUMPTION AND EXPOSURE BIOMARKERS

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The US Environmental Protection Agency is required to reevaluate the Maximum Contaminant Level (MCL) for arsenic in 2006. To provide data for reducing uncertainties in assessing health risks associated with exposure to low levels (<200 g/l) of arsenic, a large scale biomarker st...

Human health risks and socio-economic perspectives of arsenic exposure in Bangladesh: A scoping review.

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Rahman, M Azizur; Rahman, A; Khan, M Zaved Kaiser; Renzaho, Andre M N

2018-04-15

Arsenic contamination of drinking water, which can occur naturally or because of human activities such as mining, is the single most important public health issue in Bangladesh. Fifty out of the 64 districts in the country have arsenic concentration of groundwater exceeding 50µgL -1 , the Bangladeshi threshold, affecting 35-77 million people or 21-48% of the total population. Chronic arsenic exposure through drinking water and other dietary sources is an important public health issue worldwide affecting hundreds of millions of people. Consequently, arsenic poisoning has attracted the attention of researchers and has been profiled extensively in the literature. Most of the literature has focused on characterising arsenic poisoning and factors associated with it. However, studies examining the socio-economic aspects of chronic exposure of arsenic through either drinking water or foods remain underexplored. The objectives of this paper are (i) to review arsenic exposure pathways to humans; (ii) to summarise public health impacts of chronic arsenic exposure; and (iii) to examine socio-economic implications and consequences of arsenicosis with a focus on Bangladesh. This scoping review evaluates the contributions of different exposure pathways by analysing arsenic concentrations in dietary and non-dietary sources. The socio-economic consequences of arsenicosis disease in Bangladesh are discussed in this review by considering food habits, nutritional status, socio-economic conditions, and socio-cultural behaviours of the people of the country. The pathways of arsenic exposure in Bangladesh include drinking water, various plant foods and non-dietary sources such as soil. Arsenic affected people are often abandoned by the society, lose their jobs and get divorced and are forced to live a sub-standard life. The fragile public health system in Bangladesh has been burdened by the management of thousands of arsenicosis victims in Bangladesh. Copyright © 2017 Elsevier Inc

Arsenic Exposure, Arsenic Metabolism, and Incident Diabetes in the Strong Heart Study

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Howard, Barbara V.; Umans, Jason G.; Gribble, Matthew O.; Best, Lyle G.; Francesconi, Kevin A.; Goessler, Walter; Lee, Elisa; Guallar, Eliseo; Navas-Acien, Ana

2015-01-01

OBJECTIVE Little is known about arsenic metabolism in diabetes development. We investigated the prospective associations of low-moderate arsenic exposure and arsenic metabolism with diabetes incidence in the Strong Heart Study. RESEARCH DESIGN AND METHODS A total of 1,694 diabetes-free participants aged 45–75 years were recruited in 1989–1991 and followed through 1998–1999. We used the proportions of urine inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) over their sum (expressed as iAs%, MMA%, and DMA%) as the biomarkers of arsenic metabolism. Diabetes was defined as fasting glucose ≥126 mg/dL, 2-h glucose ≥200 mg/dL, self-reported diabetes history, or self-reported use of antidiabetic medications. RESULTS Over 11,263.2 person-years of follow-up, 396 participants developed diabetes. Using the leave-one-out approach to model the dynamics of arsenic metabolism, we found that lower MMA% was associated with higher diabetes incidence. The hazard ratios (95% CI) of diabetes incidence for a 5% increase in MMA% were 0.77 (0.63–0.93) and 0.82 (0.73–0.92) when iAs% and DMA%, respectively, were left out of the model. DMA% was associated with higher diabetes incidence only when MMA% decreased (left out of the model) but not when iAs% decreased. iAs% was also associated with higher diabetes incidence when MMA% decreased. The association between MMA% and diabetes incidence was similar by age, sex, study site, obesity, and urine iAs concentrations. CONCLUSIONS Arsenic metabolism, particularly lower MMA%, was prospectively associated with increased incidence of diabetes. Research is needed to evaluate whether arsenic metabolism is related to diabetes incidence per se or through its close connections with one-carbon metabolism. PMID:25583752

Cardiovascular disease and arsenic exposure in Inner Mongolia, China: a case control study

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BACKGROUND: Millions of people are at risk from the adverse effects of arsenic exposure through drinking water. Increasingly, non-cancer effects such as cardiovascular disease have been associated with drinking water arsenic exposures. However, most studies have been conducted in...

Arsenic exposure at low-to-moderate levels and skin lesions, arsenic metabolism, neurological functions, and biomarkers for respiratory and cardiovascular diseases: Review of recent findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh

International Nuclear Information System (INIS)

Chen Yu; Parvez, Faruque; Gamble, Mary; Islam, Tariqul; Ahmed, Alauddin; Argos, Maria; Graziano, Joseph H.; Ahsan, Habibul

2009-01-01

The contamination of groundwater by arsenic in Bangladesh is a major public health concern affecting 35-75 million people. Although it is evident that high levels (> 300 μg/L) of arsenic exposure from drinking water are related to adverse health outcomes, health effects of arsenic exposure at low-to-moderate levels (10-300 μg/L) are not well understood. We established the Health Effects of Arsenic Longitudinal Study (HEALS) with more than 20,000 men and women in Araihazar, Bangladesh, to prospectively investigate the health effects of arsenic predominately at low-to-moderate levels (0.1 to 864 μg/L, mean 99 μg/L) of arsenic exposure. Findings to date suggest adverse effects of low-to-moderate levels of arsenic exposure on the risk of pre-malignant skin lesions, high blood pressure, neurological dysfunctions, and all-cause and chronic disease mortality. In addition, the data also indicate that the risk of skin lesion due to arsenic exposure is modifiable by nutritional factors, such as folate and selenium status, lifestyle factors, including cigarette smoking and body mass index, and genetic polymorphisms in genes related to arsenic metabolism. The analyses of biomarkers for respiratory and cardiovascular functions support that there may be adverse effects of arsenic on these outcomes and call for confirmation in large studies. A unique strength of the HEALS is the availability of outcome data collected prospectively and data on detailed individual-level arsenic exposure estimated using water, blood and repeated urine samples. Future prospective analyses of clinical endpoints and related host susceptibility will enhance our knowledge on the health effects of low-to-moderate levels of arsenic exposure, elucidate disease mechanisms, and give directions for prevention.

Association between Arsenic Exposure from Drinking Water and Longitudinal Change in Blood Pressure among HEALS Cohort Participants.

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Jiang, Jieying; Liu, Mengling; Parvez, Faruque; Wang, Binhuan; Wu, Fen; Eunus, Mahbub; Bangalore, Sripal; Newman, Jonathan D; Ahmed, Alauddin; Islam, Tariqul; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam; Levy, Diane; Slavkovich, Vesna; Argos, Maria; Scannell Bryan, Molly; Farzan, Shohreh F; Hayes, Richard B; Graziano, Joseph H; Ahsan, Habibul; Chen, Yu

2015-08-01

Cross-sectional studies have shown associations between arsenic exposure and prevalence of high blood pressure; however, studies examining the relationship of arsenic exposure with longitudinal changes in blood pressure are lacking. We evaluated associations of arsenic exposure in relation to longitudinal change in blood pressure in 10,853 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Arsenic was measured in well water and in urine samples at baseline and in urine samples every 2 years after baseline. Mixed-effect models were used to estimate the association of baseline well and urinary creatinine-adjusted arsenic with annual change in blood pressure during follow-up (median, 6.7 years). In the HEALS population, the median water arsenic concentration at baseline was 62 μg/L. Individuals in the highest quartile of baseline water arsenic or urinary creatinine-adjusted arsenic had a greater annual increase in systolic blood pressure compared with those in the reference group (β = 0.48 mmHg/year; 95% CI: 0.35, 0.61, and β = 0.43 mmHg/year; 95% CI: 0.29, 0.56 for water arsenic and urinary creatinine-adjusted arsenic, respectively) in fully adjusted models. Likewise, individuals in the highest quartile of baseline arsenic exposure had a greater annual increase in diastolic blood pressure for water arsenic and urinary creatinine-adjusted arsenic, (β = 0.39 mmHg/year; 95% CI: 0.30, 0.49, and β = 0.45 mmHg/year; 95% CI: 0.36, 0.55, respectively) compared with those in the lowest quartile. Our findings suggest that long-term arsenic exposure may accelerate age-related increases in blood pressure. These findings may help explain associations between arsenic exposure and cardiovascular disease.

Chronic subhepatotoxic exposure to arsenic enhances hepatic injury caused by high fat diet in mice

International Nuclear Information System (INIS)

Tan, Min; Schmidt, Robin H.; Beier, Juliane I.; Watson, Walter H.; Zhong, Hai; States, J. Christopher; Arteel, Gavin E.

2011-01-01

Arsenic is a ubiquitous contaminant in drinking water. Whereas arsenic can be directly hepatotoxic, the concentrations/doses required are generally higher than present in the US water supply. However, physiological/biochemical changes that are alone pathologically inert can enhance the hepatotoxic response to a subsequent stimulus. Such a ‘2-hit’ paradigm is best exemplified in chronic fatty liver diseases. Here, the hypothesis that low arsenic exposure sensitizes liver to hepatotoxicity in a mouse model of non-alcoholic fatty liver disease was tested. Accordingly, male C57Bl/6J mice were exposed to low fat diet (LFD; 13% calories as fat) or high fat diet (HFD; 42% calories as fat) and tap water or arsenic (4.9 ppm as sodium arsenite) for ten weeks. Biochemical and histologic indices of liver damage were determined. High fat diet (± arsenic) significantly increased body weight gain in mice compared with low-fat controls. HFD significantly increased liver to body weight ratios; this variable was unaffected by arsenic exposure. HFD caused steatohepatitis, as indicated by histological assessment and by increases in plasma ALT and AST. Although arsenic exposure had no effect on indices of liver damage in LFD-fed animals, it significantly increased the liver damage caused by HFD. This effect of arsenic correlated with enhanced inflammation and fibrin extracellular matrix (ECM) deposition. These data indicate that subhepatotoxic arsenic exposure enhances the toxicity of HFD. These results also suggest that arsenic exposure might be a risk factor for the development of fatty liver disease in human populations. -- Highlights: ► Characterizes a mouse model of arsenic enhanced NAFLD. ► Arsenic synergistically enhances experimental fatty liver disease at concentrations that cause no overt hepatotoxicity alone. ► This effect is associated with increased inflammation.

EFFECTS OF DIBUTYL PHTHALATE IN MALE RABBITS FOLLOWING IN UTERO, ADOLESCENT OR POST-PUBERTAL EXPOSURE

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Effects of dibutyl phthalate in male rabbits following in utero, adolescent, or post-pubertal exposureTy T. Higuchi1, Jennifer S. Palmer1, L. Earl Gray Jr2., and D. N. Rao Veeramachaneni11Animal Reproduction and Biotechnology Laboratory, Colorado State University, Fort

EFFECTS OF ARSENIC EXPOSURE IN HUMAN HEALTH

Directory of Open Access Journals (Sweden)

Aline Sueli de Lima Rodrigues

2008-10-01

Full Text Available In recent years, ingestion of inorganic arsenic from drinking water has emerged as an important public health concern. It enters drinking water supplies from natural deposits in the earth or from agricultural and industrial practices, mainly the mining. The health consequences of chronic arsenic exposure include increased risk for various forms of cancer and numerous pathologic effects, such as cutaneous effects (hyperpigmentation and hyperkeratoses, gastrointestinal effects, vascular effects, diabetes mellitus, and peripheral neuropathy. This way, this study presents through a critical revision of the literature, the more relevant current aspects on the immunological consequences, carcinogenic and resulting genetics of the human intoxication for arsenic. They were identified and analyzed 50 works published on the subject among the years of 1979 and 2008, being used as main sources LILACS-BIREME MEDLINE/Index Medicus, SciELO and PubMed. The specific Arsênio e saúde humana effects of the intoxication for arsenic about the human health are not still completely elucidated. Thus, is possible that this element affects functions still unknown, becoming important the scientificexploration on the subject.

Investigating the effects of in utero benzene exposure on epigenetic modifications in maternal and fetal CD-1 mice

International Nuclear Information System (INIS)

Philbrook, Nicola A.; Winn, Louise M.

2015-01-01

Exposure to the ubiquitous environmental pollutant benzene is positively correlated with leukemia in adults and may be associated with childhood leukemia following in utero exposure. While numerous studies implicate oxidative stress and DNA damage as playing a role in benzene-mediated carcinogenicity, emerging evidence suggests that alterations in epigenetic regulations may be involved. The present study aimed to determine whether DNA methylation and/or various histone modifications were altered following in utero benzene exposure in CD-1 mice. Global DNA methylation and promoter-specific methylation of the tumor suppressor gene, p15, were assessed. Additionally, levels of acetylated histones H3, H4, and H3K56, as well as methylated histones H3K9 and H3K27 were assessed by Western blotting. A significant decrease in global DNA methylation of maternal bone marrow was observed following benzene exposure; however no effect on global DNA methylation was detected in fetal livers. Additionally, no effect of benzene exposure was observed on p15 promoter methylation or any measured histone modifications in both maternal bone marrow and fetal livers. These results suggest that the methodology used in the present study did not reveal alterations in DNA methylation and histone modifications following in utero exposure to benzene; however further experimentation investigating these modifications at the whole genome/epigenome level, as well as at later stages of benzene-induced carcinogenesis, are warranted. - Highlights: • Benzene exposure in pregnant mice decreased global DNA methylation in maternal bone marrow. • Benzene exposure in pregnant mice had no effect on global DNA methylation in fetal livers. • No effect of benzene exposure was observed on p15 promoter methylation. • No effect of benzene on measured histone modifications in both maternal bone marrow and fetal livers was observed.

Investigating the effects of in utero benzene exposure on epigenetic modifications in maternal and fetal CD-1 mice

Energy Technology Data Exchange (ETDEWEB)

Philbrook, Nicola A. [Department of Biomedical and Molecular Sciences, Graduate Program in Pharmacology and Toxicology, Queen' s University, Kingston, ON K7L3N6 (Canada); Winn, Louise M., E-mail: winnl@queensu.ca [Department of Biomedical and Molecular Sciences, Graduate Program in Pharmacology and Toxicology, Queen' s University, Kingston, ON K7L3N6 (Canada); School of Environmental Studies, Queen' s University, Kingston, ON K7L3N6 (Canada)

2015-11-15

Exposure to the ubiquitous environmental pollutant benzene is positively correlated with leukemia in adults and may be associated with childhood leukemia following in utero exposure. While numerous studies implicate oxidative stress and DNA damage as playing a role in benzene-mediated carcinogenicity, emerging evidence suggests that alterations in epigenetic regulations may be involved. The present study aimed to determine whether DNA methylation and/or various histone modifications were altered following in utero benzene exposure in CD-1 mice. Global DNA methylation and promoter-specific methylation of the tumor suppressor gene, p15, were assessed. Additionally, levels of acetylated histones H3, H4, and H3K56, as well as methylated histones H3K9 and H3K27 were assessed by Western blotting. A significant decrease in global DNA methylation of maternal bone marrow was observed following benzene exposure; however no effect on global DNA methylation was detected in fetal livers. Additionally, no effect of benzene exposure was observed on p15 promoter methylation or any measured histone modifications in both maternal bone marrow and fetal livers. These results suggest that the methodology used in the present study did not reveal alterations in DNA methylation and histone modifications following in utero exposure to benzene; however further experimentation investigating these modifications at the whole genome/epigenome level, as well as at later stages of benzene-induced carcinogenesis, are warranted. - Highlights: • Benzene exposure in pregnant mice decreased global DNA methylation in maternal bone marrow. • Benzene exposure in pregnant mice had no effect on global DNA methylation in fetal livers. • No effect of benzene exposure was observed on p15 promoter methylation. • No effect of benzene on measured histone modifications in both maternal bone marrow and fetal livers was observed.

Association between arsenic exposure from drinking water and hematuria: Results from the Health Effects of Arsenic Longitudinal Study

International Nuclear Information System (INIS)

McClintock, Tyler R.; Chen, Yu; Parvez, Faruque; Makarov, Danil V.; Ge, Wenzhen; Islam, Tariqul; Ahmed, Alauddin; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam; Slavkovich, Vesna; Bjurlin, Marc A.; Graziano, Joseph H.

2014-01-01

Arsenic (As) exposure has been associated with both urologic malignancy and renal dysfunction; however, its association with hematuria is unknown. We evaluated the association between drinking water As exposure and hematuria in 7843 men enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS). Cross-sectional analysis of baseline data was conducted with As exposure assessed in both well water and urinary As measurements, while hematuria was measured using urine dipstick. Prospective analyses with Cox proportional regression models were based on urinary As and dipstick measurements obtained biannually since baseline up to six years. At baseline, urinary As was significantly related to prevalence of hematuria (P-trend < 0.01), with increasing quintiles of exposure corresponding with respective prevalence odds ratios of 1.00 (reference), 1.29 (95% CI: 1.04–1.59), 1.41 (95% CI: 1.15–1.74), 1.46 (95% CI: 1.19–1.79), and 1.56 (95% CI: 1.27–1.91). Compared to those with relatively little absolute urinary As change during follow-up (− 10.40 to 41.17 μg/l), hazard ratios for hematuria were 0.99 (95% CI: 0.80–1.22) and 0.80 (95% CI: 0.65–0.99) for those whose urinary As decreased by > 47.49 μg/l and 10.87 to 47.49 μg/l since last visit, respectively, and 1.17 (95% CI: 0.94–1.45) and 1.36 (95% CI: 1.10–1.66) for those with between-visit increases of 10.40 to 41.17 μg/l and > 41.17 μg/l, respectively. These data indicate a positive association of As exposure with both prevalence and incidence of dipstick hematuria. This exposure effect appears modifiable by relatively short-term changes in drinking water As. - Highlights: • Hematuria is the most common symptom of urinary tract disease. • Arsenic exposure is associated with renal dysfunction and urologic malignancy. • Water arsenic was positively associated with prevalence and incidence of hematuria. • Reduction in exposure lowered hematuria risk especially in low-to-moderate exposed

Association between arsenic exposure from drinking water and hematuria: Results from the Health Effects of Arsenic Longitudinal Study

Energy Technology Data Exchange (ETDEWEB)

McClintock, Tyler R. [Department of Population Health, New York University School of Medicine, New York, NY (United States); Department of Environmental Medicine, New York University School of Medicine, New York, NY (United States); Department of Urology, New York University School of Medicine, New York, NY (United States); Chen, Yu, E-mail: yu.chen@nyumc.org [Department of Population Health, New York University School of Medicine, New York, NY (United States); Department of Environmental Medicine, New York University School of Medicine, New York, NY (United States); Parvez, Faruque [Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY (United States); Makarov, Danil V. [Department of Urology, New York University School of Medicine, New York, NY (United States); Robert F. Wagner Graduate School of Public Service, New York University, New York, NY (United States); United States Department of Veterans Affairs Harbor Healthcare System, New York, NY (United States); New York University Cancer Institute, New York, NY (United States); Ge, Wenzhen [Department of Population Health, New York University School of Medicine, New York, NY (United States); Department of Environmental Medicine, New York University School of Medicine, New York, NY (United States); Islam, Tariqul; Ahmed, Alauddin; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam [U-Chicago Research Bangladesh, Ltd., Dhaka (Bangladesh); Slavkovich, Vesna [Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY (United States); Bjurlin, Marc A. [Department of Urology, New York University School of Medicine, New York, NY (United States); Graziano, Joseph H. [Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY (United States); and others

2014-04-01

Arsenic (As) exposure has been associated with both urologic malignancy and renal dysfunction; however, its association with hematuria is unknown. We evaluated the association between drinking water As exposure and hematuria in 7843 men enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS). Cross-sectional analysis of baseline data was conducted with As exposure assessed in both well water and urinary As measurements, while hematuria was measured using urine dipstick. Prospective analyses with Cox proportional regression models were based on urinary As and dipstick measurements obtained biannually since baseline up to six years. At baseline, urinary As was significantly related to prevalence of hematuria (P-trend < 0.01), with increasing quintiles of exposure corresponding with respective prevalence odds ratios of 1.00 (reference), 1.29 (95% CI: 1.04–1.59), 1.41 (95% CI: 1.15–1.74), 1.46 (95% CI: 1.19–1.79), and 1.56 (95% CI: 1.27–1.91). Compared to those with relatively little absolute urinary As change during follow-up (− 10.40 to 41.17 μg/l), hazard ratios for hematuria were 0.99 (95% CI: 0.80–1.22) and 0.80 (95% CI: 0.65–0.99) for those whose urinary As decreased by > 47.49 μg/l and 10.87 to 47.49 μg/l since last visit, respectively, and 1.17 (95% CI: 0.94–1.45) and 1.36 (95% CI: 1.10–1.66) for those with between-visit increases of 10.40 to 41.17 μg/l and > 41.17 μg/l, respectively. These data indicate a positive association of As exposure with both prevalence and incidence of dipstick hematuria. This exposure effect appears modifiable by relatively short-term changes in drinking water As. - Highlights: • Hematuria is the most common symptom of urinary tract disease. • Arsenic exposure is associated with renal dysfunction and urologic malignancy. • Water arsenic was positively associated with prevalence and incidence of hematuria. • Reduction in exposure lowered hematuria risk especially in low-to-moderate exposed

Long-term exposure to arsenic affects head kidney and impairs humoral immune responses of Clarias batrachus

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Ghosh, Debabrata [Immunobiology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India); Datta, Soma [Immunobiology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India); Bhattacharya, Shelley [Environmental Toxicology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India); Mazumder, Shibnath [Immunobiology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India)]. E-mail: shibnath1@yahoo.co.in

2007-02-15

The present study was aimed at determining the effects of long-term arsenic exposure on the head kidney (HK) and ensuing humoral immune responses in Clarias batrachus L. Long-term exposure (150 days) to non-lethal concentrations of arsenic (42.42 {mu}M) resulted in significant time-dependent alterations in HK cell number eventually affecting the HK somatic index. Prolonged exposure to arsenic also suppressed HK-B cell proliferation and led to significant reduction in serum immunoglobulin levels and antigen-specific serum bacterial agglutinin titers. A decline in the number of antigen-specific plaque-forming cells with duration of arsenic exposure was noted in the HK. Enzyme linked immunosorbent assays further revealed that arsenic exposure inhibited the release of 'IL-4 like factors' from HK-T cells. Histological studies documented time-dependent changes in the structure and cellular composition of HK characterized by extensive lymphocytopenia, decrease in melano-macrophage population and hemosiderin accumulation. From exposure-challenge studies with Aeromonas hydrophila it was evident that pathogens could efficiently disseminate and colonize distant host tissues in the exposed fish. Moreover, the ability to decrease the pathogen load was also significantly reduced in the arsenic-exposed fish. Thus long-term exposure to non-lethal concentrations of arsenic affects HK and interferes with the humoral immune system of C. batrachus rendering them immunocompromised and susceptible to pathogenic challenge.

Long-term exposure to arsenic affects head kidney and impairs humoral immune responses of Clarias batrachus

International Nuclear Information System (INIS)

Ghosh, Debabrata; Datta, Soma; Bhattacharya, Shelley; Mazumder, Shibnath

2007-01-01

The present study was aimed at determining the effects of long-term arsenic exposure on the head kidney (HK) and ensuing humoral immune responses in Clarias batrachus L. Long-term exposure (150 days) to non-lethal concentrations of arsenic (42.42 μM) resulted in significant time-dependent alterations in HK cell number eventually affecting the HK somatic index. Prolonged exposure to arsenic also suppressed HK-B cell proliferation and led to significant reduction in serum immunoglobulin levels and antigen-specific serum bacterial agglutinin titers. A decline in the number of antigen-specific plaque-forming cells with duration of arsenic exposure was noted in the HK. Enzyme linked immunosorbent assays further revealed that arsenic exposure inhibited the release of 'IL-4 like factors' from HK-T cells. Histological studies documented time-dependent changes in the structure and cellular composition of HK characterized by extensive lymphocytopenia, decrease in melano-macrophage population and hemosiderin accumulation. From exposure-challenge studies with Aeromonas hydrophila it was evident that pathogens could efficiently disseminate and colonize distant host tissues in the exposed fish. Moreover, the ability to decrease the pathogen load was also significantly reduced in the arsenic-exposed fish. Thus long-term exposure to non-lethal concentrations of arsenic affects HK and interferes with the humoral immune system of C. batrachus rendering them immunocompromised and susceptible to pathogenic challenge

Induction of glutathione synthesis in human hepatocytes by acute and chronic arsenic exposure: Differential roles of mitogen-activated protein kinases

International Nuclear Information System (INIS)

Hou, Yongyong; Wang, Yi; Wang, Huihui; Xu, Yuanyuan

2014-01-01

Highlights: • Arsenic exposure increased intracellular levels of glutathione. • Mitogen-activated protein kinases were involved in glutathione homeostasis. • ERK contributed to glutathione synthesis during acute arsenic exposure. • Glutathione synthesis was regulated by p38 at least in part independent of NRF2 during chronic arsenic exposure. - Abstract: Glutathione (GSH) is a vital component of antioxidant defense which protects cells from toxic insults. Previously we found intracellular GSH was involved in cell resistance against arsenic-induced cytotoxicity. However, molecular mechanisms of GSH homeostasis during arsenic exposure are largely undefined. Here, we investigated roles of mitogen-activated protein kinases (MAPKs) in GSH synthesis pathway with two arsenic exposure strategies by using Chang human hepatocytes. In one strategy, acute arsenic exposure (20 μM, 24 h) was applied, as MAPK signaling is generally considered to be transient. In the other one, chronic arsenic exposure (500 nM, 20 weeks) was applied, which mimicked the general human exposure to arsenic. We found that acute arsenic exposure activated extracellular signal-regulated 1/2 kinases (ERK1/2) and c-Jun N-terminal kinase (JNK) in parallel with increased transcription and nuclear translocation of factor-erythroid 2-related factor 2 (NRF2) and enhanced expression of γ-glutamyl cysteine ligase catalytic subunit (GCLC), resulting in elevated intracellular GSH levels. Specific ERK inhibitor abolished arsenic-induced NRF2 nuclear translocation and GSH synthesis. During chronic arsenic exposure which induced a malignant cellular phenotype, continuous p38 activation and NRF2 nuclear translocation were observed with enhanced GSH synthesis. Specific p38 inhibitor attenuated arsenic-enhanced GSH synthesis without changing NRF2 nuclear translocation. Taken together, our results indicate MAPK pathways play an important role in cellular GSH homeostasis in response to arsenic. However, the

A Case control study of cardiovascular disease and arsenic exposure in Inner Mongolia, China

Science.gov (United States)

Background: Millions of people are at risk from the adverse effects of waterborne arsenic. Although the cardiovascular effects of high exposures to arsenic have been well documented, few individual level prospective studies have assessed cardiovascular risk at moderate exposures....

A Systematic Review of Arsenic Exposure and Its Social and Mental Health Effects with Special Reference to Bangladesh

Directory of Open Access Journals (Sweden)

Alexander Kraemer

2009-05-01

Full Text Available Undergroundwater in many regions of the world is contaminated with high concentrations of arsenic and the resulting toxicity has created a major environmental and public health problem in the affected regions. Chronic arsenic exposure can cause many diseases, including various physical and psychological harms. Although the physical problems caused by arsenic toxicity are well reported in literature, unfortunately the consequences of arsenic exposure on mental health are not adequately studied. Therefore we conducted a review of the available literature focusing on the social consequences and detrimental effects of arsenic toxicity on mental health. Chronic arsenic exposures have serious implications for its victims (i.e. arsenicosis patients and their families including social instability, social discrimination, refusal of victims by community and families, and marriage-related problems. Some studies conducted in arsenic affected areas revealed that arsenic exposures are associated with various neurologic problems. Chronic arsenic exposure can lead to mental retardation and developmental disabilities such as physical, cognitive, psychological, sensory and speech impairments. As health is defined by the World Health Organization as “a state of complete physical, mental and social wellbeing”, the social dimensions have a large impact on individual’s mental health. Furthermore studies in China und Bangladesh have shown that mental health problems (e.g. depression are more common among the people affected by arsenic contamination. Our study indicates various neurological, mental and social consequences among arsenic affected victims. Further studies are recommended in arsenic-affected areas to understand the underlying mechanisms of poor mental health caused by arsenic exposure.

Association between type 2 diabetes and chronic arsenic exposure in drinking water: a cross sectional study in Bangladesh.

Science.gov (United States)

Islam, Rafiqul; Khan, Ismail; Hassan, Sheikh Nazmul; McEvoy, Mark; D'Este, Catherine; Attia, John; Peel, Roseanne; Sultana, Munira; Akter, Shahnaz; Milton, Abul Hasnat

2012-06-07

Chronic exposure to high level of inorganic arsenic in drinking water has been associated with Type 2 Diabetes (T2D). Most research has been ecological in nature and has focused on high levels of arsenic exposure with few studies directly measuring arsenic levels in drinking water as an index of arsenic exposure. The effect of low to moderate levels of arsenic exposure on diabetes risk is largely unknown thus our study is adding further knowledge over previous works. This cross sectional study was conducted in 1004 consenting women and men from 1682 eligible participants yielding a participation rate of 60%. These participants are aged >30 years and were living in Bangladesh and had continuously consumed arsenic-contaminated drinking water for at least 6 months. T2D cases were diagnosed using glucometer following the new diagnostic criteria (Fasting Blood Glucose > 126 mg/dl) from the WHO guideline (WHO 2006), or a self-reported physician diagnosis of type 2 diabetes. Association between T2D and chronic arsenic exposure was estimated by multiple logistic regression with adjustment for age, sex, education, Body Mass Index (BMI) and family history of T2D. A total of 1004 individuals participated in the study. The prevalence of T2D was 9% (95% CI 7-11%). After adjustment for diabetes risk factors, an increased risk of type 2 diabetes was observed for arsenic exposure over 50 μg/L with those in the highest category having almost double the risk of type 2 diabetes (OR=1.9 ; 95% CI 1.1-3.5). For most levels of arsenic exposure, the risk estimates are higher with longer exposure; a dose-response pattern was also observed. These findings suggest an association between chronic arsenic exposure through drinking water and T2D. Risks are generally higher with longer duration of arsenic exposure. The risk of T2D is highest among those who were exposed to the highest concentration of arsenic for more than 10 years.

Phthalate and bisphenol A exposure during in utero windows of susceptibility in relation to reproductive hormones and pubertal development in girls.

Science.gov (United States)

Watkins, Deborah J; Sánchez, Brisa N; Téllez-Rojo, Martha Maria; Lee, Joyce M; Mercado-García, Adriana; Blank-Goldenberg, Clara; Peterson, Karen E; Meeker, John D

2017-11-01

Over the past several decades, the age of pubertal onset in girls has shifted downward worldwide. As early pubertal onset is associated with increased risky behavior and psychological issues during adolescence and cardiometabolic disease and cancer in adulthood, this is an important public health concern. Exposure to endocrine disrupting chemicals during critical windows of in utero development may play a role in this trend. Our objective was to investigate trimester-specific phthalate and BPA exposure in relation to pubertal development among girls in the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort. We measured maternal urinary phthalate metabolites and BPA in samples collected during the first, second, and third trimesters of pregnancy. To assess reproductive development among their female children, we measured serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG), and assessed sexual maturation, including Tanner staging for breast and pubic hair development and menarche status, at age 8-13 years (n = 120). We used linear and logistic regression to examine measures of trimester-specific in utero exposure as predictors of peripubertal hormone levels and pubertal onset, respectively. In secondary analyses, we evaluated estimated exposure at the midpoint of the first trimester and rates of change in exposure across pregnancy in relation to outcomes. Several phthalate metabolites measured throughout in utero development were associated with higher serum testosterone concentrations, while a number of metabolites measured in the third trimester were associated with higher DHEA-S. For example, an interquartile range (IQR) increase in mean monoethyl phthalate (MEP) levels across pregnancy was associated with 44% higher peripubertal testosterone (95% CI: 13-83%), while an IQR increase in di-2-ethylhexyl phthalate metabolites (ΣDEHP) specifically in the third trimester

Exercise Prevents Memory Impairment Induced by Arsenic Exposure in Mice: Implication of Hippocampal BDNF and CREB

OpenAIRE

Sun, Bao-Fei; Wang, Qing-Qing; Yu, Zi-Jiang; Yu, Yan; Xiao, Chao-Lun; Kang, Chao-Sheng; Ge, Guo; Linghu, Yan; Zhu, Jun-De; Li, Yu-Mei; Li, Qiang-Ming; Luo, Shi-Peng; Yang, Dang; Li, Lin; Zhang, Wen-Yan

2015-01-01

High concentrations of arsenic, which can be occasionally found in drinking water, have been recognized as a global health problem. Exposure to arsenic can disrupt spatial memory; however, the underlying mechanism remains unclear. In the present study, we tested whether exercise could interfere with the effect of arsenic exposure on the long-term memory (LTM) of object recognition in mice. Arsenic (0, 1, 3, and 10 mg/ kg, i.g.) was administered daily for 12 weeks. We found that arsenic at dos...

Neonatal outcomes following exposure in utero to fallout from Chernobyl.

Science.gov (United States)

Hatch, Maureen; Little, Mark P; Brenner, Alina V; Cahoon, Elizabeth K; Tereshchenko, Valery; Chaikovska, Ludmyla; Pasteur, Igor; Likhtarov, Ilya; Bouville, Andre; Shpak, Victor; Bolshova, Olena; Zamotayeva, Galyna; Grantz, Katherine; Sun, Liping; Mabuchi, Kiyohiko; Albert, Paul; Tronko, Mykola

2017-12-01

Iodine 131 (I-131), the principal component of nuclear fallout from the Chernobyl accident, concentrates in the thyroid gland and may pose risks to fetal development. To evaluate this, neonatal outcomes following the accident in April of 1986 were investigated in a cohort of 2582 in utero-exposed individuals from northern Ukraine for whom estimates of fetal thyroid I-131 dose were available. We carried out a retrospective review of cohort members' prenatal, delivery and newborn records. The relationships of dose with neonatal anthropometrics and gestational length were modeled via linear regression with adjustment for potentially confounding variables. We found similar, statistically significant dose-dependent reductions in both head circumference (-1.0 cm/Gy, P = 0.005) and chest circumference (-0.9 cm/Gy, P = 0.023), as well as a similar but non-significant reduction in neonatal length (-0.6 cm/Gy, P = 0.169). Gestational length was significantly increased with increasing fetal dose (0.5 wks/Gy, P = 0.007). There was no significant (P > 0.1) effect of fetal dose on birth weight. The observed associations of radioiodine exposure with decreased head and chest circumference are consistent with those observed in the Japanese in utero-exposed atomic bomb survivors.

Behavioural and physical effects of arsenic exposure in fish are aggravated by aquatic algae.

Science.gov (United States)

Magellan, Kit; Barral-Fraga, Laura; Rovira, Marona; Srean, Pao; Urrea, Gemma; García-Berthou, Emili; Guasch, Helena

2014-11-01

Arsenic contamination has global impacts and freshwaters are major arsenic repositories. Arsenic toxicity depends on numerous interacting factors which makes effects difficult to estimate. The use of aquatic algae is often advocated for bioremediation of arsenic contaminated waters as they absorb arsenate and transform it into arsenite and methylated chemical species. Fish are another key constituent of aquatic ecosystems. Contamination in natural systems is often too low to cause mortality but sufficient to interfere with normal functioning. Alteration of complex, naturally occurring fish behaviours such as foraging and aggression are ecologically relevant indicators of toxicity and ideal for assessing sublethal impacts. We examined the effects of arsenic exposure in the invasive mosquitofish, Gambusia holbrooki, in a laboratory experiment incorporating some of the complexity of natural systems by including the interacting effects of aquatic algae. Our aims were to quantify the effects of arsenic on some complex behaviours and physical parameters in mosquitofish, and to assess whether the detoxifying mechanisms of algae would ameliorate any effects of arsenic exposure. Aggression increased significantly with arsenic whereas operculum movement decreased non-significantly and neither food capture efficiency nor consumption were notably affected. Bioaccumulation increased with arsenic and unexpectedly so did fish biomass. Possibly increased aggression facilitated food resource defence allowing fish to gain weight. The presence of algae aggravated the effects of arsenic exposure. For increase in fish biomass, algae acted antagonistically with arsenic, resulting in a disadvantageous reduction in weight gained. For bioaccumulation the effects were even more severe, as algae operated additively with arsenic to increase arsenic uptake and/or assimilation. Aggression was also highest in the presence of both algae and arsenic. Bioremediation of arsenic contaminated waters

Site-specific data confirm arsenic exposure predicted by the U.S. Environmental Protection Agency.

OpenAIRE

Walker, S; Griffin, S

1998-01-01

The EPA uses an exposure assessment model to estimate daily intake to chemicals of potential concern. At the Anaconda Superfund site in Montana, the EPA exposure assessment model was used to predict total and speciated urinary arsenic concentrations. Predicted concentrations were then compared to concentrations measured in children living near the site. When site-specific information on concentrations of arsenic in soil, interior dust, and diet, site-specific ingestion rates, and arsenic abso...

Total and inorganic arsenic in dietary supplements based on herbs, other botanicals and algae—a possible contributor to inorganic arsenic exposure

DEFF Research Database (Denmark)

Hedegaard, Rikke Susanne Vingborg; Rokkjær, Inge; Sloth, Jens Jørgen

2013-01-01

The content of total and inorganic arsenic was determined in 16 dietary supplements based on herbs, other botanicals and algae purchased on the Danish market. The dietary supplements originated from various regions, including Asia, Europe and USA. The contents of total and inorganic arsenic...... was determined by inductively coupled plasma mass spectrometry (ICP-MS) and anion exchange HPLC-ICP-MS, respectively, were in the range of 0.58 to 5.0 mgkg−1 and 0.03 to 3.2 mg kg−1, respectively, with a ratio between inorganic arsenic and total arsenic ranging between 5 and 100 %. Consumption of the recommended...... dose of the individual dietary supplement would lead to an exposure to inorganic arsenic within the range of 0.07 to 13 μg day−1. Such exposure from dietary supplements would in worst case constitute 62.4 % of the range of benchmark dose lower confidence limit values (BMDL01 at 0.3 to 8 μg kg bw−1 kg−1...

Oxidative DNA damage of peripheral blood polymorphonuclear leukocytes, selectively induced by chronic arsenic exposure, is associated with extent of arsenic-related skin lesions

International Nuclear Information System (INIS)

Pei, Qiuling; Ma, Ning; Zhang, Jing; Xu, Wenchao; Li, Yong; Ma, Zhifeng; Li, Yunyun; Tian, Fengjie; Zhang, Wenping; Mu, Jinjun; Li, Yuanfei; Wang, Dongxing; Liu, Haifang; Yang, Mimi; Ma, Caifeng; Yun, Fen

2013-01-01

There is increasing evidence that oxidative stress is an important risk factor for arsenic-related diseases. Peripheral blood leukocytes constitute an important defense against microorganisms or pathogens, while the research on the impact of chronic arsenic exposure on peripheral blood leukocytes is much more limited, especially at low level arsenic exposure. The purpose of the present study was to explore whether chronic arsenic exposure affects oxidative stress of peripheral blood leukocytes and possible linkages between oxidative stress and arsenic-induced skin lesions. 75 male inhabitants recruited from an As-endemic region of China were investigated in the present study. The classification of arsenicosis was based on the degree of skin lesions. Arsenic levels were measured in drinking water and urine by Atomic Fluorescence Spectroscopy. Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) was tested by Enzyme-Linked Immunosorbent Assay. 8-OHdG of peripheral blood leukocytes was evaluated using immunocytochemical staining. 8-OHdG-positive reactions were only present in polymorphonuclear leukocytes (PMNs), but not in monocytes (MNs). The 8-OHdG staining of PMN cytoplasm was observed in all investigated populations, while the 8-OHdG staining of PMN nuclei was frequently found along with the elevated amounts of cell debris in individuals with skin lesion. Urinary arsenic levels were increased in the severe skin lesion group compared with the normal group. No relationship was observed between drinking water arsenic or urine 8-OHdG and the degree of skin lesions. These findings indicated that the target and persistent oxidative stress in peripheral blood PMNs may be employed as a sensitive biomarker directly to assess adverse health effects caused by chronic exposure to lower levels of arsenic. -- Highlights: ► Male inhabitants were investigated from an As-endemic region of China. ► 8-OHdG-positive reactions were only present in polymorphonuclear leukocytes (PMNs). �

Blood arsenic as a biomarker of arsenic exposure: Results from a prospective study

International Nuclear Information System (INIS)

Hall, Marni; Chen Yu; Ahsan, Habibul; Slavkovich, Vesna; Geen, Alexander van; Parvez, Faruque; Graziano, Joseph

2006-01-01

Exposure to arsenic (As)-contaminated drinking water affects millions of people worldwide. Arsenic exposure is associated with skin lesions, skin, lung, kidney and liver cancers, neurologic and cardiovascular effects. Past studies involving biomarkers of As exposure have typically examined urinary As (UAs) (adjusted for urinary creatinine), hair or toenail As, but not blood As (BAs) since blood concentrations are exceedingly low and are not detectable by conventional atomic absorption spectrophotometric techniques. In a case-cohort analysis of 303 newly diagnosed cases of skin lesions, and 849 subcohort members randomly selected from 8092 participants in the health effects of as longitudinal study (HEALS) in Araihazar, Bangladesh, we measured blood, urine and water As concentrations, and examined their associations with each other, and with the risk for skin lesions. BAs concentrations were highly correlated with creatinine-adjusted UAs concentrations (r = 0.85) and with water As (WAs) (r = 0.75). We observed consistent dose-response relationships between the risk of skin lesions and all the measures of As exposure. Rate ratios (RRs) for skin lesions by quintile of As exposure, adjusted for age and gender, revealed that the two highest quintiles were significantly related to an increased risk of skin lesions for each measure of exposure: BAs, UAs, WAs and a time-weighted water As variable. This prospective study confirms the increased risk of skin lesions in relation to As concentrations in blood, urine and water and also establishes that BAs is a useful biomarker of As exposure in this study population

A Prospective Study of Arsenic Exposure From Drinking Water and Incidence of Skin Lesions in Bangladesh

Science.gov (United States)

Argos, Maria; Kalra, Tara; Pierce, Brandon L.; Chen, Yu; Parvez, Faruque; Islam, Tariqul; Ahmed, Alauddin; Hasan, Rabiul; Hasan, Khaled; Sarwar, Golam; Levy, Diane; Slavkovich, Vesna; Graziano, Joseph H.; Rathouz, Paul J.; Ahsan, Habibul

2011-01-01

Elevated concentrations of arsenic in groundwater pose a public health threat to millions of people worldwide. The authors aimed to evaluate the association between arsenic exposure and skin lesion incidence among participants in the Health Effects of Arsenic Longitudinal Study (HEALS). The analyses used data on 10,182 adults free of skin lesions at baseline through the third biennial follow-up of the cohort (2000–2009). Discrete-time hazard regression models were used to estimate hazard ratios and 95% confidence intervals for incident skin lesions. Multivariate-adjusted hazard ratios for incident skin lesions comparing 10.1–50.0, 50.1–100.0, 100.1–200.0, and ≥200.1 μg/L with ≤10.0 μg/L of well water arsenic exposure were 1.17 (95% confidence interval (CI): 0.92, 1.49), 1.69 (95% CI: 1.33, 2.14), 1.97 (95% CI: 1.58, 2.46), and 2.98 (95% CI: 2.40, 3.71), respectively (Ptrend = 0.0001). Results were similar for the other measures of arsenic exposure, and the increased risks remained unchanged with changes in exposure in recent years. Dose-dependent associations were more pronounced in females, but the incidence of skin lesions was greater in males and older individuals. Chronic arsenic exposure from drinking water was associated with increased incidence of skin lesions, even at low levels of arsenic exposure (<100 μg/L). PMID:21576319

In utero exposure to toxic air pollutants and risk of childhood autism.

Science.gov (United States)

von Ehrenstein, Ondine S; Aralis, Hilary; Cockburn, Myles; Ritz, Beate

2014-11-01

Genetic and environmental factors are believed to contribute to the development of autism, but relatively few studies have considered potential environmental risks. Here, we examine risks for autism in children related to in utero exposure to monitored ambient air toxics from urban emissions. Among the cohort of children born in Los Angeles County, California, 1995-2006, those whose mothers resided during pregnancy in a 5-km buffer around air toxics monitoring stations were included (n = 148,722). To identify autism cases in this cohort, birth records were linked to records of children diagnosed with primary autistic disorder at the California Department of Developmental Services between 1998 and 2009 (n = 768). We calculated monthly average exposures during pregnancy for 24 air toxics selected based on suspected or known neurotoxicity or neurodevelopmental toxicity. Factor analysis helped us identify the correlational structure among air toxics, and we estimated odds ratios (ORs) for autism from logistic regression analyses. Autism risks were increased per interquartile range increase in average concentrations during pregnancy of several correlated toxics mostly loading on 1 factor, including 1,3-butadiene (OR = 1.59 [95% confidence interval = 1.18-2.15]), meta/para-xylene (1.51 [1.26-1.82]), other aromatic solvents, lead (1.49 [1.23-1.81]), perchloroethylene (1.40 [1.09-1.80]), and formaldehyde (1.34 [1.17-1.52]), adjusting for maternal age, race/ethnicity, nativity, education, insurance type, parity, child sex, and birth year. Risks for autism in children may increase following in utero exposure to ambient air toxics from urban traffic and industry emissions, as measured by community-based air-monitoring stations.

Effects of in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on sexual differentiation in rats

Energy Technology Data Exchange (ETDEWEB)

Ikeda, M.; Suzuki, C.; Yamashita, J.; Tomita, T. [Univ. of Shizuoka, Shizuoka (Japan); Tohyama, C. [National Inst. for Environmental Studies, Tsukuba (Japan)

2004-09-15

We have previously reported that in utero and lactational exposure of 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD, 200 ng/kg) to malignant Holtzman rats induced demasculinization of sexually-dimorphic behavior and inhibited the development of the sexually dimorphic nucleus of the preoptic area (SDN-POA) in male offspring. However, these effects of TCDD were not observed in higher dose (800 ng/kg) of TCDD-exposed male offspring. The shortening of anogenitgal distance and the decrease of the ventral prostate weight in male offspring by in utero and lactational TCDD exposure were reported and these effects of TCDD were observed in a dose-dependent manner. This study was undertaken to examine the influence of the TCDD exposure at the varying dosage levels on sexually dimorphic behavior and the development of SDN-POA.

Low-level arsenic exposure via drinking water consumption and female fecundity - A preliminary investigation

Energy Technology Data Exchange (ETDEWEB)

Susko, Michele L. [Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, New York (United States); Bloom, Michael S., E-mail: mbloom@albany.edu [Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, New York (United States); Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, New York (United States); Neamtiu, Iulia A. [Health Department, Environmental Health Center, Cluj-Napoca (Romania); IMOGEN Research Institute, Cluj-Napoca (Romania); Appleton, Allison A. [Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, New York (United States); Surdu, Simona [Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, New York (United States); Pop, Cristian [Physico-chemical and Biotoxicological Analysis Laboratory, Environmental Health Center, Cluj-Napoca (Romania); Cluj School of Public Health - College of Political, Administrative and Communication Sciences, Babeș-Bolyai University, Cluj-Napoca (Romania); Faculty of Environmental Science and Engineering, Babeș-Bolyai University, Cluj-Napoca (Romania); Fitzgerald, Edward F. [Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, New York (United States); Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, New York (United States); Anastasiu, Doru [University of Medicine and Pharmacy “Victor Babeș”, Timișoara (Romania); Obstetrics and Gynecology Department of the Emergency County Hospital, Timișoara (Romania); and others

2017-04-15

High level arsenic exposure is associated with reproductive toxicity in experimental and observational studies; however, few data exist to assess risks at low levels. Even less data are available to evaluate the impact of low level arsenic exposure on human fecundity. Our aim in this pilot study was a preliminary evaluation of associations between low level drinking water arsenic contamination and female fecundity. This retrospective study was conducted among women previously recruited to a hospital-based case-control study of spontaneous pregnancy loss in Timiá¹£ County, Romania. Women (n=94) with planned pregnancies of 5–20 weeks gestation completed a comprehensive physician-administered study questionnaire and reported the number of menstrual cycles attempting to conceive as the time to pregnancy (TTP). Drinking water samples were collected from residential drinking water sources and we determined arsenic levels using hydride generation-atomic absorption spectrometry (HG-AAS). Multivariable Cox-proportional hazards regression with Efron approximation was employed to evaluate TTP as a function of drinking water arsenic concentrations among planned pregnancies, adjusted for covariates. There was no main effect for drinking water arsenic exposure, yet the conditional probability for pregnancy was modestly lower among arsenic exposed women with longer TTPs, relative to women with shorter TTPs, and relative to unexposed women. For example, 1 µg/L average drinking water arsenic conferred 5%, 8%, and 10% lower likelihoods for pregnancy in the 6th, 9th, and 12th cycles, respectively (P=0.01). While preliminary, our results suggest that low level arsenic contamination in residential drinking water sources may further impair fecundity among women with longer waiting times; however, this hypothesis requires confirmation by a future, more definitive study. - Highlights: • We assessed low level drinking water arsenic as a predictor of fecundability. • Arsenic did

Low-level arsenic exposure via drinking water consumption and female fecundity - A preliminary investigation

International Nuclear Information System (INIS)

Susko, Michele L.; Bloom, Michael S.; Neamtiu, Iulia A.; Appleton, Allison A.; Surdu, Simona; Pop, Cristian; Fitzgerald, Edward F.; Anastasiu, Doru

2017-01-01

High level arsenic exposure is associated with reproductive toxicity in experimental and observational studies; however, few data exist to assess risks at low levels. Even less data are available to evaluate the impact of low level arsenic exposure on human fecundity. Our aim in this pilot study was a preliminary evaluation of associations between low level drinking water arsenic contamination and female fecundity. This retrospective study was conducted among women previously recruited to a hospital-based case-control study of spontaneous pregnancy loss in Timiá¹£ County, Romania. Women (n=94) with planned pregnancies of 5–20 weeks gestation completed a comprehensive physician-administered study questionnaire and reported the number of menstrual cycles attempting to conceive as the time to pregnancy (TTP). Drinking water samples were collected from residential drinking water sources and we determined arsenic levels using hydride generation-atomic absorption spectrometry (HG-AAS). Multivariable Cox-proportional hazards regression with Efron approximation was employed to evaluate TTP as a function of drinking water arsenic concentrations among planned pregnancies, adjusted for covariates. There was no main effect for drinking water arsenic exposure, yet the conditional probability for pregnancy was modestly lower among arsenic exposed women with longer TTPs, relative to women with shorter TTPs, and relative to unexposed women. For example, 1 µg/L average drinking water arsenic conferred 5%, 8%, and 10% lower likelihoods for pregnancy in the 6th, 9th, and 12th cycles, respectively (P=0.01). While preliminary, our results suggest that low level arsenic contamination in residential drinking water sources may further impair fecundity among women with longer waiting times; however, this hypothesis requires confirmation by a future, more definitive study. - Highlights: • We assessed low level drinking water arsenic as a predictor of fecundability. • Arsenic did

In-utero exposure to DDT and cognitive development among infants and school-aged children

Science.gov (United States)

Jusko, Todd A.; Klebanoff, Mark A.; Brock, John W.; Longnecker, Matthew P.

2012-01-01

Background Dichlorodiphenyltrichloroethane (DDT) continues to be used for control of infectious diseases in several countries. In-utero exposure to DDT and dichlorodiphenyldichloroethylene (DDE) has been associated with developmental and cognitive impairment among children. We examined this association in an historical cohort in which the level of exposure was greater than in previous studies. Methods The association of in-utero DDT and DDE exposure with infant and child neurodevelopment was examined in approximately 1100 subjects in the Collaborative Perinatal Project, a prospective birth cohort enrolling pregnant women from 12 study centers in the U.S. from 1959 to 1965. Maternal DDT and DDE concentrations were measured in archived serum specimens. Infant mental and motor development was assessed at age 8 months using the Bayley Scales of Infant Development, and child cognitive development was assessed at age 7 years using the Wechsler Intelligence Scale for Children. Results Although levels of both DDT and DDE were relatively high in this population (median DDT concentration, 8.9 µg/L; DDE, 24.5 µg/L), neither was related to Mental or Psychomotor Development scores on the Bayley Scales or to Full-Scale IQ at 7 years of age. Categorical analyses showed no evidence of dose-response for either maternal DDT or DDE, and estimates of the association between continuous measures of exposure and neurodevelopment were indistinguishable from 0. Conclusions Adverse associations were not observed between maternal serum DDT and DDE concentrations and offspring neurodevelopment at 8 months or 7 years of age in this cohort. PMID:22766752

Mullerian agenesis associated with in-utero thalidomide exposure: A case report

Directory of Open Access Journals (Sweden)

Sarah Dotters-Katz

2013-09-01

Full Text Available Thalidomide is a well-known teratogen, which is experiencing resurgence as new uses are identified. Exposure is classically associated with limb deformities, such as: dysmelia, phocomelia, preaxial hypoplasia and polydactyly, in addition to visceral anomalies that have been documented as well. We report a case of a 38 year-old nulligravid female, who was previously evaluated for primary amenorrhea, and given the presumptive false diagnosis of an imperforate hymen. On magnetic resonance imaging (MRI exam, she was noted to have uterovaginal agenesis. The implications of thalidomide on women’s health extend beyond external birth defects. Although, most commonly associated with limb deformities, there may also be gynecologic implications of in utero exposure. As this medication is increasingly used for various medical conditions, obstetricians/gynecologists need to remain aware of this potential mullerian teratogenic effect.

Long-term exposure to low-level arsenic in drinking water and diabetes incidence

DEFF Research Database (Denmark)

Bräuner, Elvira Vaclavik; Nordsborg, Rikke Baastrup; Andersen, Zorana Jovanovic

2014-01-01

BACKGROUND: Established causes of diabetes do not fully explain the present epidemic. High-level arsenic exposure has been implicated in diabetes risk, but the effect of low-level arsenic exposure in drinking water remains unclear. OBJECTIVE: We sought to determine whether long-term exposure to low......-level arsenic in drinking water in Denmark is associated with an increased risk of diabetes using a large prospective cohort. METHODS: During 1993-1997, we recruited 57,053 persons. We followed each cohort member for diabetes occurrence from enrollment until 31 December 2006. We traced and geocoded residential...... exposure and diabetes incidence, separately for two definitions of diabetes: all cases and a more strict definition in which cases of diabetes based solely on blood glucose results were excluded. RESULTS: Over a mean follow-up period of 9.7 years for 52,931 eligible participants, there were a total of 4...

Biological and environmental hazards associated with exposure to chemical warfare agents: arsenicals.

Science.gov (United States)

Li, Changzhao; Srivastava, Ritesh K; Athar, Mohammad

2016-08-01

Arsenicals are highly reactive inorganic and organic derivatives of arsenic. These chemicals are very toxic and produce both acute and chronic tissue damage. On the basis of these observations, and considering the low cost and simple methods of their bulk syntheses, these agents were thought to be appropriate for chemical warfare. Among these, the best-known agent that was synthesized and weaponized during World War I (WWI) is Lewisite. Exposure to Lewisite causes painful inflammatory and blistering responses in the skin, lung, and eye. These chemicals also manifest systemic tissue injury following their cutaneous exposure. Although largely discontinued after WWI, stockpiles are still known to exist in the former Soviet Union, Germany, Italy, the United States, and Asia. Thus, access by terrorists or accidental exposure could be highly dangerous for humans and the environment. This review summarizes studies that describe the biological, pathophysiological, toxicological, and environmental effects of exposure to arsenicals, with a major focus on cutaneous injury. Studies related to the development of novel molecular pathobiology-based antidotes against these agents are also described. © 2016 New York Academy of Sciences.

Biological and environmental hazards associated with exposure to chemical warfare agents: arsenicals

Science.gov (United States)

Li, Changzhao; Srivastava, Ritesh K.; Athar, Mohammad

2016-01-01

Arsenicals are highly reactive inorganic and organic derivatives of arsenic. These chemicals are very toxic and produce both acute and chronic tissue damage. Based on these observations, and considering the low cost and simple methods of their bulk syntheses, these agents were thought to be appropriate for chemical warfare. Among these, the most known agent synthesized and weaponized during World War I (WWI) is Lewisite. Exposure to Lewisite causes painful inflammatory and blistering responses in the skin, lung, and eye. These chemicals also manifest systemic tissue injury following their cutaneous exposure. Although largely discontinued after WWI, their stockpiles are still known to exist in the former Soviet Union, Germany, Italy, the United States, and Asia. Thus, their access by terrorists or accidental exposure could be highly dangerous for humans and the environment. This review summarizes studies which describe the biological, pathophysiological, toxicological, and environmental effects of exposure to arsenicals, with a major focus on cutaneous injury. Studies related to the development of novel molecular pathobiology–based antidotes against these agents are also described. PMID:27636894

Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1

International Nuclear Information System (INIS)

Cárdenas-González, M.; Osorio-Yáñez, C.; Gaspar-Ramírez, O.; Pavković, M.; Ochoa-Martínez, A.; López-Ventura, D.

2016-01-01

Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of exposure to environmental kidney toxicants with kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5–12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples had levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6 ppb) and chromium (61.7 ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467 pg/mL; T3: 615 pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/μl) and miR-423 (189 copies/μL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372 pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker to screen children for kidney damage induced by environmental toxic agents. - Highlights: • Children living in Mexico had exceedingly high arsenic and chromium exposure. • Arsenic and chromium exposure was significantly associated with urinary KIM-1. • KIM-1 might serve as a sensitive biomarker to evaluate kidney

Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1

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Cárdenas-González, M. [Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, Boston, MA (United States); Osorio-Yáñez, C. [Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (United States); Gaspar-Ramírez, O. [Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Unidad Noreste (CIATEJ), Nuevo Leon (Mexico); Pavković, M. [Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, Boston, MA (United States); Renal Division, Department of Medicine, Brigham and Women' s Hospital, Boston, MA (United States); Ochoa-Martínez, A. [Laboratorio de Toxicología Molecular, Centro de Investigación Aplicada en Ambiente y Salud (CIAAS), Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luis Potosí, San Luis Potosí (Mexico); López-Ventura, D. [Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), México City (Mexico); and others

2016-10-15

Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of exposure to environmental kidney toxicants with kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5–12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples had levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6 ppb) and chromium (61.7 ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467 pg/mL; T3: 615 pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/μl) and miR-423 (189 copies/μL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372 pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker to screen children for kidney damage induced by environmental toxic agents. - Highlights: • Children living in Mexico had exceedingly high arsenic and chromium exposure. • Arsenic and chromium exposure was significantly associated with urinary KIM-1. • KIM-1 might serve as a sensitive biomarker to evaluate kidney

Comparative proteomic analysis reveals heart toxicity induced by chronic arsenic exposure in rats.

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Huang, Qingyu; Xi, Guochen; Alamdar, Ambreen; Zhang, Jie; Shen, Heqing

2017-10-01

Arsenic is a widespread metalloid in the environment, which poses a broad spectrum of adverse effects on human health. However, a global view of arsenic-induced heart toxicity is still lacking, and the underlying molecular mechanisms remain unclear. By performing a comparative quantitative proteomic analysis, the present study aims to investigate the alterations of proteome profile in rat heart after long-term exposure to arsenic. As a result, we found that the abundance of 81 proteins were significantly altered by arsenic treatment (35 up-regulated and 46 down-regulated). Among these, 33 proteins were specifically associated with cardiovascular system development and function, including heart development, heart morphology, cardiac contraction and dilation, and other cardiovascular functions. It is further proposed that the aberrant regulation of 14 proteins induced by arsenic would disturb cardiac contraction and relaxation, impair heart morphogenesis and development, and induce thrombosis in rats, which is mediated by the Akt/p38 MAPK signaling pathway. Overall, these findings will augment our knowledge of the involved mechanisms and develop useful biomarkers for cardiotoxicity induced by environmental arsenic exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Historical cohort study of in utero exposure to uterotonic drugs and cognitive function in young adult life

DEFF Research Database (Denmark)

Sørensen, Henrik Toft; Rothman, Kenneth J.; Gillman, Matthew W.

1999-01-01

to the central nervous system.1 Several studies have reported an association between oxytocic drugs and neonatal hyperbilirubinaemia,2 which might influence long term cognitive function.3 Little is known, however, of the long term consequences of exposure to uterotonic drugs. We investigated whether in utero...

Ochratoxin A: In Utero Exposure in Mice Induces Adducts in Testicular DNA

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Jamie E. Jennings-Gee

2010-06-01

Full Text Available Ochratoxin A (OTA is a nephrotoxin and carcinogen that is associated with Balkan endemic nephropathy and urinary tract tumors. OTA crosses the placenta and causes adducts in the liver and kidney DNA of newborns. Because the testis and kidney develop from the same embryonic tissue, we reasoned that OTA also may cause adducts transplacentally in the testis. We tested the hypothesis that acute exposure to OTA, via food and via exposure in utero, causes adducts in testicular DNA and that these lesions are identical to those that can be produced in the kidney and testis by the consumption of OTA. Adult mice received a single dose of OTA (from 0–1,056 µg/kg by gavage. Pregnant mice received a single i.p. injection of OTA (2.5 mg/kg at gestation day 17. DNA adducts were determined by 32P-postlabeling. Gavage-fed animals sacrificed after 48 hours accumulated OTA in kidney and testis and showed DNA adducts in kidney and testis. Some OTA metabolites isolated from the tissues were similar in both organs (kidney and testis. The litters of mice exposed prenatally to OTA showed no signs of overt toxicity. However, newborn and 1-month old males had DNA adducts in kidney and testis that were chromatographically similar to DNA adducts observed in the kidney and testis of gavage-fed adults. One adduct was identified previously as C8-dG-OTA adduct by LC MS/MS. No adducts were observed in males from dams not exposed to OTA. Our findings that in utero exposure to OTA causes adducts in the testicular DNA of male offspring support a possible role for OTA in testicular cancer.

Contribution of breast milk and formula to arsenic exposure during the first year of life in a US prospective cohort.

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Carignan, Courtney C; Karagas, Margaret R; Punshon, Tracy; Gilbert-Diamond, Diane; Cottingham, Kathryn L

2016-09-01

Arsenic is a carcinogen that can also affect the cardiac, respiratory, neurological and immune systems. Children have higher dietary arsenic exposure than adults owing to their more restricted diets and greater intake per unit body mass. We evaluated the potential contributions of breast milk and formula to arsenic exposure throughout the first year of life for 356 infants in the prospective New Hampshire Birth Cohort Study (NHBCS) using infant diets reported by telephone at 4, 8 and 12 months of age; measured household water arsenic concentrations; and literature data. Based on our central-tendency models, population-wide geometric mean (GM) estimated arsenic exposures in the NHBCS were relatively low, decreasing from 0.1 μg/kg/day at 4 months of age to 0.07 μg/kg/day at 12 months of age. At all three time points, exclusively formula-fed infants had GM arsenic exposures ~8 times higher than exclusively breastfed infants owing to arsenic in both tap water and formula powder. Estimated maximum exposures reached 9 μg/kg/day among exclusively formula-fed infants in households with high tap water arsenic (80 μg/l). Overall, modeled arsenic exposures via breast milk and formula were low throughout the first year of life, unless formula was prepared with arsenic-contaminated tap water.

Timing of in utero malaria exposure influences fetal CD4 T cell regulatory versus effector differentiation

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Mary Prahl

2016-10-01

Full Text Available Abstract Background In malaria-endemic areas, the first exposure to malaria antigens often occurs in utero when the fetal immune system is poised towards the development of tolerance. Children exposed to placental malaria have an increased risk of clinical malaria in the first few years of life compared to unexposed children. Recent work has suggested the potential of pregnancy-associated malaria to induce immune tolerance in children living in malaria-endemic areas. A study was completed to evaluate the effect of malaria exposure during pregnancy on fetal immune tolerance and effector responses. Methods Using cord blood samples from a cohort of mother-infant pairs followed from early in pregnancy until delivery, flow cytometry analysis was completed to assess the relationship between pregnancy-associated malaria and fetal cord blood CD4 and dendritic cell phenotypes. Results Cord blood FoxP3+ Treg counts were higher in infants born to mothers with Plasmodium parasitaemia early in pregnancy (12–20 weeks of gestation; p = 0.048, but there was no association between Treg counts and the presence of parasites in the placenta at the time of delivery (by loop-mediated isothermal amplification (LAMP; p = 0.810. In contrast, higher frequencies of activated CD4 T cells (CD25+FoxP3−CD127+ were observed in the cord blood of neonates with active placental Plasmodium infection at the time of delivery (p = 0.035. This population exhibited evidence of effector memory differentiation, suggesting priming of effector T cells in utero. Lastly, myeloid dendritic cells were higher in the cord blood of infants with histopathologic evidence of placental malaria (p < 0.0001. Conclusion Together, these data indicate that in utero exposure to malaria drives expansion of both regulatory and effector T cells in the fetus, and that the timing of this exposure has a pivotal role in determining the polarization of the fetal immune response.

Relationship between long-term exposure to low-level arsenic in drinking water and the prevalence of abnormal blood pressure.

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Zhang, Chuanwu; Mao, Guangyun; He, Suxia; Yang, Zuopeng; Yang, Wei; Zhang, Xiaojing; Qiu, Wenting; Ta, Na; Cao, Li; Yang, Hui; Guo, Xiaojuan

2013-11-15

Arsenic increases the risk and incidence of cardiovascular disease. To explore the impact of long-term exposure to low-level arsenic in drinking water on blood pressure including pulse pressure (PP) and mean arterial blood pressure (MAP), a cross-sectional study was conducted in 2010 in which the blood pressure of 405 villagers was measured, who had been drinking water with an inorganic arsenic content 30-50 years of arsenic exposure and a 2.95-fold (95%CI: 1.31-6.67) increase in the group with >50 years exposure. Furthermore, the odds ratio for prevalence of abnormal PP and MAP were 1.06 (95%CI: 0.24-4.66) and 0.87 (95%CI: 0.36-2.14) in the group with >30-50 years of exposure, and were 2.46 (95%CI: 0.87-6.97) and 3.75 (95%CI: 1.61-8.71) for the group with >50 years exposure, compared to the group with arsenic exposure ≤ 30 years respectively. Significant trends for Hypertension (p<0.0001), PP (p<0.0001) and MAP (p=0.0016) were found. The prevalence of hypertension and abnormal PP as well as MAP is marked among a low-level arsenic exposure population, and significantly increases with the duration of arsenic exposure. Copyright © 2012 Elsevier B.V. All rights reserved.

Arsenic and human health effects: A review.

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Abdul, Khaja Shameem Mohammed; Jayasinghe, Sudheera Sammanthi; Chandana, Ediriweera P S; Jayasumana, Channa; De Silva, P Mangala C S

2015-11-01

Arsenic (As) is ubiquitous in nature and humans being exposed to arsenic via atmospheric air, ground water and food sources are certain. Major sources of arsenic contamination could be either through geological or via anthropogenic activities. In physiological individuals, organ system is described as group of organs that transact collectively and associate with other systems for conventional body functions. Arsenic has been associated with persuading a variety of complications in body organ systems: integumentary, nervous, respiratory, cardiovascular, hematopoietic, immune, endocrine, hepatic, renal, reproductive system and development. In this review, we outline the effects of arsenic on the human body with a main focus on assorted organ systems with respective disease conditions. Additionally, underlying mechanisms of disease development in each organ system due to arsenic have also been explored. Strikingly, arsenic has been able to induce epigenetic changes (in utero) and genetic mutations (a leading cause of cancer) in the body. Occurrence of various arsenic induced health effects involving emerging areas such as epigenetics and cancer along with their respective mechanisms are also briefly discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

In Utero Exposure to Compounds with Dioxin-like Activity and Birth Outcomes

DEFF Research Database (Denmark)

Vafeiadi, Marina; Agramunt, Silvia; Pedersen, Marie

2014-01-01

BACKGROUND: Maternal exposure to dioxins and dioxin-like compounds may affect fetal growth and development. We evaluated the association between in utero dioxin-like activity and birth outcomes in a prospective European mother-child study. METHODS: We measured dioxin-like activity in maternal...... and cord blood plasma samples collected at delivery using the Dioxin-Responsive Chemically Activated LUciferase eXpression (DR CALUX) bioassay in 967 mother-child pairs, in Denmark, Greece, Norway, Spain, and England. Multiple linear regression models were used to investigate the associations with birth...... weight, gestational age, and head circumference. RESULTS: Plasma dioxin-like activity was higher in maternal sample than in cord samples. Birth weight was lower with medium (-58 g [95% confidence interval (CI) = -176 to 62]) and high (-82 g [-216 to 53]) tertiles of exposure (cord blood) compared...

A biological indicator of inorganic arsenic exposure using the sum of urinary inorganic arsenic and monomethylarsonic acid concentrations

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Hata, Akihisa; Kurosawa, Hidetoshi; Endo, Yoko; Yamanaka, Kenzo; Fujitani, Noboru; Endo, Ginji

2016-01-01

Objectives: The sum of urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) concentrations is used for the biological monitoring of occupational iAs exposure. Although DMA is a major metabolite of iAs, it is an inadequate index because high DMA levels are present in urine after seafood consumption. We estimated the urinary iAs+MMA concentration corresponding to iAs exposure. Methods: We used data from two arsenic speciation analyses of urine samples from 330 Bangladeshi with oral iAs exposure and 172 Japanese workers without occupational iAs exposure using high-performance liquid chromatography with inductively coupled plasma mass spectrometry. Results: iAs, MMA, and DMA, but not arsenobetaine (AsBe), were detected in the urine of the Bangladeshi subjects. The correlation between iAs+MMA+DMA and iAs+MMA was obtained as log (iAs+MMA) = 1.038 log (iAs+MMA+DMA) -0.658. Using the regression formula, the iAs+MMA value was calculated as 2.15 and 7.5 μg As/l, corresponding to 3 and 10 μg As/m3 of exposures, respectively. In the urine of the Japanese workers, arsenic was mostly excreted as AsBe. We used the 95th percentile of iAs+MMA (12.6 μg As/l) as the background value. The sum of the calculated and background values can be used as a biological indicator of iAs exposure. Conclusion: We propose 14.8 and 20.1 μg As/l of urinary iAs+MMA as the biological indicators of 3 and 10 μg As/m3 iAs exposure, respectively. PMID:27010090

Low-level arsenic exposure via drinking water consumption and female fecundity - A preliminary investigation.

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Susko, Michele L; Bloom, Michael S; Neamtiu, Iulia A; Appleton, Allison A; Surdu, Simona; Pop, Cristian; Fitzgerald, Edward F; Anastasiu, Doru; Gurzau, Eugen S

2017-04-01

High level arsenic exposure is associated with reproductive toxicity in experimental and observational studies; however, few data exist to assess risks at low levels. Even less data are available to evaluate the impact of low level arsenic exposure on human fecundity. Our aim in this pilot study was a preliminary evaluation of associations between low level drinking water arsenic contamination and female fecundity. This retrospective study was conducted among women previously recruited to a hospital-based case-control study of spontaneous pregnancy loss in Timiṣ County, Romania. Women (n=94) with planned pregnancies of 5-20 weeks gestation completed a comprehensive physician-administered study questionnaire and reported the number of menstrual cycles attempting to conceive as the time to pregnancy (TTP). Drinking water samples were collected from residential drinking water sources and we determined arsenic levels using hydride generation-atomic absorption spectrometry (HG-AAS). Multivariable Cox-proportional hazards regression with Efron approximation was employed to evaluate TTP as a function of drinking water arsenic concentrations among planned pregnancies, adjusted for covariates. There was no main effect for drinking water arsenic exposure, yet the conditional probability for pregnancy was modestly lower among arsenic exposed women with longer TTPs, relative to women with shorter TTPs, and relative to unexposed women. For example, 1µg/L average drinking water arsenic conferred 5%, 8%, and 10% lower likelihoods for pregnancy in the 6th, 9th, and 12th cycles, respectively (P=0.01). While preliminary, our results suggest that low level arsenic contamination in residential drinking water sources may further impair fecundity among women with longer waiting times; however, this hypothesis requires confirmation by a future, more definitive study. Copyright © 2016 Elsevier Inc. All rights reserved.

Distribution and speciation of arsenic by transplacental and early life exposure to inorganic arsenic in offspring rats.

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Xi, Shuhua; Jin, Yaping; Lv, Xiuqiang; Sun, Guifan

2010-04-01

The amount of arsenic compounds was determined in the liver and brain of pups and in breast milk in the pup's stomach in relation to the route of exposure: transplacental, breast milk, or drinking water. Forty-eight pregnant rats were randomly divided into four groups, each group was given free access to drinking water that contained 0, 10, 50, and 100 mg/L NaAsO(2) from gestation day 6 (GD 6) until postnatal day 42 (PND 42). Once pups were weaned, they started to drink the same arsenic-containing water as the dams. Contents of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and trimethylarsenic acid (TMA) in livers and brains of the pups on PND 0, 15, 28, and 42 and breast milk taken from the pup's stomach on PND 0 and 15 were detected using the hydride generation atomic absorption spectroscopy method. Concentrations of iAs, MMA, and DMA in the breast milk, the brain, and the liver of the pups increased with the concentration of arsenic in drinking water on PND 0, 15, 28, and 42. Compared to the liver or brain, breast milk had the lowest arsenic concentrations. There was a significant decrease in the levels of arsenic species on PND 15 compared to PND 0, 28, or 42. It was confirmed that arsenic species can pass through the placental barrier from dams to offspring and across the blood-brain barrier in the pups, and breast milk from dams exposed to arsenic in drinking water contains less arsenic than the liver and brain of pups.

Historical cohort study of in utero exposure to uterotonic drugs and cognitive function in young adult life

DEFF Research Database (Denmark)

Sørensen, Henrik Toft; Steffensen, Flemming Hald; Sabroe, Svend

1999-01-01

Objective To examine whether in utero exposure to uterotonic drugs effects cognitive performance in draft-age men. Design Historical cohort study based on birth registry data and cognitive function measured during evaluations for military service. Subjects 4300 Danish conscripts born between 1973...... and those not exposed (n=3289), 43.1 versus 42.9 after adjustment for confounders. Conclusion Our data indicate that exposure to uterotonic drugs does not affect cognitive function 20 years later....

Arsenic exposure from drinking water is associated with decreased gene expression and increased DNA methylation in peripheral blood

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Ameer, Syeda Shegufta [Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund (Sweden); Engström, Karin [Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund (Sweden); Institute of Environmental Medicine, Unit of Metals & Health, Karolinska Institutet, Stockholm (Sweden); Hossain, Mohammad Bakhtiar [Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund (Sweden); Concha, Gabriela [Science Department, Risk Benefit Assessment Unit, National Food Agency, Uppsala (Sweden); Vahter, Marie [Institute of Environmental Medicine, Unit of Metals & Health, Karolinska Institutet, Stockholm (Sweden); Broberg, Karin, E-mail: Karin.broberg@ki.se [Institute of Environmental Medicine, Unit of Metals & Health, Karolinska Institutet, Stockholm (Sweden)

2017-04-15

Background: Exposure to inorganic arsenic increases the risk of cancer and non-malignant diseases. Inefficient arsenic metabolism is a marker for susceptibility to arsenic toxicity. Arsenic may alter gene expression, possibly by altering DNA methylation. Objectives: To elucidate the associations between arsenic exposure, gene expression, and DNA methylation in peripheral blood, and the modifying effects of arsenic metabolism. Methods: The study participants, women from the Andes, Argentina, were exposed to arsenic via drinking water. Arsenic exposure was assessed as the sum of arsenic metabolites in urine (U-As), using high performance liquid-chromatography hydride-generation inductively-coupled-plasma-mass-spectrometry, and arsenic metabolism efficiency was assessed by the urinary fractions (%) of the individual metabolites. Genome-wide gene expression (N = 80 women) and DNA methylation (N = 93; 80 overlapping with gene expression) in peripheral blood were measured using Illumina DirectHyb HumanHT-12 v4.0 and Infinium Human-Methylation 450K BeadChip, respectively. Results: U-As concentrations, ranging 10–1251 μg/L, was associated with decreased gene expression: 64% of the top 1000 differentially expressed genes were down-regulated with increasing U-As. U-As was also associated with hypermethylation: 87% of the top 1000 CpGs were hypermethylated with increasing U-As. The expression of six genes and six individual CpG sites were significantly associated with increased U-As concentration. Pathway analyses revealed enrichment of genes related to cell death and cancer. The pathways differed somewhat depending on arsenic metabolism efficiency. We found no overlap between arsenic-related gene expression and DNA methylation for individual genes. Conclusions: Increased arsenic exposure was associated with lower gene expression and hypermethylation in peripheral blood, but with no evident overlap. - Highlights: • Women exposed to inorganic arsenic were studied for

A review of the epidemiologic literature on the role of environmental arsenic exposure and cardiovascular diseases

International Nuclear Information System (INIS)

Wang, C.-H.; Hsiao, C.K.; Chen, C.-L.; Hsu, L.-I; Chiou, H.-Y.; Chen, S.-Y.; Hsueh, Y.-M.; Wu, M.-M.; Chen, C.-J.

2007-01-01

Cardiovascular disease is the leading cause of mortality worldwide. Arsenic is a ubiquitous metalloid in the crust of the earth. Chronic arsenic poisoning is becoming an emerging epidemic in Asia. Epidemiological studies have shown that chronic arsenic poisoning through ingestion of arsenic-contaminated water is associated with various cardiovascular diseases in dose-response relationships. These cardiovascular disorders include carotid atherosclerosis detected by ultrasonography, impaired microcirculation, prolonged QT interval and increased QT dispersion in electrocardiography, and clinical outcomes such as hypertension, blackfoot disease (a unique peripheral vascular disease endemic in southwestern Taiwan), coronary artery disease and cerebral infarction. Chronic arsenic poisoning is an independent risk factor for cardiovascular disease. The adverse cardiovascular effects of long-term arsenic exposure may be persistent and/or irreversible. Arsenic-induced cardiovascular diseases in human population may result from the interaction among genetic, environment and nutritional factors. The major adverse cardiovascular effect of chronic arsenic poisoning has been established qualitatively and quantitatively in the high arsenic exposure areas, but the low-dose effect of arsenic on cardiovascular diseases remains to be explored. Cardiovascular death is the major cause of mortality worldwide, and a small increased risk may imply a large quantity of excess mortality

Arsenic species in wheat, raw and cooked rice: Exposure and associated health implications.

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Rasheed, Hifza; Kay, Paul; Slack, Rebecca; Gong, Yun Yun

2018-09-01

Arsenic concentrations above 10μgL -1 were previously found in 89% of ground water sources in six villages of Pakistan. The present study has ascertained the health risks associated with exposure to total arsenic (tAs) and its species in most frequently consumed foods. Inorganic arsenic (iAs) concentrations were found to be 92.5±41.88μgkg -1 , 79.21±76.42μgkg -1 , and 116.38±51.38μgkg -1 for raw rice, cooked rice and wheat respectively. The mean tAs concentrations were 47.47±30.72μgkg -1 , 71.65±74.7μgkg -1 , 105±61.47μgkg -1 . Wheat is therefore demonstrated to be a significant source of arsenic exposure. Dimethylarsinic acid was the main organic species detected in rice, whilst monomethylarsonic acid was only found at trace levels. Total daily intake of iAs exceeded the provisional tolerable daily intake of 2.1μgkg -1 day -1 body weight in 74% of study participants due to concurrent intake from water (94%), wheat (5%) and raw rice (1%). A significant association between tAs in cooked rice and cooking water resulted in tAs intake 43% higher in cooked rice compared to raw rice. The study suggests that arsenic intake from food, particularly from wheat consumption, holds particular significance where iAs is relatively low in water. Chronic health risks were found to be significantly higher from wheat intake than rice, whilst the risk in terms of acute effects was below the USEPA's limit of 1.0. Children were at significantly higher health risk than adults due to iAs exposure from rice and/or wheat. The dietary exposure of participants to tAs was attributable to staple food intake with ground water iAs iAs in drinking water. Although the daily iAs intake from food was lower than total water intake, the potential health risk from exposure to arsenic and its species still exists and requires exposure control measures. Copyright © 2018 Elsevier B.V. All rights reserved.

Arsenic drinking water exposure and urinary excretion among adults in the Yaqui Valley, Sonora, Mexico

International Nuclear Information System (INIS)

Meza, M.M.; Kopplin, M.J.; Burgess, J.L.; Gandolfi, A.J.

2004-01-01

The objective of this study was to determine arsenic exposure via drinking water and to characterize urinary arsenic excretion among adults in the Yaqui Valley, Sonora, Mexico. A cross-sectional study was conducted from July 2001 to May 2002. Study subjects were from the Yaqui Valley, Sonora, Mexico, residents of four towns with different arsenic concentrations in their drinking water. Arsenic exposure was estimated through water intake over 24 h. Arsenic excretion was assessed in the first morning void urine. Total arsenic concentrations and their species arsenate (As V), arsenite (As III), monomethyl arsenic (MMA), and dimethyl arsenic (DMA) were determined by HPLC/ICP-MS. The town of Esperanza with the highest arsenic concentration in water had the highest daily mean intake of arsenic through drinking water, the mean value was 65.5 μg/day. Positive correlation between total arsenic intake by drinking water/day and the total arsenic concentration in urine (r=0.50, P<0.001) was found. Arsenic excreted in urine ranged from 18.9 to 93.8 μg/L. The people from Esperanza had the highest geometric mean value of arsenic in urine, 65.1 μg/L, and it was statistically significantly different from those of the other towns (P<0.005). DMA was the major arsenic species in urine (47.7-67.1%), followed by inorganic arsenic (16.4-25.4%), and MMA (7.5-15%). In comparison with other reports the DMA and MMA distribution was low, 47.7-55.6% and 7.5-9.7%, respectively, in the urine from the Yaqui Valley population (except the town of Cocorit). The difference in the proportion of urinary arsenic metabolites in those towns may be due to genetic polymorphisms in the As methylating enzymes of these populations

Arsenic drinking water exposure and urinary excretion among adults in the Yaqui Valley, Sonora, Mexico.

Science.gov (United States)

Meza, Maria Mercedes; Kopplin, Michael J; Burgess, Jefferey L; Gandolfi, A Jay

2004-10-01

The objective of this study was to determine arsenic exposure via drinking water and to characterize urinary arsenic excretion among adults in the Yaqui Valley, Sonora, Mexico. A cross-sectional study was conducted from July 2001 to May 2002. Study subjects were from the Yaqui Valley, Sonora, Mexico, residents of four towns with different arsenic concentrations in their drinking water. Arsenic exposure was estimated through water intake over 24 h. Arsenic excretion was assessed in the first morning void urine. Total arsenic concentrations and their species arsenate (As V), arsenite (As III), monomethyl arsenic (MMA), and dimethyl arsenic (DMA) were determined by HPLC/ICP-MS. The town of Esperanza with the highest arsenic concentration in water had the highest daily mean intake of arsenic through drinking water, the mean value was 65.5 microg/day. Positive correlation between total arsenic intake by drinking water/day and the total arsenic concentration in urine (r = 0.50, P < 0.001) was found. Arsenic excreted in urine ranged from 18.9 to 93.8 microg/L. The people from Esperanza had the highest geometric mean value of arsenic in urine, 65.1 microg/L, and it was statistically significantly different from those of the other towns (P < 0.005). DMA was the major arsenic species in urine (47.7-67.1%), followed by inorganic arsenic (16.4-25.4%), and MMA (7.5-15%). In comparison with other reports the DMA and MMA distribution was low, 47.7-55.6% and 7.5-9.7%, respectively, in the urine from the Yaqui Valley population (except the town of Cocorit). The difference in the proportion of urinary arsenic metabolites in those towns may be due to genetic polymorphisms in the As methylating enzymes of these populations.

HPLC-ICP-MS speciation analysis of arsenic in urine of Japanese subjects without occupational exposure.

Science.gov (United States)

Hata, Akihisa; Endo, Yoko; Nakajima, Yoshiaki; Ikebe, Maiko; Ogawa, Masanori; Fujitani, Noboru; Endo, Ginji

2007-05-01

The toxicity and carcinogenicity of arsenic depend on its species. Individuals living in Japan consume much seafood that contains high levels of organoarsenics. Speciation analysis of urinary arsenic is required to clarify the health risks of arsenic intake. There has been no report of urinary arsenic analysis in Japan using high performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC-ICP-MS). We performed speciation analysis of urinary arsenic for 210 Japanese male subjects without occupational exposure using HPLC-ICP-MS. The median values of urinary arsenics were as follows: sodium arsenite (AsIII), 3.5; sodium arsenate (AsV), 0.1; monomethylarsonic acid (MMA), 3.1; dimethylarsinic acid (DMA), 42.6; arsenobetaine (AsBe), 61.3; arsenocholine, trimethylarsine oxide, and unidentified arsenics (others), 5.2; and total arsenic (total As), 141.3 microgAs/l. The median creatinine-adjusted values were as follows: AsIII, 3.0; AsV, 0.1; MMA, 2.6; DMA, 35.9; AsBe, 52.1; others 3.5; and total As, 114.9 microgAs/g creatinine. Our findings indicate that DMA and AsBe levels in Japan are much higher than those found in Italian and American studies. It appears that the high levels of DMA and AsBe observed in Japan may be due in part to seafood intake. ACGIH and DFG set the BEI and BAT values for occupational arsenic exposure as 35 microgAs/l and 50 microgAs/l, respectively, using the sum of inorganic arsenic (iAs), MMA, and DMA. In the general Japanese population, the sums of these were above 50 microgAs/l in 115 (55%) samples. We therefore recommend excluding DMA concentration in monitoring of iAs exposure.

Diffuse parenchymal lung disease in a case of chronic arsenic exposure

Directory of Open Access Journals (Sweden)

Somnath Bhattacharya

2016-01-01

Full Text Available A 42-year-old housewife, the resident of rural part of West Bengal, presented with gradually progressive exertional dyspnea associated with a dry cough for last 3 years clinical features were suggestive of diffuse parenchymal lung disease (DPLD. Her chest X-ray posteroanterior view and high resolution computed tomography scan of the thorax showed bilateral patchy ground glass opacities and reticulonodular pattern. Search for the etiology revealed classical skin findings of chronic arsenic exposure in the form of generalized darkening and thickening of skin and keratotic lesions over the palms and soles and classical raindrop pigmentation over leg which was present for last 7 years subsequently her bronchoalveolar lavage fluid, hair, nail, and drinking water showed significant amount of arsenic contamination. By exclusion of all known causes of DPLD, we concluded that it was a case of DPLD due to chronic arsenic exposure. To the best of our knowledge, only few case report of DPLD in chronic arsenicosis has been reported till date.

Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

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Qu, Wei, E-mail: qu@niehs.nih.gov; Waalkes, Michael P.

2015-02-01

We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO{sub 2}) was less cytolethal over 24 h in WT cells (LC{sub 50} = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC{sub 50} = 5.6 ± 1.2 μM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 μM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% and 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTα2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. - Highlights: • Metallothionein blocks arsenic toxicity. • Metallothionein reduces arsenic-induced DNA damage. • Metallothionein may bind arsenic or radicals produced by arsenic.

Arsenic induced apoptosis in rat liver following repeated 60 days exposure

International Nuclear Information System (INIS)

Bashir, Somia; Sharma, Yukti; Irshad, M.; Nag, T.C.; Tiwari, Monica; Kabra, M.; Dogra, T.D.

2006-01-01

Background: Accumulation of the wide spread environmental toxin arsenic in liver results in hepatotoxcity. Exposure to arsenite and other arsenicals has been previously shown to induce apoptosis in certain tumor cell lines at low (1-3 μM) concentration. Aim: The present study was focused to elucidate the role of free radicals in arsenic toxicity and to investigate the nature of in vivo sodium arsenite induced cell death in liver. Methods: Male wistar rats were exposed to arsenite at three different doses of 0.05, 2.5 and 5 mg/l for 60 days. Oxidative stress in liver was measured by estimating pro-oxidant and antioxidant activity in liver. Histopathological examination of liver was carried out by light and transmission electron microscopy. Analysis of DNA fragmentation by gel electrophoresis was used to identify apoptosis after the exposure. Terminal deoxy-nucleotidyl transferase mediated dUTP Nick end-labeling (TUNEL) assay was used to qualify and quantify apoptosis. Results: A significant increase in cytochrome-P450 and lipid peroxidation accompanied with a significant alteration in the activity of many of the antioxidants was observed, all suggestive of arsenic induced oxidative stress. Histopathological examination under light and transmission electron microscope suggested a combination of ongoing necrosis and apoptosis. DNA-TUNEL showed an increase in apoptotic cells in liver. Agarose gel electrophoresis of DNA of hepatocytes resulted in a characteristic ladder pattern. Conclusion: Chronic arsenic administration induces a specific pattern of apoptosis called post-mitotic apoptosis

Clinical findings on in utero exposed microcephalic children

Energy Technology Data Exchange (ETDEWEB)

Tabuchi, Akira; Hirai, Tsuyoshi; Nakagawa, Shigeru; Shimada, Katsunobu; Fujito, Junro

1966-12-24

Since animal experiments have shown that microcephaly is induced by fetal exposure to radiation and microcephaly has been found in children of mothers exposed to x-ray therapy during pregnancy (Murphy et al), the main cause of microcephaly in children exposed in utero to the A-bomb is considered to be ionizing radiation. Wood et al reported the increased incidence of microcephaly and mental retardation in children exposed in utero at proximal distances which they felt could not be attributed to any other known variable. ABCC has recently concluded that the effect of in utero exposure is primarily due to the immediate effect of radiation upon the fetuses although in A-bomb exposure the physical injury to the mother due to the A-bomb cannot be completely ignored. Our survey likewise revealed an increase of microcephaly in children exposed early in pregnancy at less than 15 weeks at closer distances than 1500 m. Thus, we presume that A-bomb radiation increases the incidence of microcephaly. 16 references, 8 tables.

Total arsenic concentrations in toenails quantified by two techniques provide a useful biomarker of chronic arsenic exposure in drinking water

International Nuclear Information System (INIS)

Adair, Blakely M.; Hudgens, Edward E.; Schmitt, Michael T.; Calderon, Rebecca L.; Thomas, David J.

2006-01-01

Accurate quantitation of any contaminant of interest is critical for exposure assessment and metabolism studies that support risk assessment. A preliminary step in an arsenic exposure assessment study in Nevada quantified total arsenic (TAs) concentrations in tissues as biomarkers of exposure. Participants in this study (n=95) were at least 45 years old, had lived in the area for more than 20 years, and were exposed to a wide range of arsenic concentrations in drinking water (3-2100ppb). Concentrations of TAs in blood, urine, and toenails determined by hydride generation-atomic fluorescence spectrometry (HG-AFS) ranged from below detection to 0.03, 0.76, and 12ppm, respectively; TAs in blood rarely exceeded the limit of detection. For comparison, TAs in toenails determined by neutron activation analysis (NAA) ranged from below detection to 16ppm. Significant (P 2 =0.3557 HG-AFS, adjusted r 2 =0.3922 NAA); TAs concentrations in urine were not described by drinking water As (adjusted r 2 =0.0170, P=0.1369). Analyses of TAs in toenails by HGAFS and NAA yielded highly concordant estimates (r=0.7977, P<0.0001). These results suggest that toenails are a better biomarker of chronic As exposure than urine in the current study, because the sequestration of As in toenails provides an integration of exposure over time that does not occur in urine

Maternal exposure to arsenic, cadmium, lead, and mercury and neural tube defects in offspring

International Nuclear Information System (INIS)

Brender, Jean D.; Suarez, Lucina; Felkner, Marilyn; Gilani, Zunera; Stinchcomb, David; Moody, Karen; Henry, Judy; Hendricks, Katherine

2006-01-01

Arsenic, cadmium, lead, and mercury are neurotoxins, and some studies suggest that these elements might also be teratogens. Using a case-control study design, we investigated the relation between exposure to these heavy metals and neural tube defects (NTDs) in offspring of Mexican-American women living in 1 of the 14 Texas counties bordering Mexico. A total of 184 case-women with NTD-affected pregnancies and 225 control-women with normal live births were interviewed about their environmental and occupational exposures during the periconceptional period. Biologic samples for blood lead and urinary arsenic, cadmium, and mercury were also obtained for a subset of these women. Overall, the median levels of these biomarkers for heavy metal exposure did not differ significantly (P>0.05) between case- and control-women. However, among women in the highest income group, case-women were nine times more likely (95% confidence interval (CI) 1.4-57) than control-women to have a urinary mercury >=5.62μg/L. Case-women were 4.2 times more likely (95% CI 1.1-16) to report burning treated wood during the periconceptional period than control-women. Elevated odds ratios (ORs) were observed for maternal and paternal occupational exposures to arsenic and mercury, but the 95% CIs were consistent with unity. The 95% CIs of the ORs were also consistent with unity for higher levels of arsenic, cadmium, lead, and mercury in drinking water and among women who lived within 2 miles at the time of conception to industrial facilities with reported emissions of any of these heavy metals. Our findings suggest that maternal exposures to arsenic, cadmium, or lead are probably not significant risk factors for NTDs in offspring. However, the elevated urinary mercury levels found in this population and exposures to the combustion of treated wood may warrant further investigation

In-utero exposure to smoking, alcohol, coffee, and tea and risk of strabismus

DEFF Research Database (Denmark)

Torp-Pedersen, Tobias; Boyd, Heather A; Poulsen, Gry

2010-01-01

.92, 1.61). Light maternal alcohol consumption was inversely associated with strabismus risk, whereas maternal coffee and tea drinking were not associated with strabismus risk. In conclusion, smoking during pregnancy is associated with an increased risk of strabismus in the offspring. Conversely, light......In a prospective, population-based cohort study, the authors investigated the effect of in-utero exposure to maternal smoking and consumption of alcohol, coffee, and tea on the risk of strabismus. They reviewed medical records for children in the Danish National Birth Cohort identified through...... alcohol consumption is associated with decreased risk....

Association of soil arsenic and nickel exposure with cancer mortality rates, a town-scale ecological study in Suzhou, China.

Science.gov (United States)

Chen, Kai; Liao, Qi Lin; Ma, Zong Wei; Jin, Yang; Hua, Ming; Bi, Jun; Huang, Lei

2015-04-01

Heavy metals and arsenic are well-known carcinogens. However, few studies have examined whether soil heavy metals and arsenic concentrations associate with cancer in the general population. In this ecological study, we aimed to evaluate the association of heavy metals and arsenic in soil with cancer mortality rates during 2005-2010 in Suzhou, China, after controlling for education and smoking prevalence. In 2005, a total of 1683 soil samples with a sampling density of one sample every 4 km(2) were analyzed. Generalized linear model with a quasi-Poisson regression was applied to evaluate the association between town-scale cancer mortality rates and soil heavy metal concentrations. Results showed that soil arsenic exposure had a significant relationship with colon, gastric, kidney, lung, and nasopharyngeal cancer mortality rates and soil nickel exposure was significantly associated with liver and lung cancer. The associations of soil arsenic and nickel exposure with colon, gastric, kidney, and liver cancer in male were higher than those in female. The observed associations of soil arsenic and nickel with cancer mortality rates were less sensitive to alternative exposure metrics. Our findings would contribute to the understanding of the carcinogenic effect of soil arsenic and nickel exposure in general population.

Probabilistic Risk Assessment of Cancer from Exposure Inorganic Arsenic in Duplicate Food by Villagers in Ronphibun, Thailand

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Piyawat Saipan

2010-07-01

Full Text Available Ronphibun district is a district in Nakorn Si Thammarat province, within southern Thailand. This district is the site of several former tin mines that were in operation 100 years ago. Arsenic contamination caused by past mining activities remains in the area. The specific purpose of this study was conducted to assess cancer risk in people living within Ronphibun district from exposure to inorganic arsenic via duplicate food using probabilistic risk assessment. A hundred and fifty duplicate food samples were collected from participants. Inorganic arsenic concentrations are determined by hydride generation atomic absorption spectrometry. Inorganic arsenic concentrations in duplicate food ranged from 0.16 to 0.42 μg/g dry weight. The probabilistic carcinogenic risk levels were 6.76 x 10-4 and 1.74 x 10-3 based on the 50th and 95th percentile, respectively. Risk values for people in Ronphibun from exposure to inorganic arsenic remained higher than the acceptable target risk. Sensitivity analysis indicted that exposure duration and concentrations of arsenic in food were the two most influential of cancer risk estimates.

On the mechanism of induction of congenital nervous and imune deficienies in new borns resulting from exposure to radiation and other factors in utero theoretical analysis

International Nuclear Information System (INIS)

Filyushkin, I.V.

1993-01-01

Proposed is a mechanism through which exposure in utero to deleterious agents (including radiation) induces hereditary nervous (and immune) deficiencies in newborns. This mechanism was found theoretically in the framework of multidisciplinary analysis of neuroimmunoendocrine reactivity development peculiar to normal embryogenesis in comparison to that under in utero exposure. Found systemic mechanism accounts induced neural (and or) immune reactivity dificiencies on the response of embryonic homeostasis to effects of radiation or any other deleterious agent on growth potencies of embryo cells

Synergistic effect of polymorphisms of paraoxonase gene cluster and arsenic exposure on electrocardiogram abnormality

International Nuclear Information System (INIS)

Liao, Y.-T.; Li, W.-F.; Chen, C.-J.; Prineas, Ronald J.; Chen, Wei J.; Zhang Zhuming; Sun, C.-W.; Wang, S.-L.

2009-01-01

Arsenic has been linked to increased prevalence of cancer and cardiovascular disease (CVD), but the long-term impact of arsenic exposure remains unclear. Human paraoxonase (PON1) is a high-density lipoprotein-associated antioxidant enzyme which hydrolyzes oxidized lipids and is thought to be protective against atherosclerosis, but evidence remains limited to case-control studies. Only recently have genes encoding enzymes responsible for arsenic metabolism, such as AS3MT and GSTO, been cloned and characterized. This study was designed to evaluate the synergistic interaction of genetic factors and arsenic exposure on electrocardiogram abnormality. A total of 216 residents from three tap water implemented villages of previous arseniasis-hyperendemic regions in Taiwan were prospectively followed for an average of 8 years. For each resident, a 12-lead conventional electrocardiogram (ECG) was recorded and coded by Minnesota Code standard criteria. Eight functional polymorphisms of PON1, PON2, AS3MT, GSTO1, and GSTO2 were examined for genetic susceptibility to ECG abnormality. Among 42 incident cases with ECG deterioration identified among 121 baseline-normal subjects, arsenic exposure was significantly correlated with incidence of ECG abnormality. In addition, polymorphisms in two paraoxonase genes were also found associated with the incidence of ECG abnormality. A haplotype R-C-S constituted by polymorphisms of PON1 Q192R, -108C/T and PON2 C311S was linked to the increased risk. Subjects exposed to high levels of As (cumulative As exposure > 14.7 ppm-year or drinking artesian well water > 21 years) and carrying the R-C-S haplotype had significantly increased risks for ECG abnormality over those with only one risk factor. Results of this study showed a long-term arsenic effect on ECG abnormality and significant gene-gene and gene-environment interactions linked to the incidence of CVD. This finding might have important implications for a novel and potentially useful

Why Does Exposure to Arsenic from Drinking Groundwater in Asian Megadeltas Continue to be High?

Science.gov (United States)

van Geen, A.; Ahmed, K. M.; Ahmed, E. B.; Choudhury, I.; Mozumder, M. R. H.; Bostick, B. C.; Mailloux, B. J.; Knappett, P. S.; Schlosser, P.

2014-12-01

Concentrations of arsenic in groundwater pumped from a significant fraction of the millions of shallow tubewells installed, mostly privately, across S/SE Asia exceed the WHO guideline value of 10 ug/L by a factor of 10 to 100. The resulting exposure has been linked to cancers and cardio-vascular disease in adults and inhibited intellectual function in children. In Bangladesh, the most affected country, the impact of early mitigation efforts relying on water treatment has been limited by the cost and logistics of maintenance. A simpler approach based on switching human consumption to low-arsenic wells has proved to be more resilient although it remains far from sufficiently adopted. A decade ago, there was concern that low-arsenic wells might become contaminated upon use. Observations and modeling have since shown that groundwater arsenic concentrations are likely to rise only in certain hydrogeologically vulnerable areas and then only gradually. Our recently completed blanket-testing campaign of 50,000 wells in 300 villages of Bangladesh has shown that, instead, a leading cause of current exposure is that households have continued to install wells and typically have nowhere to turn for a reliable arsenic test. The same campaign has shown that another reason for continued exposure is that deeper wells that are low in arsenic and whose installation has been subsidized by the Bangladesh government are not located to maximize public access. The geographic clustering of these deep wells suggests that, all too often, their location is decided on the basis of political allegiance rather than need. Such obstacles to lowering arsenic exposure might be overcome with more widespread testing and the public posting of maps of test results also showing where deep wells have been installed. We will show that obtaining and sharing such information has been greatly facilitated by a reliable field-kit for arsenic and the increasing use of smartphones in Bangladesh.

Characterizing arsenic in preserved hair for assessing exposure potential and discriminating poisoning

Energy Technology Data Exchange (ETDEWEB)

Kempson, Ivan M.; Henry, Dermot; Francis, James; (Museum Vic.); (U. South Australia); (UWO)

2009-05-21

Advanced analytical techniques have been used to characterize arsenic in taxidermy specimens. Arsenic was examined to aid in discriminating its use as a preservative from that incorporated by ingestion and hence indicate poisoning (in the case of historical figures). The results are relevant to museum curators, occupational and environmental exposure concerns, toxicological and anthropological investigations. Hair samples were obtained from six taxidermy specimens preserved with arsenic in the late 1800s and early 1900s to investigate the arsenic incorporation. The presence of arsenic poses a potential hazard in museum and private collections. For one sample, arsenic was confirmed to be present on the hair with time-of-flight secondary ion mass spectrometry and then measured with neutron activation analysis to comprise 176 {mu}g g{sup -1}. The hair cross section was analysed with synchrotron micro-X-ray fluorescence to investigate the transverse distribution of topically applied arsenic. It was found that the arsenic had significantly penetrated all hair samples. Association with melanin clusters and the medulla was observed. Lead and mercury were also identified in one sample. X-ray absorption near-edge spectroscopy of the As K-edge indicated that an arsenate species predominantly existed in all samples; however, analysis was hindered by very rapid photoreduction of the arsenic. It would be difficult to discriminate arsenic consumption from topically applied arsenic based on the physical transverse distribution. Longitudinal distributions and chemical speciation may still allow differentiation.

Arsenic-Induced Genotoxicity and Genetic Susceptibility to Arsenic-Related Pathologies

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Fabrizio Bianchi

2013-04-01

Full Text Available The arsenic (As exposure represents an important problem in many parts of the World. Indeed, it is estimated that over 100 million individuals are exposed to arsenic, mainly through a contamination of groundwaters. Chronic exposure to As is associated with adverse effects on human health such as cancers, cardiovascular diseases, neurological diseases and the rate of morbidity and mortality in populations exposed is alarming. The purpose of this review is to summarize the genotoxic effects of As in the cells as well as to discuss the importance of signaling and repair of arsenic-induced DNA damage. The current knowledge of specific polymorphisms in candidate genes that confer susceptibility to arsenic exposure is also reviewed. We also discuss the perspectives offered by the determination of biological markers of early effect on health, incorporating genetic polymorphisms, with biomarkers for exposure to better evaluate exposure-response clinical relationships as well as to develop novel preventative strategies for arsenic- health effects.

Acetylated H4K16 by MYST1 protects UROtsa cells from arsenic toxicity and is decreased following chronic arsenic exposure

International Nuclear Information System (INIS)

Jo, William Jaime; Ren, Xuefeng; Chu, Feixia; Aleshin, Maria; Wintz, Henri; Burlingame, Alma; Smith, Martyn Thomas; Vulpe, Chris Dillon; Zhang Luoping

2009-01-01

Arsenic, a human carcinogen that is associated with an increased risk of bladder cancer, is commonly found in drinking water. An important mechanism by which arsenic is thought to be carcinogenic is through the induction of epigenetic changes that lead to aberrant gene expression. Previously, we reported that the SAS2 gene is required for optimal growth of yeast in the presence of arsenite (As III ). Yeast Sas2p is orthologous to human MYST1, a histone 4 lysine 16 (H4K16) acetyltransferase. Here, we show that H4K16 acetylation is necessary for the resistance of yeast to As III through the modulation of chromatin state. We further explored the role of MYST1 and H4K16 acetylation in arsenic toxicity and carcinogenesis in human bladder epithelial cells. The expression of MYST1 was knocked down in UROtsa cells, a model of bladder epithelium that has been used to study arsenic-induced carcinogenesis. Silencing of MYST1 reduced acetylation of H4K16 and induced sensitivity to As III and to its more toxic metabolite monomethylarsonous acid (MMA III ) at doses relevant to high environmental human exposures. In addition, both As III and MMA III treatments decreased global H4K16 acetylation levels in a dose- and time-dependent manner. This indicates that acetylated H4K16 is required for resistance to arsenic and that a reduction in its levels as a consequence of arsenic exposure may contribute to toxicity in UROtsa cells. Based on these findings, we propose a novel role for the MYST1 gene in human sensitivity to arsenic.

Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

International Nuclear Information System (INIS)

Ren, Xuefeng; Gaile, Daniel P.; Gong, Zhihong; Qiu, Wenting; Ge, Yichen; Zhang, Chuanwu; Huang, Chenping; Yan, Hongtao; Olson, James R.; Kavanagh, Terrance J.; Wu, Hongmei

2015-01-01

Arsenic exposure is postulated to modify microRNA (miRNA) expression, leading to changes of gene expression and toxicities, but studies relating the responses of miRNAs to arsenic exposure are lacking, especially with respect to in vivo studies. We utilized high-throughput sequencing technology and generated miRNA expression profiles of liver tissues from Sprague Dawley (SD) rats exposed to various concentrations of sodium arsenite (0, 0.1, 1, 10 and 100 mg/L) for 60 days. Unsupervised hierarchical clustering analysis of the miRNA expression profiles clustered the SD rats into different groups based on the arsenic exposure status, indicating a highly significant association between arsenic exposure and cluster membership (p-value of 0.0012). Multiple miRNA expressions were altered by arsenic in an exposure concentration-dependent manner. Among the identified arsenic-responsive miRNAs, several are predicted to target Nfe2l2-regulated antioxidant genes, including glutamate–cysteine ligase (GCL) catalytic subunit (GCLC) and modifier subunit (GCLM) which are involved in glutathione (GSH) synthesis. Exposure to low concentrations of arsenic increased mRNA expression for Gclc and Gclm, while high concentrations significantly reduced their expression, which were correlated to changes in hepatic GCL activity and GSH level. Moreover, our data suggested that other mechanisms, e.g., miRNAs, rather than Nfe2l2-signaling pathway, could be involved in the regulation of mRNA expression of Gclc and Gclm post-arsenic exposure in vivo. Together, our findings show that arsenic exposure disrupts the genome-wide expression of miRNAs in vivo, which could lead to the biological consequence, such as an altered balance of antioxidant defense and oxidative stress. - Highlights: • Chronic arsenic exposure induces changes of hepatic miRNA expression profiles. • Hepatic GCL activity and GSH level in rats are altered following arsenic exposure. • Arsenic induced GCL expression change is

Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

Energy Technology Data Exchange (ETDEWEB)

Ren, Xuefeng, E-mail: xuefengr@buffalo.edu [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Department of Pharmacology and Toxicology, School of Biomedical Sciences, The State University of New York, Buffalo, NY 14214 (United States); Gaile, Daniel P. [Department of Biostatistics, School of Public Health and Health Professions, the State University of New York, Buffalo, NY 14214 (United States); Gong, Zhihong [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Qiu, Wenting [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Ge, Yichen [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Zhang, Chuanwu; Huang, Chenping; Yan, Hongtao [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Olson, James R. [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Department of Pharmacology and Toxicology, School of Biomedical Sciences, The State University of New York, Buffalo, NY 14214 (United States); Kavanagh, Terrance J. [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195 (United States); Wu, Hongmei, E-mail: hongmeiwwu@hotmail.com [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China)

2015-03-15

Arsenic exposure is postulated to modify microRNA (miRNA) expression, leading to changes of gene expression and toxicities, but studies relating the responses of miRNAs to arsenic exposure are lacking, especially with respect to in vivo studies. We utilized high-throughput sequencing technology and generated miRNA expression profiles of liver tissues from Sprague Dawley (SD) rats exposed to various concentrations of sodium arsenite (0, 0.1, 1, 10 and 100 mg/L) for 60 days. Unsupervised hierarchical clustering analysis of the miRNA expression profiles clustered the SD rats into different groups based on the arsenic exposure status, indicating a highly significant association between arsenic exposure and cluster membership (p-value of 0.0012). Multiple miRNA expressions were altered by arsenic in an exposure concentration-dependent manner. Among the identified arsenic-responsive miRNAs, several are predicted to target Nfe2l2-regulated antioxidant genes, including glutamate–cysteine ligase (GCL) catalytic subunit (GCLC) and modifier subunit (GCLM) which are involved in glutathione (GSH) synthesis. Exposure to low concentrations of arsenic increased mRNA expression for Gclc and Gclm, while high concentrations significantly reduced their expression, which were correlated to changes in hepatic GCL activity and GSH level. Moreover, our data suggested that other mechanisms, e.g., miRNAs, rather than Nfe2l2-signaling pathway, could be involved in the regulation of mRNA expression of Gclc and Gclm post-arsenic exposure in vivo. Together, our findings show that arsenic exposure disrupts the genome-wide expression of miRNAs in vivo, which could lead to the biological consequence, such as an altered balance of antioxidant defense and oxidative stress. - Highlights: • Chronic arsenic exposure induces changes of hepatic miRNA expression profiles. • Hepatic GCL activity and GSH level in rats are altered following arsenic exposure. • Arsenic induced GCL expression change is

Sex steroid hormone levels and reproductive development of eight-year-old children following in utero and environmental exposure to phthalates.

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Pen-Hua Su

Full Text Available In utero exposure to phthalates may adversely affect reproductive development in children due to the anti-androgenic properties of the pthalates. Accordingly, we aimed to determine the effects of in utero and environmental phthalate exposure on the reproductive development of eight-year-old children. We recruited 180 children in central Taiwan during November 2001 and followed them until August 2009 when all children became eight years old. Birth outcomes were collected. Bone age, hormone concentrations, and reproductive developmental stages were determined. Phthalate metabolite levels, including mono-2-ethylhexyl phthalate [MEHP], mono-n-butyl phthalate [MnBP], and mono-benzyl phthalate [MBzP], were assessed. No significant gender differences were found in in utero phthalate exposure. Maternal urinary levels of phthalate metabolites did not correlate significantly with birth outcomes, physical characteristics, and reproductive hormones of the eight-year-old children. Regarding the urinary phthalate metabolite levels of the eight-year-old children, MEHP correlated significantly with serum progesterone levels. MEHP levels in girls correlated significantly with serum progesterone levels. MnBP correlated significantly with serum FSH in all children. In girls, MnBP correlated with serum FSH, and MBzP correlated with serum progesterone and FSH levels. Urinary phthalate metabolite levels did not correlate with female developmental stages or the development of female reproductive organs. Phthalate metabolites did not correlate with the physical characteristics and reproductive hormones in boys. Therefore, environmental exposure to phthalates, as determined by urinary phthalate metabolite levels of eight-year-old children, may affect reproductive hormone levels in children, indicating that further studies on the environmental health effects of phthalates are warranted.

Risk of death from cardiovascular disease associated with low-level arsenic exposure among long-term smokers in a US population-based study

International Nuclear Information System (INIS)

Farzan, Shohreh F.; Chen, Yu; Rees, Judy R.; Zens, M. Scot; Karagas, Margaret R.

2015-01-01

High levels of arsenic exposure have been associated with increases in cardiovascular disease risk. However, studies of arsenic's effects at lower exposure levels are limited and few prospective studies exist in the United States using long-term arsenic exposure biomarkers. We conducted a prospective analysis of the association between toenail arsenic and cardiovascular disease mortality using longitudinal data collected on 3939 participants in the New Hampshire Skin Cancer Study. Using Cox proportional hazard models adjusted for potential confounders, we estimated hazard ratios and 95% confidence intervals associated with the risk of death from any cardiovascular disease, ischemic heart disease, and stroke, in relation to natural-log transformed toenail arsenic concentrations. In this US population, although we observed no overall association, arsenic exposure measured from toenail clipping samples was related to an increased risk of ischemic heart disease mortality among long-term smokers (as reported at baseline), with increased hazard ratios among individuals with ≥ 31 total smoking years (HR: 1.52, 95% CI: 1.02, 2.27), ≥ 30 pack-years (HR: 1.66, 95% CI: 1.12, 2.45), and among current smokers (HR: 1.69, 95% CI: 1.04, 2.75). These results are consistent with evidence from more highly exposed populations suggesting a synergistic relationship between arsenic exposure and smoking on health outcomes and support a role for lower-level arsenic exposure in ischemic heart disease mortality. - Highlights: • Arsenic (As) has been associated with increased cardiovascular disease (CVD) risk. • Little is known about CVD effects at lower levels of As exposure common in the US. • Few have investigated the joint effects of As and smoking on CVD in US adults. • We examine chronic low-level As exposure and smoking in relation to CVD mortality. • Arsenic exposure may increase ischemic heart disease mortality among smokers in US

Risk of death from cardiovascular disease associated with low-level arsenic exposure among long-term smokers in a US population-based study

Energy Technology Data Exchange (ETDEWEB)

Farzan, Shohreh F. [Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH (United States); Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, NY (United States); Chen, Yu [Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, NY (United States); Rees, Judy R.; Zens, M. Scot [Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH (United States); Karagas, Margaret R., E-mail: margaret.r.karagas@dartmouth.edu [Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH (United States)

2015-09-01

High levels of arsenic exposure have been associated with increases in cardiovascular disease risk. However, studies of arsenic's effects at lower exposure levels are limited and few prospective studies exist in the United States using long-term arsenic exposure biomarkers. We conducted a prospective analysis of the association between toenail arsenic and cardiovascular disease mortality using longitudinal data collected on 3939 participants in the New Hampshire Skin Cancer Study. Using Cox proportional hazard models adjusted for potential confounders, we estimated hazard ratios and 95% confidence intervals associated with the risk of death from any cardiovascular disease, ischemic heart disease, and stroke, in relation to natural-log transformed toenail arsenic concentrations. In this US population, although we observed no overall association, arsenic exposure measured from toenail clipping samples was related to an increased risk of ischemic heart disease mortality among long-term smokers (as reported at baseline), with increased hazard ratios among individuals with ≥ 31 total smoking years (HR: 1.52, 95% CI: 1.02, 2.27), ≥ 30 pack-years (HR: 1.66, 95% CI: 1.12, 2.45), and among current smokers (HR: 1.69, 95% CI: 1.04, 2.75). These results are consistent with evidence from more highly exposed populations suggesting a synergistic relationship between arsenic exposure and smoking on health outcomes and support a role for lower-level arsenic exposure in ischemic heart disease mortality. - Highlights: • Arsenic (As) has been associated with increased cardiovascular disease (CVD) risk. • Little is known about CVD effects at lower levels of As exposure common in the US. • Few have investigated the joint effects of As and smoking on CVD in US adults. • We examine chronic low-level As exposure and smoking in relation to CVD mortality. • Arsenic exposure may increase ischemic heart disease mortality among smokers in US.

Arsenic and ultraviolet radiation exposure: melanoma in a New Mexico non-Hispanic white population.

Science.gov (United States)

Yager, Janice W; Erdei, Esther; Myers, Orrin; Siegel, Malcolm; Berwick, Marianne

2016-06-01

Cases of cutaneous melanoma and controls were enrolled in a New Mexico population-based study; subjects were administered questionnaires concerning ultraviolet (UV) and inorganic arsenic (iAs) exposure. Historical iAs exposure was estimated. UV exposure estimates were also derived using geospatial methods. Drinking water samples were collected for iAs analysis. Blood samples were collected for DNA repair (Comet) and DNA repair gene polymorphism assays. Arsenic concentrations were determined in urine and toenail samples. UV exposures during the previous 90 days did not vary significantly between cases and controls. Mean (±SD) current home iAs drinking water was not significantly different for cases and controls [3.98 μg/L (±3.67) vs. 3.47 μg/L (±2.40)]. iAs exposure showed no effect on DNA repair or association with melanoma. Results did not corroborate a previously reported association between toenail As and melanoma risk. Arsenic biomarkers in urine and toenail were highly significantly correlated with iAs in drinking water. A UV-DNA repair interaction for UV exposure over the previous 7-90 days was shown; cases had higher DNA damage than controls at low UV values. This novel finding suggests that melanoma cases may be more sensitive to low-level UV exposure than are controls. A UV-APEX1 interaction was shown. Subjects with the homozygous rare APEX1 DNA repair gene allele had a higher risk of early melanoma diagnosis at low UV exposure compared with those with the homozygous wild type or the heterozygote. Notably, a UV-arsenic interaction on inhibition of DNA repair was not observed at iAs drinking water concentrations below 10 ppb (μg/L).

Comparative proteomic analysis reveals heart toxicity induced by chronic arsenic exposure in rats

DEFF Research Database (Denmark)

Huang, Qingyu; Xi, Guochen; Alamdar, Ambreen

2017-01-01

Arsenic is a widespread metalloid in the environment, which poses a broad spectrum of adverse effects on human health. However, a global view of arsenic-induced heart toxicity is still lacking, and the underlying molecular mechanisms remain unclear. By performing a comparative quantitative...... proteomic analysis, the present study aims to investigate the alterations of proteome profile in rat heart after long-term exposure to arsenic. As a result, we found that the abundance of 81 proteins were significantly altered by arsenic treatment (35 up-regulated and 46 down-regulated). Among these, 33...... proteins were specifically associated with cardiovascular system development and function, including heart development, heart morphology, cardiac contraction and dilation, and other cardiovascular functions. It is further proposed that the aberrant regulation of 14 proteins induced by arsenic would disturb...

Non-melanoma skin cancer: occupational risk from UV light and arsenic exposure.

Science.gov (United States)

Surdu, Simona

2014-01-01

Non-melanoma skin cancer (NMSC) has a significant impact on public health and health care costs as a result of high morbidity and disfigurement due to the destruction of surrounding tissues. Although the mortality rates of these tumors are low, the high incidence rates determine a considerable number of deaths. NMSC is the most common type of skin cancer, representing about 1/3 of all malignancies diagnosed worldwide each year. The most common NMSC are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Studies on humans and experimental animals indicate that ultraviolet (UV) light and arsenic play important roles in the development of these skin malignancies. Several epidemiological studies have investigated the risk of developing NMSC and the potential link between exposure to sunlight and arsenic in the agricultural and industrial occupational settings. To date, the published literature suggests that there is no apparent skin cancer risk as regards workplace exposure to artificial UV light or arsenic. Concerning UV light from sun exposure at the workplace, most published studies indicated an elevated risk for SCC, but are less conclusive for BCC. Many of these studies are limited by the methodology used in the evaluation of occupational exposure and the lack of adjustment for major confounders. Therefore, further epidemiological studies are required to focus on exposure assessment at the individual level as well as potential interactions with other occupational and non-occupational exposures and individual susceptibility. In doing so, we can better quantify the true risk of skin cancer in exposed workers and inform effective public health prevention programs.

Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.; Bell, Matthew W.; Waalkes, Michael P.; Tokar, Erik J., E-mail: tokare@niehs.nih.gov

2015-07-01

Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomous growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells provide a

Epigenetic programming of obesity and diabetes by in utero exposure to gestational diabetes mellitus.

Science.gov (United States)

Ruchat, Stephanie-May; Hivert, Marie-France; Bouchard, Luigi

2013-10-01

It is now well accepted that offspring exposed to maternal undernutrition, obesity, or gestational diabetes mellitus have an increased risk for chronic diseases later in life, supporting the theory of the early origins of chronic diseases. However, the molecular mechanisms through which the exposure to an altered in utero environment translates into the development of chronic diseases are not yet well understood. Recently reported promising results help to resolve this issue. They suggest that epigenetic modifications are a potential mechanism for fetal metabolic programming. This review provides an overview of the relationship between the exposure to an altered intrauterine environment and fetal metabolic programming, focusing on gestational diabetes mellitus and epigenetic variations at adipokine candidate genes. © 2013 International Life Sciences Institute.

A longitudinal study of health effects of in utero radiation exposure from the Chernobyl accident

International Nuclear Information System (INIS)

Dardynskaya, I.; Hryhorczuk, D.; Anspaugh, L.R.; Khrouch, V.T.; Gavrilin, Y.I.; Shinkarev, S.M.; Dardynskiy, O.

2002-01-01

1500 children who were born between April 26, 1986, and December 31, 1987 (Study Groups 1 and 2) were identified from lists of children undergoing mandatory surveillance in the Minsk Chernobyl Dispensary. During pregnancy mothers of these children lived in highly contaminated territories in several areas of three Belarus Regions - Gomel, Mogilev, and Brest. Children in Study Group 1 were born between April 26, 1986, and January 31, 1987. The mothers of these children during their pregnancy period were exposed both to radiocesium and radioiodine. Children in Study Group 2 were born between February 1, 1987 and December 31, 1987. The mothers of children from Study Group 2 lived in the same areas as the mothers of children from Study Group 1, but during their pregnancy period were mainly exposed to radiocesium. The Control Group consists of children born between April 26, 1986, and December 31, 1987, to mothers living throughout pregnancy in the uncontaminated Vitebsk Region. These children were randomly selected from medical records of family-practice clinics, and were matched to Study Groups 1 and 2 by age and sex. To assess the health effects of in utero radiation exposure among the cohort, the specific protocol for annual health examination was developed in 1988. The study protocol included collection of data on family history; history of mothers pregnancy and delivery; head circumference at birth; annual measurements of standing height and weight; examination by neurologist; clinical thyroid evaluation, and ultrasound examination of the thyroid; annual measurements of levels of thyroid hormones and antibodies in children's blood (i.e. thyrotropin (TSH), total and free thyroxin (T4), triiodthyronin (T3), thyroglobulin (TG) and TG autoantibodies, thyroid binding globulin (TBG), and anti-TPO (thyroid microsomal )assay; annual blood count; analyses of the components of the immune system (T- cells, B-cells, immunoglobulins, complement, etc.); and data on general

Correlation of Breastmilk Arsenic With Maternal, Infant Urinary Arsenic and Drinking Water Arsenic in an Arsenic Affected Area of Bangladesh

Science.gov (United States)

Alauddin, M.; Islam, M. R.; Milton, A. H.; Alauddin, S. T.; Mouly, T.; Behri, E.; Ayesha, A.; Akter, S.; Islam, M. M.

2016-12-01

About 97% of population in Bangladesh depend on groundwater as the principle source of drinking water and this water is highly contaminated with inorganic arsenic. Consumption of arsenic contaminated drinking water by pregnant women raises the prospect of early life exposure to inorganic arsenic for newborn which may be lead to adverse health effect in later life. This work was carried out in parts of Gopalganj district in Bangladesh, a region affected by arsenic contamination in groundwater. The objective of the work was to assess potential early life exposure to arsenic for infants through breastfeeding by mothers who were drinking water with arsenic levels ranging from 100 to 300 µg/l. A cohort of 30 mother-baby pairs were selected for the current study. Breastmilk samples from mothers, urine samples from each pair of subjects at 1, 6 and 9 month age of infant were collected and total arsenic were determined in these samples. In addition speciation of urinary arsenic and metabolites were carried out in 12 mother-baby pairs. Median level for breastmilk arsenic were 0.50 µg/l. Urinary arsenic of infants did not correlate with breastmilk arsenic with progressing age of infants. Maternal and infant urinary total arsenic at 1 month age of infant showed some positive correlation (r = 0.39). In infant urine major metabolite were dimethyl arsenic acid (DMA) (approximately 70%) indicating good methylating capacity for infants at 1 and 6 months of age. In conclusion, infants were not exposed to arsenic through breastfeeding even though mothers were exposed to significant levels of arsenic through drinking water.

In utero cortisol and testosterone exposure and fear reactivity in infancy.

Science.gov (United States)

Bergman, Kristin; Glover, Vivette; Sarkar, Pampa; Abbott, Dave H; O'Connor, Thomas G

2010-03-01

Fetal programming is emerging as a major conceptual model for understanding developmental origins of health and disease, including behavioral outcomes. As part of a larger study of prenatal stress and child development, we examined the association between prenatal hormone exposure and fear reactivity, a temperament dimension that is a predictor of long-term behavioral adjustment. Amniotic fluid was collected from a sample of women undergoing clinically indicated amniocentesis for later analysis of cortisol and testosterone. Children with normal birth outcomes were recalled for follow-up assessment at 17 months, at which time we administered an observational assessment of temperament (lab-TAB; n=108). Information on pregnancy and obstetric outcome was included as covariates. Results indicated that there was a significant association between prenatal testosterone and observed fear reactivity in boys (r(53)=0.34, p=0.01); no significant effect was found in girls (r(54)=-0.07, ns); the effect remained when obstetric, psychosocial, and parental anxiety were controlled for. There was not a significant association between fetal cortisol exposure and fear reactivity. The prediction from in utero testosterone exposure to fear reactivity in boys extends prior research on prenatal testosterone and may represent an association with a general predisposition to greater arousal and reactivity. Copyright 2010 Elsevier Inc. All rights reserved.

[Studies on markers of exposure and early effect in areas with arsenic pollution: methods and results of the project SEpiAs. Epidemiological studies on population exposed to low-to-moderate arsenic concentration in drinking water].

Science.gov (United States)

Bustaffa, Elisa; Bianchi, Fabrizio

2014-01-01

Arsenic and its inorganic compounds are classified as human carcinogens. Several epidemiological studies conducted in areas of the world characterized by high arsenic concentration in drinking water, even up to 3,000 μg/l, report associations between arsenic exposure and skin, bladder, lung, liver and kidney cancer as well as cardiovascular diseases, diabetes and reproductive and developmental effects. Since general population is not exposed to these high arsenic concentrations in the last years attention focused on adverse health effects that low-to-moderate arsenic concentrations (0-150 μg/l) in drinking water could induce. The World Health Organization recommends a maximum limit of 10 μg/l for arsenic in drinking water. Almost all epidemiological studies conducted on populations exposed to low-to-moderate arsenic concentrations in drinking water are limited due to problems arising from both individual exposure assessment and low subjects number. The aim of the present review is to collect literature-based evidences regarding adverse health effects associated with exposure to low-to-moderate arsenic concentrations in drinking water (10-150 μg/l) in order to obtain a comprehensive picture of the health outcomes that such exposure can have on general population.

Lymphoma and lung cancer in offspring born to pregnant mice dosed with dibenzo[a,l]pyrene: The importance of in utero vs. lactational exposure

International Nuclear Information System (INIS)

Castro, David J.; Loehr, Christiane V.; Fischer, Kay A.; Pereira, Clifford B.; Williams, David E.

2008-01-01

The fetus and neonate cannot be viewed as 'little adults'; they are highly sensitive to toxicity from environmental chemicals. This phenomenon contributes to the fetal basis of adult disease. One example is transplacental carcinogenesis. Animal models demonstrate that environmental chemicals, to which pregnant women are daily exposed, can increase susceptibility of the offspring to cancer. It is uncertain to what degree in utero vs. lactational exposure contributes to cancer, especially for hydrophobic chemicals such as polyhalogenated biphenyls, ethers, dioxins, furans, etc., which can partition into breast milk. We developed a pregnant mouse model in which exposure to the polycyclic aromatic hydrocarbon (PAH), dibenzo[a,l]pyrene (DBP), during late gestation, produces an aggressive T-cell lymphoma in offspring between 3 and 6 months of age. Survivors exhibit multiple lung and liver (males) tumors. Here, we adopt a cross-foster design with litters born to dams treated with DBP exchanged with those born to dams treated with vehicle. Exposure to DBP in utero (about 2 days) produced significantly greater mortality than residual DBP exposure only through breast milk (3 weeks of lactation). As previously observed pups in all groups with an ahr b-1/d ('responsive') genotype were more susceptible to lymphoma mortality than ahr d/d ('non-responsive') siblings. At termination of the study at 10 months, mice exposed in utero also had greater lung tumor multiplicity than mice exposed only during lactation. Our results demonstrate that short exposure to DBP during late gestation presents a greater risk to offspring than exposure to this very hydrophobic PAH following 3 weeks of nursing

Arsenic exposure and outcomes of antimonial treatment in visceral leishmaniasis patients in Bihar, India: a retrospective cohort study.

Directory of Open Access Journals (Sweden)

Meghan R Perry

2015-03-01

Full Text Available In the late twentieth century, emergence of high rates of treatment failure with antimonial compounds (SSG for visceral leishmaniasis (VL caused a public health crisis in Bihar, India. We hypothesize that exposure to arsenic through drinking contaminated groundwater may be associated with SSG treatment failure due to the development of antimony-resistant parasites.A retrospective cohort design was employed, as antimony treatment is no longer in routine use. The study was performed on patients treated with SSG between 2006 and 2010. Outcomes of treatment were assessed through a field questionnaire and treatment failure used as a proxy for parasite resistance. Arsenic exposure was quantified through analysis of 5 water samples from within and surrounding the patient's home. A logistic regression model was used to evaluate the association between arsenic exposure and treatment failure. In a secondary analysis survival curves and Cox regression models were applied to assess the risk of mortality in VL patients exposed to arsenic.One hundred and ten VL patients treated with SSG were analysed. The failure rate with SSG was 59%. Patients with high mean local arsenic level had a non-statistically significant higher risk of treatment failure (OR = 1.78, 95% CI: 0.7-4.6, p = 0.23 than patients using wells with arsenic concentration <10 μg/L. Twenty one patients died in our cohort, 16 directly as a result of VL. Arsenic levels ≥ 10 μg/L increased the risk of all-cause (HR 3.27; 95% CI: 1.4-8.1 and VL related (HR 2.65; 95% CI: 0.96-7.65 deaths. This was time dependent: 3 months post VL symptom development, elevated risks of all-cause mortality (HR 8.56; 95% CI: 2.5-29.1 and of VL related mortality (HR 9.27; 95% CI: 1.8-49.0 were detected.This study indicates a trend towards increased treatment failure in arsenic exposed patients. The limitations of the retrospective study design may have masked a strong association between arsenic exposure and selection

Consequences of the Chernobyl accident in Russia: search for effects of radiation exposure in utero using psychometric tests

International Nuclear Information System (INIS)

Ryabukhin, Yu.S.; Ryabukhin, V.Yu.

2001-01-01

Psychometric indicators for mental development of children in towns distinguished by radioactive contamination resulting from the Chernobyl accident are studied. Using some radiological information obtained after the Chernobyl accident, values of expected intelligence quotient (IQ) reduction have been assessed as a result of brain exposure in utero due to various components of dose. Comparing the results of examinations in Novozybkov, Klintsy and Obninsk, no confident evidence has been obtained that radiation exposure of the developing brain exerts influence on indicators for mental development [ru

Health burden of skin lesions at low arsenic exposure through groundwater in Pakistan. Is river the source?

International Nuclear Information System (INIS)

Fatmi, Zafar; Azam, Iqbal; Ahmed, Faiza; Kazi, Ambreen; Gill, Albert Bruce; Kadir, Muhmmad Masood; Ahmed, Mubashir; Ara, Naseem; Janjua, Naveed Zafar

2009-01-01

A significant proportion of groundwater in south Asia is contaminated with arsenic. Pakistan has low levels of arsenic in groundwater compared with China, Bangladesh and India. A representative multi-stage cluster survey conducted among 3874 persons ≥15 years of age to determine the prevalence of arsenic skin lesions, its relation with arsenic levels and cumulative arsenic dose in drinking water in a rural district (population: 1.82 million) in Pakistan. Spot-urine arsenic levels were compared among individuals with and without arsenic skin lesions. In addition, the relation of age, body mass index, smoking status with arsenic skin lesions was determined. The geographical distribution of the skin lesions and arsenic-contaminated wells in the district were ascertained using global positioning system. The total arsenic, inorganic and organic forms, in water and spot-urine samples were determined by atomic absorption spectrophotometry. The prevalence of skin lesions of arsenic was estimated for complex survey design, using surveyfreq and surveylogistic options of SAS 9.1 software.The prevalence of definitive cases i.e. hyperkeratosis of both palms and soles, was 3.4 per 1000 and suspected cases i.e. any sign of arsenic skin lesions (melanosis and/or keratosis), were 13.0 per 1000 among ≥15-year-old persons in the district. Cumulative arsenic exposure (dose) was calculated from levels of arsenic in water and duration of use of current drinking water source. Prevalence of skin lesions increases with cumulative arsenic exposure (dose) in drinking water and arsenic levels in urine. Skin lesions were 2.5-fold among individuals with BMI 2 . Geographically, more arsenic-contaminated wells and skin lesions were alongside Indus River, suggests a strong link between arsenic contamination of groundwater with proximity to river.This is the first reported epidemiological and clinical evidence of arsenic skin lesions due to groundwater in Pakistan. Further investigations and

Health burden of skin lesions at low arsenic exposure through groundwater in Pakistan. Is river the source?

Energy Technology Data Exchange (ETDEWEB)

Fatmi, Zafar, E-mail: zafar.fatmi@aku.edu [Department of Community Health Sciences, Aga Khan University, Stadium Road, P.O. Box 3500, Karachi (Pakistan); Azam, Iqbal; Ahmed, Faiza; Kazi, Ambreen; Gill, Albert Bruce; Kadir, Muhmmad Masood; Ahmed, Mubashir; Ara, Naseem; Janjua, Naveed Zafar [Department of Community Health Sciences, Aga Khan University, Stadium Road, P.O. Box 3500, Karachi (Pakistan)

2009-07-15

A significant proportion of groundwater in south Asia is contaminated with arsenic. Pakistan has low levels of arsenic in groundwater compared with China, Bangladesh and India. A representative multi-stage cluster survey conducted among 3874 persons {>=}15 years of age to determine the prevalence of arsenic skin lesions, its relation with arsenic levels and cumulative arsenic dose in drinking water in a rural district (population: 1.82 million) in Pakistan. Spot-urine arsenic levels were compared among individuals with and without arsenic skin lesions. In addition, the relation of age, body mass index, smoking status with arsenic skin lesions was determined. The geographical distribution of the skin lesions and arsenic-contaminated wells in the district were ascertained using global positioning system. The total arsenic, inorganic and organic forms, in water and spot-urine samples were determined by atomic absorption spectrophotometry. The prevalence of skin lesions of arsenic was estimated for complex survey design, using surveyfreq and surveylogistic options of SAS 9.1 software.The prevalence of definitive cases i.e. hyperkeratosis of both palms and soles, was 3.4 per 1000 and suspected cases i.e. any sign of arsenic skin lesions (melanosis and/or keratosis), were 13.0 per 1000 among {>=}15-year-old persons in the district. Cumulative arsenic exposure (dose) was calculated from levels of arsenic in water and duration of use of current drinking water source. Prevalence of skin lesions increases with cumulative arsenic exposure (dose) in drinking water and arsenic levels in urine. Skin lesions were 2.5-fold among individuals with BMI <18.5 kg/m{sup 2}. Geographically, more arsenic-contaminated wells and skin lesions were alongside Indus River, suggests a strong link between arsenic contamination of groundwater with proximity to river.This is the first reported epidemiological and clinical evidence of arsenic skin lesions due to groundwater in Pakistan. Further

Health burden of skin lesions at low arsenic exposure through groundwater in Pakistan. Is river the source?

Science.gov (United States)

Fatmi, Zafar; Azam, Iqbal; Ahmed, Faiza; Kazi, Ambreen; Gill, Albert Bruce; Kadir, Muhmmad Masood; Ahmed, Mubashir; Ara, Naseem; Janjua, Naveed Zafar

2009-07-01

A significant proportion of groundwater in south Asia is contaminated with arsenic. Pakistan has low levels of arsenic in groundwater compared with China, Bangladesh and India. A representative multi-stage cluster survey conducted among 3874 persons > or = 15 years of age to determine the prevalence of arsenic skin lesions, its relation with arsenic levels and cumulative arsenic dose in drinking water in a rural district (population: 1.82 million) in Pakistan. Spot-urine arsenic levels were compared among individuals with and without arsenic skin lesions. In addition, the relation of age, body mass index, smoking status with arsenic skin lesions was determined. The geographical distribution of the skin lesions and arsenic-contaminated wells in the district were ascertained using global positioning system. The total arsenic, inorganic and organic forms, in water and spot-urine samples were determined by atomic absorption spectrophotometry. The prevalence of skin lesions of arsenic was estimated for complex survey design, using surveyfreq and surveylogistic options of SAS 9.1 software.The prevalence of definitive cases i.e. hyperkeratosis of both palms and soles, was 3.4 per 1000 and suspected cases i.e. any sign of arsenic skin lesions (melanosis and/or keratosis), were 13.0 per 1000 among > or = 15-year-old persons in the district. Cumulative arsenic exposure (dose) was calculated from levels of arsenic in water and duration of use of current drinking water source. Prevalence of skin lesions increases with cumulative arsenic exposure (dose) in drinking water and arsenic levels in urine. Skin lesions were 2.5-fold among individuals with BMI <18.5 kg/m2. Geographically, more arsenic-contaminated wells and skin lesions were alongside Indus River, suggests a strong link between arsenic contamination of groundwater with proximity to river.This is the first reported epidemiological and clinical evidence of arsenic skin lesions due to groundwater in Pakistan. Further

Arsenic (+3 oxidation state) methyltransferase and the inorganic arsenic methylation phenotype

International Nuclear Information System (INIS)

Li Jiaxin; Waters, Stephen B.; Drobna, Zuzana; Devesa, Vicenta; Styblo, Miroslav; Thomas, David J.

2005-01-01

Inorganic arsenic is enzymatically methylated; hence, its ingestion results in exposure to the parent compound and various methylated arsenicals. Both experimental and epidemiological evidences suggest that some of the adverse health effects associated with chronic exposure to inorganic arsenic may be mediated by these methylated metabolites. If i As methylation is an activation process, then the phenotype for inorganic arsenic methylation may determine risk associated with exposure to this metalloid. We examined inorganic arsenic methylation phenotypes and arsenic (+3 oxidation state) methyltransferase genotypes in four species: three that methylate inorganic arsenic (human (Homo sapiens), rat (Rattus norwegicus), and mouse (Mus musculus)) and one that does not methylate inorganic arsenic (chimpanzee, Pan troglodytes). The predicted protein products from arsenic (+3 oxidation state) methyltransferase are similar in size for rat (369 amino acid residues), mouse (376 residues), and human (375 residues). By comparison, a 275-nucleotide deletion beginning at nucleotide 612 in the chimpanzee gene sequence causes a frameshift that leads to a nonsense mutation for a premature stop codon after amino acid 205. The null phenotype for inorganic arsenic methylation in the chimpanzee is likely due to the deletion in the gene for arsenic (+3 oxidation state) methyltransferase that yields an inactive truncated protein. This lineage-specific loss of function caused by the deletion event must have occurred in the Pan lineage after Homo-Pan divergence about 5 million years ago

The PHACS SMARTT Study: Assessment of the Safety of In Utero Exposure to Antiretroviral Drugs

Directory of Open Access Journals (Sweden)

Russell Barrett Van Dyke

2016-05-01

Full Text Available The Surveillance Monitoring for ART Toxicities (SMARTT cohort of the Pediatric HIV/AIDS Cohort Study (PHACS includes over 3500 HIV-exposed but uninfected (HEU infants and children at 22 sites in the U.S. including Puerto Rico. The goal of the study is to determine the safety of in utero exposure to antiretrovirals (ARV and to estimate the incidence of adverse events. Domains being assessed include metabolic, growth and development, cardiac, neurological, neurodevelopmental, behavior, language, and hearing. SMARTT employs an innovative trigger-based design as an efficient means to identify and evaluate adverse events. Participants who met a predefined clinical or laboratory threshold (trigger undergo additional evaluations to define their case status. After adjusting for birth cohort and other factors, there was no significant increase in the likelihood of meeting overall case status (case in any domain with exposure to combination ARVs (cARV, any ARV class, or any specific ARV. However, several individual ARVs were significantly associated with case status in individual domains, including zidovudine for a metabolic case, first trimester stavudine for a language case, and didanosine plus stavudine for a neurodevelopmental case. We found an increased rate of preterm birth with first trimester exposure to protease inhibitor-based cARV. Although there was no overall increase in congenital anomalies with first trimester cARV, a significant increase was seen with exposure to atazanavir, ritonavir, and didanosine plus stavudine. Tenofovir exposure was associated with significantly lower mean whole-body bone mineral content in the newborn period and a lower length and head circumference at 1 year of age. With neurodevelopmental testing at 1 year of age, specific ARVs (atazanavir, ritonavir-boosted lopinavir, nelfinavir, and tenofovir were associated with lower performance, although all groups were within the normal range. No ARVs or classes were

Cortex and hippocampus DNA epigenetic response to a long-term arsenic exposure via drinking water.

Science.gov (United States)

Du, Xiaoyan; Tian, Meiping; Wang, Xiaoxue; Zhang, Jie; Huang, Qingyu; Liu, Liangpo; Shen, Heqing

2018-03-01

The neurotoxicity of arsenic is a serious health problem, especially for children. DNA epigenetic change may be an important pathogenic mechanism, but the molecular pathway remains obscure. In this study, the weaned male Sprague-Dawly (SD) rats were treated with arsenic trioxide via drinking water for 6 months, simulating real developmental exposure situation of children. Arsenic exposure impaired the cognitive abilities, and altered the expression of neuronal activity-regulated genes. Total arsenic concentrations of cortex and hippocampus tissues were significantly increased in a dose-dependent manner. The reduction in 5-methylcytosine (5 mC) and 5-hydroxymethylcytosine (5hmC) levels as well as the down-regulation of DNA methyltransferases (DNMTs) and ten-eleven translocations (TETs) expression suggested that DNA methylation/demethylation processes were significantly suppressed in brain tissues. S-adenosylmethionine (SAM) level wasn't changed, but the expression of the important indicators of oxidative/anti-oxidative balance and tricarboxylic acid (TCA) cycle was significantly deregulated. Overall, arsenic can disrupt oxidative/anti-oxidative balance, further inhibit TETs expression through TCA cycle and alpha-ketoglutarate (α-KG) pathway, and consequently cause DNA methylation/demethylation disruption. The present study implies oxidative stress but not SAM depletion may lead to DNA epigenetic alteration and arsenic neurotoxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Use of human metabolic studies and urinary arsenic speciation is assessing arsenic exposure

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Johnson, L.R.; Farmer, J.G. (Memphis State Univ., TN (United States) Univ. of Edinburgh (United Kingdom))

1991-01-01

The use of hair and nail analyses to assess human exposure to the trace metalloid arsenic (As) is hindered by the possibility of external contamination. Even though urine represents the major excretory route, its use as an indicator of exposure is limited when no distinction is made between the nontoxic organoarsenical (arsenobetaine) excreted following the consumption of seafood and the toxic inorganic forms of As and related metabolites. The development of analytical techniques capable of separating the different chemical species of As in urine have shown that the ingestion of inorganic As (AsV or AsIII) by animals and man triggers an in vivo reduction/methylation process resulting in excretion of the less toxic species, monomethylarsonic acid (MMAA) and dimethylarsinic acid (DMAA). This paper establishes the uptake, bio-transformation and elimination patterns reflected in urinary As following carefully controlled experimental exposure.

Arsenic levels in wipe samples collected from play structures constructed with CCA-treated wood: Impact on exposure estimates

Energy Technology Data Exchange (ETDEWEB)

Barraj, Leila M. [Chemical Regulation and Food Safety, Exponent, Inc., Suite 1100, 1150 Connecticut Ave., NW, Washington, DC 20036 (United States)], E-mail: lbarraj@exponent.com; Scrafford, Carolyn G. [Chemical Regulation and Food Safety, Exponent, Inc., Suite 1100, 1150 Connecticut Ave., NW, Washington, DC 20036 (United States); Eaton, W. Cary [RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709 (United States); Rogers, Robert E.; Jeng, Chwen-Jyh [Toxcon Health Sciences Research Centre Inc., 9607 - 41 Avenue, Edmonton, Alberta, T6E 5X7 (Canada)

2009-04-01

Lumber treated with chromated copper arsenate (CCA) has been used in residential outdoor wood structures and playgrounds. The U.S. EPA has conducted a probabilistic assessment of children's exposure to arsenic from CCA-treated structures using the Stochastic Human Exposure and Dose Simulation model for the wood preservative scenario (SHEDS-Wood). The EPA assessment relied on data from an experimental study using adult volunteers and designed to measure arsenic in maximum hand and wipe loadings. Analyses using arsenic handloading data from a study of children playing on CCA-treated play structures in Edmonton, Canada, indicate that the maximum handloading values significantly overestimate the exposure that occurs during actual play. The objective of our paper is to assess whether the dislodgeable arsenic residues from structures in the Edmonton study are comparable to those observed in other studies and whether they support the conclusion that the values derived by EPA using modeled maximum loading values overestimate hand exposures. We compared dislodgeable arsenic residue data from structures in the playgrounds in the Edmonton study to levels observed in studies used in EPA's assessment. Our analysis showed that the dislodgeable arsenic levels in the Edmonton playground structures are similar to those in the studies used by EPA. Hence, the exposure estimates derived using the handloading data from children playing on CCA-treated structures are more representative of children's actual exposures than the overestimates derived by EPA using modeled maximum values. Handloading data from children playing on CCA-treated structures should be used to reduce the uncertainty of modeled estimates derived using the SHEDS-Wood model.

Estimating Inorganic Arsenic Exposure from U.S. Rice and Total Water Intakes.

Science.gov (United States)

Mantha, Madhavi; Yeary, Edward; Trent, John; Creed, Patricia A; Kubachka, Kevin; Hanley, Traci; Shockey, Nohora; Heitkemper, Douglas; Caruso, Joseph; Xue, Jianping; Rice, Glenn; Wymer, Larry; Creed, John T

2017-05-30

Among nonoccupationally exposed U.S. residents, drinking water and diet are considered primary exposure pathways for inorganic arsenic (iAs). In drinking water, iAs is the primary form of arsenic (As), while dietary As speciation techniques are used to differentiate iAs from less toxic arsenicals in food matrices. Our goal was to estimate the distribution of iAs exposure rates from drinking water intakes and rice consumption in the U.S. population and ethnic- and age-based subpopulations. The distribution of iAs in drinking water was estimated by population, weighting the iAs concentrations for each drinking water utility in the Second Six-Year Review data set. To estimate the distribution of iAs concentrations in rice ingested by U.S. consumers, 54 grain-specific, production-weighted composites of rice obtained from U.S. mills were extracted and speciated using both a quantitative dilute nitric acid extraction and speciation (DNAS) and an in vitro gastrointestinal assay to provide an upper bound and bioaccessible estimates, respectively. Daily drinking water intake and rice consumption rate distributions were developed using data from the What We Eat in America (WWEIA) study. Using these data sets, the Stochastic Human Exposure and Dose Simulation (SHEDS) model estimated mean iAs exposures from drinking water and rice were 4.2 μg/day and 1.4 μg/day, respectively, for the entire U.S. population. The Tribal, Asian, and Pacific population exhibited the highest mean daily exposure of iAs from cooked rice (2.8 μg/day); the mean exposure rate for children between ages 1 and 2 years in this population is 0.104 μg/kg body weight (BW)/day. An average consumer drinking 1.5 L of water daily that contains between 2 and 3 ng iAs/mL is exposed to approximately the same amount of iAs as a mean Tribal, Asian, and Pacific consumer is exposed to from rice. https://doi.org/10.1289/EHP418. Among nonoccupationally exposed U.S. residents, drinking water and diet are considered

Association of cadmium and arsenic exposure with salivary telomere length in adolescents in Terai, Nepal

Energy Technology Data Exchange (ETDEWEB)

Fillman, Toki, E-mail: tokif@humeco.m.u-tokyo.ac.jp [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-0033 (Japan); Shimizu-Furusawa, Hana, E-mail: hana-shimizu@umin.ac.jp [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-0033 (Japan); Ng, Chris Fook Sheng, E-mail: chrisng-tky@umin.ac.jp [Department of Pediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki (Japan); Parajuli, Rajendra Prasad, E-mail: rp.parajuli@mcgill.ca [Basu Laboratory, CINE Building, Macdonald Campus, Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Quebec (Canada); Watanabe, Chiho, E-mail: chiho@humeco.m.u-tokyo.ac.jp [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-0033 (Japan)

2016-08-15

Background: Cadmium and arsenic are ubiquitous metals commonly found in the environment which can harm human health. A growing body of research shows telomere length as a potential biomarker of future disease risk. Few studies have examined the effects of metals on telomere length and none have focused on adolescents. Objectives: In this study, the impact of cadmium and arsenic on salivary telomere length was studied in adolescents in Terai, Nepal. Methods: Adolescents aged 12–16 years old (n=351)were recruited where questionnaire interviews and both saliva and urine collection took place. Telomere length was determined by quantitative polymerase chain reaction using DNA extracted from saliva. Urinary cadmium and arsenic concentration were measured by inductively coupled plasma mass spectrometry. Multivariable linear regression was used to examine associations between urinary metals and salivary telomere length. Results: The geometric means and standard deviations of cadmium and arsenic were 0.33±0.33 μg/g creatinine and 196.0±301.1 μg/g creatinine, respectively. Urinary cadmium concentration was negatively associated with salivary telomere length after adjustment for confounders (β=−0.24, 95% CI −0.42,−0.07). Arsenic showed positive associations with telomere length but did not reach statistical significance. Conclusions: This is the first study to demonstrate that cadmium may shorten adolescent telomeres, even at exposure levels that may be considered low. These results agree with prior experimental and adult epidemiological studies, and also help identify the mechanism of DNA damage by cadmium. This study expanded current evidence on the harmful effects of cadmium exposure on telomere length even to adolescents. - Highlights: • This is the first study examining metal exposure on telomere length in adolescents. • Urinary cadmium levels were similar to non-industrially polluted levels in Asia. • Urinary arsenic levels were as high as groundwater

Association of cadmium and arsenic exposure with salivary telomere length in adolescents in Terai, Nepal

International Nuclear Information System (INIS)

Fillman, Toki; Shimizu-Furusawa, Hana; Ng, Chris Fook Sheng; Parajuli, Rajendra Prasad; Watanabe, Chiho

2016-01-01

Background: Cadmium and arsenic are ubiquitous metals commonly found in the environment which can harm human health. A growing body of research shows telomere length as a potential biomarker of future disease risk. Few studies have examined the effects of metals on telomere length and none have focused on adolescents. Objectives: In this study, the impact of cadmium and arsenic on salivary telomere length was studied in adolescents in Terai, Nepal. Methods: Adolescents aged 12–16 years old (n=351)were recruited where questionnaire interviews and both saliva and urine collection took place. Telomere length was determined by quantitative polymerase chain reaction using DNA extracted from saliva. Urinary cadmium and arsenic concentration were measured by inductively coupled plasma mass spectrometry. Multivariable linear regression was used to examine associations between urinary metals and salivary telomere length. Results: The geometric means and standard deviations of cadmium and arsenic were 0.33±0.33 μg/g creatinine and 196.0±301.1 μg/g creatinine, respectively. Urinary cadmium concentration was negatively associated with salivary telomere length after adjustment for confounders (β=−0.24, 95% CI −0.42,−0.07). Arsenic showed positive associations with telomere length but did not reach statistical significance. Conclusions: This is the first study to demonstrate that cadmium may shorten adolescent telomeres, even at exposure levels that may be considered low. These results agree with prior experimental and adult epidemiological studies, and also help identify the mechanism of DNA damage by cadmium. This study expanded current evidence on the harmful effects of cadmium exposure on telomere length even to adolescents. - Highlights: • This is the first study examining metal exposure on telomere length in adolescents. • Urinary cadmium levels were similar to non-industrially polluted levels in Asia. • Urinary arsenic levels were as high as groundwater

Occupational exposure to chromium, copper and arsenic during work with impregnated wood in joinery shops.

Science.gov (United States)

Nygren, O; Nilsson, C A; Lindahl, R

1992-10-01

CCA-impregnated timber contains copper, chromium and arsenic (CCA), and occupational exposure to wood dust as well as the CCA compounds may occur in work with such timber. Dust from commercially available impregnated wood has been found to contain hexavalent chromium, which is regarded as a carcinogen. Apart from determinations of the total amounts of the CCA compounds, specific determination of hexavalent chromium is therefore essential. Selective methods have been applied for control of the work environment in six joinery shops. The mean exposure to wood dust was found to be below 1 mg m-3. The mean airborne concentration of arsenic around various types of joinery machines was in the range from 0.54 to 3.1 micrograms m-3. No hexavalent chromium was detected in any samples and no increased concentrations of arsenic were found in urine from the workers. The presence of arsenic in the work-room air must be considered for appropriate assessment of the occupational environment in joinery shops.

Vinclozolin Exposure in Utero Induces Postpubertal Prostatitis and Reduces Sperm Production via a Reversible Hormone-Regulated Mechanism

OpenAIRE

Cowin, Prue A.; Gold, Elspeth; Aleksova, Jasna; O'Bryan, Moira K.; Foster, Paul M. D.; Scott, Hamish S.; Risbridger, Gail P.

2010-01-01

Vinclozolin is an endocrine-disrupting chemical (EDC) that binds with high affinity to the androgen receptor (AR) and blocks the action of gonadal hormones on male reproductive organs. An alternative mechanism of action of Vinclozolin involves transgenerational effects on the male reproductive tract. We previously reported in utero Vinclozolin exposure-induced prostatitis (prostate inflammation) in postpubertal rats concurrent with down-regulation of AR and increased nuclear factor-κB activat...

Transplacental and early life exposure to inorganic arsenic affected development and behavior in offspring rats

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Xi, Shuhua; Jin, Yaping; Sun, Guifan [China Medical University, Department of Environmental and Occupational Health, College of Public Health, Shenyang, Liaoning (China); Sun, Wenjuan; Wang, Fengzhi [Shenyang Medical College, Department of Preventive Medicine, Shenyang, Liaoning (China)

2009-06-15

To evaluate the developmental neurotoxicity of arsenic in offspring rats by transplacental and early life exposure to sodium arsenite in drinking water, the pregnant rats or lactating dams, and weaned pups were given free access to drinking water, which contained arsenic at concentrations of 0, 10, 50, 100 mg/L from GD 6 until PND 42. A battery of physical and behavioral tests was applied to evaluate the functional outcome of pups. Pups in arsenic exposed groups weighed less than controls throughout lactation and weaning. Body weight of 10, 50 and 100 mg/L arsenic exposed groups decreased significantly on PND 42, 16 and 12, respectively. Physical development (pinna unfolding, fur appearance, incisor eruption, or eye opening) in pups displayed no significant differences between control and arsenic treated groups. The number of incidences within the 100 mg/L arsenic treated group, in tail hung, auditory startle and visual placing showed significant decrease compared to the control group (p<0.05). In square water maze test, the trained numbers to finish the trials successfully in 50 and 100 mg/L arsenic exposed groups increased remarkably compared to control group, and there was a dose-related increase (p<0.01) observed. Taken together, these data show that exposure of inorganic arsenite to pregnant dams and offspring pups at levels up to 100 mg/L in drinking water may affect their learning and memory functions and neuromotor reflex. (orig.)

Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression

Directory of Open Access Journals (Sweden)

Chia-Yu Chang

2015-01-01

Full Text Available Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM and open field test (OFT in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST and forced swimming test (FST in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.

Chronic arsenic poisoning from burning high-arsenic-containing coal in Guizhou, China

Energy Technology Data Exchange (ETDEWEB)

Liu, J.; Zheng, B.S.; Aposhian, H.V.; Zhou, Y.S.; Chen, M.L.; Zhang, A.H.; Waalkes, M.P. [NIEHS, Research Triangle Park, NC (USA)

2002-07-01

Arsenic is an environmental hazard and the reduction of drinking water arsenic levels is under consideration. People are exposed to arsenic not only through drinking water but also through arsenic-contaminated air and food. Here the health effects of arsenic exposure from burning high arsenic-containing coal in Guizhou, China was investigated. Coal is burned inside the home in open pits for daily cooking and crop drying, producing a high concentration of arsenic in indoor air. Arsenic in the air coats and permeates food being dried producing high concentrations in food; however, arsenic concentrations in the drinking water are in the normal range. The estimated sources of total arsenic exposure in this area are from arsenic-contaminated food (50-80%), air (10-20%), water (1-5%), and direct contact in coal-mining workers (1%). At least 3,000 patients with arsenic poisoning were found in the Southwest Prefecture of Guizhou, and approximately 200,000 people are at risk for such over exposures. Skin lesions are common, including keratosis of the hands and feet, pigmentation on the trunk, skin ulceration, and skin cancers. Toxicities to internal organs, including lung dysfunction, neuropathy, and nephrotoxicity, are clinically evident. The prevalence of hepatomegaly was 20%, and cirrhosis, ascites, and liver cancer are the most serious outcomes of arsenic poisoning. The Chinese government and international organizations are attempting to improve the house conditions and the coal source, and thereby protect human health in this area.

Arsenic pollution sources.

Science.gov (United States)

Garelick, Hemda; Jones, Huw; Dybowska, Agnieszka; Valsami-Jones, Eugenia

2008-01-01

Arsenic is a widely dispersed element in the Earth's crust and exists at an average concentration of approximately 5 mg/kg. There are many possible routes of human exposure to arsenic from both natural and anthropogenic sources. Arsenic occurs as a constituent in more than 200 minerals, although it primarily exists as arsenopyrite and as a constituent in several other sulfide minerals. The introduction of arsenic into drinking water can occur as a result of its natural geological presence in local bedrock. Arsenic-containing bedrock formations of this sort are known in Bangladesh, West Bengal (India), and regions of China, and many cases of endemic contamination by arsenic with serious consequences to human health are known from these areas. Significant natural contamination of surface waters and soil can arise when arsenic-rich geothermal fluids come into contact with surface waters. When humans are implicated in causing or exacerbating arsenic pollution, the cause can almost always be traced to mining or mining-related activities. Arsenic exists in many oxidation states, with arsenic (III) and (V) being the most common forms. Similar to many metalloids, the prevalence of particular species of arsenic depends greatly on the pH and redox conditions of the matrix in which it exists. Speciation is also important in determining the toxicity of arsenic. Arsenic minerals exist in the environment principally as sulfides, oxides, and phosphates. In igneous rocks, only those of volcanic origin are implicated in high aqueous arsenic concentrations. Sedimentary rocks tend not to bear high arsenic loads, and common matrices such as sands and sandstones contain lower concentrations owing to the dominance of quartz and feldspars. Groundwater contamination by arsenic arises from sources of arsenopyrite, base metal sulfides, realgar and orpiment, arsenic-rich pyrite, and iron oxyhydroxide. Mechanisms by which arsenic is released from minerals are varied and are accounted for by

Effects of in utero and lactational exposure to triphenyltin chloride on pregnancy outcome and postnatal development in rat offspring.

Science.gov (United States)

Grote, Konstanze; Hobler, Carolin; Andrade, Anderson J M; Grande, Simone Wichert; Gericke, Christine; Talsness, Chris E; Appel, Klaus E; Chahoud, Ibrahim

2007-09-05

The organotin compound (OTC) triphenyltin (TPT) is used extensively as a herbicide, pesticide and fungicide in agriculture as well as, together with tributyltin (TBT), in marine antifouling paints. We studied the effects of in utero exposure to 2 or 6 mg triphenyltinchloride (TPTCl)/kgb.w. on pregnancy outcome and postnatal development in rat offspring. Gravid Wistar rats were treated per gavage from gestational day 6 until the end of lactation. In the 6 mg TPTCl dose group gestational mortality in dams as well as an increased incidence of anticipated and delayed parturition was observed. Furthermore, treatment resulted in a significant increase in perinatal mortality, a decrease in lactational body weight gain as well as in delayed physical maturation of offspring. Similarily, exposure to 2mg TPTCl/kgb.w. resulted in a significant increase in perinatal mortality and in delayed eye opening. Lactational body weight gain and other landmarks of physical maturation were unaffected in the low dose group. We conclude, that in utero exposure to TPTCl at the described dose levels severely affected pregnancy outcome and perinatal survival of offspring. These results were unexpected, as in two earlier studies with pubertal rats TPTCl at the same dose levels no signs of general toxicity were observed.

In utero exposure to female hormones and germ cell tumors in children.

Science.gov (United States)

Shankar, Sadhna; Davies, Stella; Giller, Roger; Krailo, Mark; Davis, Mary; Gardner, Kathleen; Cai, Hui; Robison, Leslie; Shu, Xiao-Ou

2006-03-01

Maternal exposure to exogenous female hormones during pregnancy has been implicated as a risk factor for malignant germ cell tumors (GCTs) in the offspring in some epidemiologic studies of testicular and ovarian carcinoma in adults. From 1996 to 2002, 278 children younger than 15 years of age with malignant GCTs and 423 healthy controls, frequency-matched for geographic location, age, and sex were enrolled in a case-control study to investigate whether in utero exposure to female hormones is associated with the risk of malignant GCT in children. Cases were recruited from 84 institutions in the U.S. and controls were enrolled through random digit dialing. Information was obtained through telephone interview with the biological mothers of the subjects and through blinded review of the mothers' medical records. Neither self-reported (odds ratio [OR] = 1.15; 95% confidence interval [CI], 0.63, 2.12) nor medical chart based (OR = 1.14; 95% CI, 0.75, 1.73) maternal exposure to exogenous female hormones was related to malignant GCT risk. Pregnancy-related conditions that may have altered serum levels of circulating female hormones were also unrelated to the risk of GCT in the offspring. This study failed to provide strong evidence to support the hypothesis that maternal exposure to exogenous female hormones during pregnancy increases the risk of GCT in the offspring.

Postnatal arsenic exposure and attention impairment in school children.

Science.gov (United States)

Rodríguez-Barranco, Miguel; Gil, Fernando; Hernández, Antonio F; Alguacil, Juan; Lorca, Andres; Mendoza, Ramón; Gómez, Inmaculada; Molina-Villalba, Isabel; González-Alzaga, Beatriz; Aguilar-Garduño, Clemente; Rohlman, Diane S; Lacasaña, Marina

2016-01-01

Over the last few decades there has been an increased concern about the health risks from exposure to metallic trace elements, including arsenic, because of their potential neurotoxic effects on the developing brain. This study assessed whether urinary arsenic (UA) levels are associated with attention performance and Attention-Deficit/Hyperactivity Disorder (ADHD) in children living in an area with high industrial and mining activities in Southwestern Spain. A cross-sectional study was conducted on 261 children aged 6-9 years. Arsenic levels were determined in urine samples. Attention was measured by using 4 independent tools: a) tests from the Behavioral Assessment and Research System (BARS) designed to measure attention function: Simple Reaction Time Test (RTT), Continuous Performance Test (CPT) and Selective Attention Test (SAT); b) AULA Test, a virtual reality (VR)-based test that evaluates children's response to several stimuli in an environment simulating a classroom; c) Child Behavior Checklist (CBCL), administered to parents; and d) Teacher's Report Form (TRF), administered to teachers. Multivariate linear and logistic regression models, adjusted for potential confounders, were used to estimate the magnitude of the association between UA levels and attention performance scores. Higher UA levels were associated with an increased latency of response in RTT (β = 12.3; 95% confidence interval (CI): 3.5-21.1) and SAT (β = 3.6; 95% CI: .4-6.8) as well as with worse performance on selective and focalized attention in the AULA test (β for impulsivity = .6; 95% CI: .1-1.1; β for inattention = .5; 95% CI: .03-1.0). A dose-response relationship was observed between UA levels and inattention and impulsivity scores. In contrast, results from the CBCL and TRF tests failed to show a significant association with UA levels. In conclusion, UA levels were associated with impaired attention/cognitive function, even at levels considered safe. These results provide

Arsenic exposure induces the Warburg effect in cultured human cells

Energy Technology Data Exchange (ETDEWEB)

Zhao, Fei; Severson, Paul; Pacheco, Samantha; Futscher, Bernard W.; Klimecki, Walter T., E-mail: klimecki@pharmacy.arizona.edu

2013-08-15

Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure to arsenite (75 ppb) is sufficient to induce aerobic glycolysis (the Warburg effect) as a generalized phenomenon in cultured human primary cells and cell lines. Expanded studies in one such cell line, the non-malignant pulmonary epithelial line, BEAS-2B, established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate, an increased rate of extracellular acidification, and inhibition by the non-metabolized glucose analog, 2-deoxy-D-glucose. Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression, as well as protein accumulation of an established glycolysis master-regulator, hypoxia-inducible factor 1A. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases. - Highlights: • Chronic arsenite exposure induces aerobic glycolysis, dubbed the “Warburg effect”. • Arsenite-induced Warburg effect is a general phenomenon in cultured human cells. • HIF-1A may mediate arsenite induced Warburg effect.

Arsenic exposure induces the Warburg effect in cultured human cells

International Nuclear Information System (INIS)

Zhao, Fei; Severson, Paul; Pacheco, Samantha; Futscher, Bernard W.; Klimecki, Walter T.

2013-01-01

Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure to arsenite (75 ppb) is sufficient to induce aerobic glycolysis (the Warburg effect) as a generalized phenomenon in cultured human primary cells and cell lines. Expanded studies in one such cell line, the non-malignant pulmonary epithelial line, BEAS-2B, established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate, an increased rate of extracellular acidification, and inhibition by the non-metabolized glucose analog, 2-deoxy-D-glucose. Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression, as well as protein accumulation of an established glycolysis master-regulator, hypoxia-inducible factor 1A. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases. - Highlights: • Chronic arsenite exposure induces aerobic glycolysis, dubbed the “Warburg effect”. • Arsenite-induced Warburg effect is a general phenomenon in cultured human cells. • HIF-1A may mediate arsenite induced Warburg effect

The Scourge of Asian Flu: In Utero Exposure to Pandemic Influenza and the Development of a Cohort of British Children

Science.gov (United States)

Kelly, Elaine

2011-01-01

This paper examines the impact of in utero exposure to the Asian influenza pandemic of 1957 upon childhood development. Outcome data are provided by the National Child Development Study (NCDS), a panel study where all members were potentially exposed in the womb. Epidemic effects are identified using geographic variation in a surrogate measure of…

In Utero DDT and DDE Exposure and Obesity Status of 7-Year-Old Mexican-American Children in the CHAMACOS Cohort

Science.gov (United States)

Schall, Raul Aguilar; Harley, Kim G.; Bradman, Asa; Barr, Dana; Eskenazi, Brenda

2013-01-01

Background: In utero exposure to endocrine disrupting compounds including dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) has been hypothesized to increase risk of obesity later in life. Objectives: The Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study is a longitudinal birth cohort of low-income Latinas living in a California agricultural community. We examined the relation of in utero DDT and DDE exposure to child obesity at 7 years of age. We also examined the trend with age (2, 3.5, 5, and 7 years) in the exposure–obesity relation. Methods: We included 270 children with o,p´-DDT, p,p´-DDT, and p,p´-DDE concentrations measured in maternal serum during pregnancy (nanograms per gram lipid) and complete 7-year follow-up data including weight (kilograms) and height (centimeters). Body mass index (BMI; kilograms per meter squared) was calculated and obesity was defined as ≥ 95th percentile on the sex-specific BMI-for-age Centers for Disease Control and Prevention 2000 growth charts. Results: At 7 years, 96 (35.6%) children were obese. A 10-fold increase in o,p´-DDT, p,p´-DDT, or p,p´-DDE, was nonsignificantly associated with increased odds (OR) of obesity [o,p´-DDT adjusted (adj-) OR = 1.17, 95% CI: 0.75, 1.82; p,p´-DDT adj-OR = 1.19, 95% CI: 0.81, 1.74; p,p´-DDE adj-OR = 1.22, 95% CI: 0.72, 2.06]. With increasing age at follow-up, we observed a significant trend toward a positive association between DDT and DDE exposure and odds of obesity. Conclusion: We did not find a significant positive relation between in utero DDT and DDE exposure and obesity status of 7-year-old children. However, given the observed trend with age, continued follow-up will be informative. PMID:23512307

Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

International Nuclear Information System (INIS)

Stueckle, Todd A.; Lu, Yongju; Davis, Mary E.; Wang, Liying; Jiang, Bing-Hua; Holaskova, Ida; Schafer, Rosana; Barnett, John B.; Rojanasakul, Yon

2012-01-01

Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As 2 O 3

Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Stueckle, Todd A., E-mail: tstueckle@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Lu, Yongju, E-mail: yongju6@hotmail.com [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Davis, Mary E., E-mail: mdavis@wvu.edu [Department of Physiology, West Virginia University, Morgantown, WV 26506 (United States); Wang, Liying, E-mail: lmw6@cdc.gov [Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Jiang, Bing-Hua, E-mail: bhjiang@jefferson.edu [Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Holaskova, Ida, E-mail: iholaskova@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Schafer, Rosana, E-mail: rschafer@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Barnett, John B., E-mail: jbarnett@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Rojanasakul, Yon, E-mail: yrojan@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States)

2012-06-01

Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As{sub 2}O

[Arsenical keratosis treated by dermatome shaving].

Science.gov (United States)

Kjerkegaard, Ulrik Knap; Heje, Jens Martin; Vestergaard, Christian; Stausbøl-Grøn, Birgitte; Stolle, Lars Bjørn

2014-05-05

Cutaneous malignancy in association with arsenic exposure is a rare but well-documented phenomenon. Signs of chronic arsenic exposure are very rare in Denmark today. However, arsenic was used in the medical treatment of psoriasis vulgaris up till the 1980's and several patients suffer from this arsenic treatment today. This case report shows that arsenical keratosis can be treated by dermatome shaving, a superficial destructive therapy.

Urinary 8-hydroxydeoxyguanosine and urothelial carcinoma risk in low arsenic exposure area

International Nuclear Information System (INIS)

Chung, C.-J.; Huang, C.-J.; Pu, Y.-S.; Su, C.-T.; Huang, Y.-K.; Chen, Y.-T.; Hsueh, Y.-M.

2008-01-01

Arsenic is a well-documented human carcinogen and is known to cause oxidative stress in cultured cells and animals. A hospital-based case-control study was conducted to evaluate the relationship among the levels of urinary 8-hydroxydeoxyguanosine (8-OHdG), the arsenic profile, and urothelial carcinoma (UC). Urinary 8-OHdG was measured by using high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. The urinary species of inorganic arsenic and their metabolites were analyzed by high-performance liquid chromatography (HPLC) and hydride generator-atomic absorption spectrometry (HG-AAS). This study showed that the mean urinary concentration of total arsenics was significantly higher, at 37.67 ± 2.98 μg/g creatinine, for UC patients than for healthy controls of 21.10 ± 0.79 μg/g creatinine (p < 0.01). Urinary 8-OHdG levels correlated with urinary total arsenic concentrations (r = 0.19, p < 0.01). There were significantly higher 8-OHdG levels, of 7.48 ± 0.97 ng/mg creatinine in UC patients, compared to healthy controls of 5.95 ± 0.21 ng/mg creatinine. Furthermore, female UC patients had higher 8-OHdG levels of 9.22 ± 0.75 than those of males at 5.76 ± 0.25 ng/mg creatinine (p < 0.01). Multiple linear regression analyses revealed that high urinary 8-OHdG levels were associated with increased total arsenic concentrations, inorganic arsenite, monomethylarsonic acid (MMA), and dimethylarsenate (DMA) as well as the primary methylation index (PMI) even after adjusting for age, gender, and UC status. The results suggest that oxidative DNA damage was associated with arsenic exposure, even at low urinary level of arsenic

Chronic natural arsenic exposure affecting histoarchitecture of gonads in Black Bengal goats (Capra aegagrushircus

Directory of Open Access Journals (Sweden)

Md. Abdul Wares

2015-06-01

Full Text Available Arsenic is a major water pollutant that may cause serious health hazard (e.g., infertility in human and animal. We evaluated the changes in histoarchitecture of testes and ovaries of adult Black Bengal goats (n=10 reared in arsenic affected areas in Bangladesh. Grossly, we found insignificant variations among the testes and ovaries, but histological evaluation revealed an extensive alteration in morphology of both testes and ovaries in the arsenic affected goats. In testes, the thickening of tunica albugenia and trabeculae, widening of intertubular space between seminiferous tubules, and narrowing in diameter of seminiferous tubules were observed. In ovaries of arsenic affected goats, significant decrease in number of primary follicles and antral follicles were observed. The diameters of secondary and antral follicles were significantly reduced. The granulosa layer of antral follicles showed marked thickening. The findings indicate that chronic arsenic exposure alters the histoarchitecture of both male and female gonads in Black Bengal goat, and thereby may affect their reproductive performance.

Understanding Arsenic Dynamics in Agronomic Systems to ...

Science.gov (United States)

This review is on arsenic in agronomic systems, and covers processes that influence the entry of arsenic into the human food supply. The scope is from sources of arsenic (natural and anthropogenic) in soils, biogeochemical and rhizosphere processes that control arsenic speciation and availability, through to mechanisms of uptake by crop plants and potential mitigation strategies. This review makes a case for taking steps to prevent or limit crop uptake of arsenic, wherever possible, and to work toward a long-term solution to the presence of arsenic in agronomic systems. The past two decades have seen important advances in our understanding of how biogeochemical and physiological processes influence human exposure to soil arsenic, and thus must now prompt an informed reconsideration and unification of regulations to protect the quality of agricultural and residential soils. Consumption of staple foods such as rice, beverages such as apple juice, or vegetables grown in historically arsenic-contaminated soils is now recognized as a tangible route of arsenic exposure that, in many cases, is more significant than exposure from drinking water. Understanding the sources of arsenic to crop plants and the factors that influence them is key to reducing exposure now and preventing exposure in future. In addition to the abundant natural sources of arsenic, there are a large number of industrial and agricultural sources of arsenic to the soil; from mining wastes, coal fly

Association of arsenic, cadmium and manganese exposure with neurodevelopment and behavioural disorders in children: A systematic review and meta-analysis

International Nuclear Information System (INIS)

Rodríguez-Barranco, Miguel; Lacasaña, Marina; Aguilar-Garduño, Clemente; Alguacil, Juan; Gil, Fernando; González-Alzaga, Beatriz; Rojas-García, Antonio

2013-01-01

The aim of this study was to analyse the scientific evidence published to date on the potential effects on neurodevelopment and behavioural disorders in children exposed to arsenic, cadmium and manganese and to quantify the magnitude of the effect on neurodevelopment by pooling the results of the different studies. We conducted a systematic review of original articles from January 2000 until March 2012, that evaluate the effects on neurodevelopment and behavioural disorders due to pre or post natal exposure to arsenic, cadmium and manganese in children up to 16 years of age. We also conducted a meta-analysis assessing the effects of exposure to arsenic and manganese on neurodevelopment. Forty-one articles that evaluated the effects of metallic elements on neurodevelopment and behavioural disorders met the inclusion criteria: 18 examined arsenic, 6 cadmium and 17 manganese. Most studies evaluating exposure to arsenic (13 of 18) and manganese (14 of 17) reported a significant negative effect on neurodevelopment and behavioural disorders. Only two studies that evaluated exposure to cadmium found an association with neurodevelopmental or behavioural disorders. The results of our meta-analysis suggest that a 50% increase of arsenic levels in urine would be associated with a 0.4 decrease in the intelligence quotient (IQ) of children aged 5–15 years. Moreover a 50% increase of manganese levels in hair would be associated with a decrease of 0.7 points in the IQ of children aged 6–13 years. There is evidence that relates arsenic and manganese exposure with neurodevelopmental problems in children, but there is little information on cadmium exposure. Few studies have evaluated behavioural disorders due to exposure to these compounds, and manganese is the only one for which there is more evidence of the existence of association with attention deficit disorder with hyperactivity. - Highlights: • We evaluated the association between As, Cd and Mn with neurodevelopment in

Association of arsenic, cadmium and manganese exposure with neurodevelopment and behavioural disorders in children: A systematic review and meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Rodríguez-Barranco, Miguel [Andalusian School of Public Health (EASP), Granada (Spain); Lacasaña, Marina, E-mail: marina.lacasana.easp@juntadeandalucia.es [Andalusian School of Public Health (EASP), Granada (Spain); CIBER of Epidemiology and Public Health (CIBERESP), Madrid (Spain); Aguilar-Garduño, Clemente [CIBER of Epidemiology and Public Health (CIBERESP), Madrid (Spain); Centre Superior d' Investigació en Salut Pública, Conselleria de Sanitat, Valencia (Spain); Alguacil, Juan [CIBER of Epidemiology and Public Health (CIBERESP), Madrid (Spain); Department of Environmental Biology and Public Health, University of Huelva, Huelva (Spain); Gil, Fernando [Department of Legal Medicine and Toxicology, University of Granada, Granada (Spain); González-Alzaga, Beatriz [Andalusian School of Public Health (EASP), Granada (Spain); Rojas-García, Antonio [CIBER of Epidemiology and Public Health (CIBERESP), Madrid (Spain)

2013-06-01

The aim of this study was to analyse the scientific evidence published to date on the potential effects on neurodevelopment and behavioural disorders in children exposed to arsenic, cadmium and manganese and to quantify the magnitude of the effect on neurodevelopment by pooling the results of the different studies. We conducted a systematic review of original articles from January 2000 until March 2012, that evaluate the effects on neurodevelopment and behavioural disorders due to pre or post natal exposure to arsenic, cadmium and manganese in children up to 16 years of age. We also conducted a meta-analysis assessing the effects of exposure to arsenic and manganese on neurodevelopment. Forty-one articles that evaluated the effects of metallic elements on neurodevelopment and behavioural disorders met the inclusion criteria: 18 examined arsenic, 6 cadmium and 17 manganese. Most studies evaluating exposure to arsenic (13 of 18) and manganese (14 of 17) reported a significant negative effect on neurodevelopment and behavioural disorders. Only two studies that evaluated exposure to cadmium found an association with neurodevelopmental or behavioural disorders. The results of our meta-analysis suggest that a 50% increase of arsenic levels in urine would be associated with a 0.4 decrease in the intelligence quotient (IQ) of children aged 5–15 years. Moreover a 50% increase of manganese levels in hair would be associated with a decrease of 0.7 points in the IQ of children aged 6–13 years. There is evidence that relates arsenic and manganese exposure with neurodevelopmental problems in children, but there is little information on cadmium exposure. Few studies have evaluated behavioural disorders due to exposure to these compounds, and manganese is the only one for which there is more evidence of the existence of association with attention deficit disorder with hyperactivity. - Highlights: • We evaluated the association between As, Cd and Mn with neurodevelopment in

Napoleon Bonaparte's exposure to arsenic during 1816.

Science.gov (United States)

Leslie, A C; Smith, H

1978-12-11

Analysis of hair from Napoleon showed that he was exposed to considerable amounts of arsenic during 1816. The distribution pattern of the arsenic in the hair is similar to that found after the daily ingestion of excessive amounts of arsenic.

Altered Gene Expression by Low-Dose Arsenic Exposure in Humans and Cultured Cardiomyocytes: Assessment by Real-Time PCR Arrays

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Judy Mumford

2011-06-01

Full Text Available Chronic arsenic exposure results in higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects on expression of selected genes in the blood lymphocytes from 159 people exposed chronically to arsenic in their drinking water using a novel RT-PCR TaqMan low-density array (TLDA. We found that expression of tumor necrosis factor-α (TNF-α, which activates both inflammation and NF-κB-dependent survival pathways, was strongly associated with water and urinary arsenic levels. Expression of KCNA5, which encodes a potassium ion channel protein, was positively associated with water and toe nail arsenic levels. Expression of 2 and 11 genes were positively associated with nail and urinary arsenic, respectively. Because arsenic exposure has been reported to be associated with long QT intervals and vascular disease in humans, we also used this TLDA for analysis of gene expression in human cardiomyocytes exposed to arsenic in vitro. Expression of the ion-channel genes CACNA1, KCNH2, KCNQ1 and KCNE1 were down-regulated by 1-mM arsenic. Alteration of some common pathways, including those involved in oxidative stress, inflammatory signaling, and ion-channel function, may underlay the seemingly disparate array of arsenic-associated diseases, such as cancer, cardiovascular disease, and diabetes.

Arsenic metabolism efficiency has a causal role in arsenic toxicity: Mendelian randomization and gene-environment interaction.

Science.gov (United States)

Pierce, Brandon L; Tong, Lin; Argos, Maria; Gao, Jianjun; Farzana, Jasmine; Roy, Shantanu; Paul-Brutus, Rachelle; Rahaman, Ronald; Rakibuz-Zaman, Muhammad; Parvez, Faruque; Ahmed, Alauddin; Quasem, Iftekhar; Hore, Samar K; Alam, Shafiul; Islam, Tariqul; Harjes, Judith; Sarwar, Golam; Slavkovich, Vesna; Gamble, Mary V; Chen, Yu; Yunus, Mohammad; Rahman, Mahfuzar; Baron, John A; Graziano, Joseph H; Ahsan, Habibul

2013-12-01

Arsenic exposure through drinking water is a serious global health issue. Observational studies suggest that individuals who metabolize arsenic efficiently are at lower risk for toxicities such as arsenical skin lesions. Using two single nucleotide polymorphisms(SNPs) in the 10q24.32 region (near AS3MT) that show independent associations with metabolism efficiency, Mendelian randomization can be used to assess whether the association between metabolism efficiency and skin lesions is likely to be causal. Using data on 2060 arsenic-exposed Bangladeshi individuals, we estimated associations for two 10q24.32 SNPs with relative concentrations of three urinary arsenic species (representing metabolism efficiency): inorganic arsenic (iAs), monomethylarsonic acid(MMA) and dimethylarsinic acid (DMA). SNP-based predictions of iAs%, MMA% and DMA% were tested for association with skin lesion status among 2483 cases and 2857 controls. Causal odds ratios for skin lesions were 0.90 (95% confidence interval[CI]: 0.87, 0.95), 1.19 (CI: 1.10, 1.28) and 1.23 (CI: 1.12, 1.36)for a one standard deviation increase in DMA%, MMA% and iAs%,respectively. We demonstrated genotype-arsenic interaction, with metabolism-related variants showing stronger associations with skin lesion risk among individuals with high arsenic exposure (synergy index: 1.37; CI: 1.11, 1.62). We provide strong evidence for a causal relationship between arsenic metabolism efficiency and skin lesion risk. Mendelian randomization can be used to assess the causal role of arsenic exposure and metabolism in a wide array of health conditions.exposure and metabolism in a wide array of health conditions.Developing interventions that increase arsenic metabolism efficiency are likely to reduce the impact of arsenic exposure on health.

Testicular steroidogenesis is not altered by 137 cesium Chernobyl fallout, following in utero or post-natal chronic exposure.

Science.gov (United States)

Grignard, Elise; Guéguen, Yann; Grison, Stéphane; Dublineau, Isabelle; Gourmelon, Patrick; Souidi, Maâmar

2010-05-01

The testis is especially sensitive to pollutants, including radionuclides. Following the Chernobyl nuclear power plant accident, several of these radionuclides were emitted and spread in the environment. Subsequently, children presented some disruptions of the endocrine system. To determine whether these disruptions were due to 137 cesium ((137)Cs) exposure, the effects of chronic contamination with low doses of (137)Cs in utero or from birth on testicular steroidogenesis in rats were studied. Contamination was continued for 9 months. No modification was observed in circulating level of hormones (17beta-estradiol, testosterone, follicle-stimulating hormone, luteinizing hormone) following in utero or post-natal contamination. Expression of several genes involved in testicular steroidogenesis was affected (cyp19a1, fxr, sf-1), without modification of protein expression or activity. Our results suggest that growing organisms may be affected at the molecular level by (137)Cs contamination at this post-accidental dose. Copyright 2010 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Urinary Arsenic Metabolites of Subjects Exposed to Elevated Arsenic Present in Coal in Shaanxi Province, China

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Linsheng Yang

2011-06-01

Full Text Available In contrast to arsenic (As poisoning caused by naturally occurring inorganic arsenic-contaminated water consumption, coal arsenic poisoning (CAP induced by elevated arsenic exposure from coal combustion has rarely been reported. In this study, the concentrations and distributions of urinary arsenic metabolites in 57 volunteers (36 subjects with skin lesions and 21 subjects without skin lesions, who had been exposed to elevated levels of arsenic present in coal in Changshapu village in the south of Shaanxi Province (China, were reported. The urinary arsenic species, including inorganic arsenic (iAs [arsenite (iAsIII and arsenate (iAsV], monomethylarsonic acid (MMAV and dimethylarsinic acid (DMAV, were determined by high-performance liquid chromatography (HPLC combined with inductively coupled plasma mass spectroscopy (ICP-MS. The relative distributions of arsenic species, the primary methylation index (PMI = MMAV/iAs and the secondary methylation index (SMI = DMAV/MMAV were calculated to assess the metabolism of arsenic. Subjects with skin lesions had a higher concentration of urinary arsenic and a lower arsenic methylation capability than subjects without skin lesions. Women had a significantly higher methylation capability of arsenic than men, as defined by a higher percent DMAV and SMI in urine among women, which was the one possible interpretation of women with a higher concentration of urinary arsenic but lower susceptibility to skin lesions. The findings suggested that not only the dose of arsenic exposure but also the arsenic methylation capability have an impact on the individual susceptibility to skin lesions induced by coal arsenic exposure.

Toxic Substances Portal- Arsenic

Science.gov (United States)

... is found at low levels in breast milk. top How can families reduce their risk for exposure to arsenic? If you use arsenic-treated wood in home projects, you should wear dust masks, gloves, and protective clothing to decrease exposure to sawdust. ...

Arsenic in private well water part 3 of 3: Socioeconomic vulnerability to exposure in Maine and New Jersey.

Science.gov (United States)

Flanagan, Sara V; Spayd, Steven E; Procopio, Nicholas A; Marvinney, Robert G; Smith, Andrew E; Chillrud, Steven N; Braman, Stuart; Zheng, Yan

2016-08-15

Arsenic is a naturally occurring toxic element often concentrated in groundwater at levels unsafe for human consumption. Private well water in the United States is mostly unregulated by federal and state drinking water standards. It is the responsibility of the over 13 million U.S. households regularly depending on private wells for their water to ensure it is safe for drinking. There is a consistent graded association with health outcomes at all levels of socioeconomic status (SES) in the U.S. Differential exposure to environmental risk may be contributing to this persistent SES-health gradient. Environmental justice advocates cite overwhelming evidence that income and other SES measures are consistently inversely correlated with exposure to suboptimal environmental conditions including pollutants, toxins, and their impacts. Here we use private well household surveys from two states to investigate the association between SES and risks for arsenic exposure, examining the potentially cumulative effects of residential location, testing and treatment behavior, and psychological factors influencing behavior. We find that the distribution of natural arsenic hazard in the environment is socioeconomically random. There is no evidence that higher SES households are avoiding areas with arsenic or that lower SES groups are disproportionately residing in areas with arsenic. Instead, disparities in exposure arise from differing rates of protective action, primarily testing well water for arsenic, and secondly treating or avoiding contaminated water. We observe these SES disparities in behavior as well as in the psychological factors that are most favorable to these behaviors. Assessment of risk should not be limited to the spatial occurrence of arsenic alone. It is important that social vulnerability factors are incorporated into risk modeling and identifying priority areas for intervention, which should include strategies that specifically target socioeconomically vulnerable

Health condition of children irradiated in utero

Energy Technology Data Exchange (ETDEWEB)

Stepanova, E [Research Center for Radiation Medicine, Kiev (Ukraine)

1997-09-01

Among the children exposed to ionizing radiation, the ones irradiated in utero constitute a group under special surveillance. The greatest sensitivity of the organism to the effects of radiative factors occurs in the neonatal period of development and the forthcoming life span with irradiation effects is the longest for these children. Children with acute exposure, with chronic exposure and control group were encompassed by this study - 1144 children altogether. 9 figs, 2 tabs.

Health condition of children irradiated in utero

International Nuclear Information System (INIS)

Stepanova, E.

1997-01-01

Among the children exposed to ionizing radiation, the ones irradiated in utero constitute a group under special surveillance. The greatest sensitivity of the organism to the effects of radiative factors occurs in the neonatal period of development and the forthcoming life span with irradiation effects is the longest for these children. Children with acute exposure, with chronic exposure and control group were encompassed by this study - 1144 children altogether. 9 figs, 2 tabs

Influence of cooking method on arsenic retention in cooked rice related to dietary exposure.

Science.gov (United States)

Rahman, M Azizur; Hasegawa, H; Rahman, M Arifur; Rahman, M Mahfuzur; Miah, M A Majid

2006-10-15

Arsenic concentration in raw rice is not only the determinant in actual dietary exposure. Though there have been many reports on arsenic content in raw rice and different tissues of rice plant, little is known about arsenic content retained in cooked rice after being cooked following the traditional cooking methods employed by the people of arsenic epidemic areas. A field level experiment was conducted in Bangladesh to investigate the influence of cooking methods on arsenic retention in cooked rice. Rice samples were collected directly from a severely arsenic affected area and also from an unaffected area, to compare the results. Rice was cooked according to the traditional methods employed by the population of subjected areas. Arsenic concentrations were 0.40+/-0.03 and 0.58+/-0.12 mg/kg in parboiled rice of arsenic affected area, cooked with excess water and 1.35+/-0.04 and 1.59+/-0.07 mg/kg in gruel for BRRI dhan28 and BRRI hybrid dhan1, respectively. In non-parboiled rice, arsenic concentrations were 0.39+/-0.04 and 0.44+/-0.03 mg/kg in rice cooked with excess water and 1.62+/-0.07 and 1.74+/-0.05 mg/kg in gruel for BRRI dhan28 and BRRI hybrid dhan1, respectively. Total arsenic content in rice, cooked with limited water (therefore gruel was absorbed completely by rice) were 0.89+/-0.07 and 1.08+/-0.06 mg/kg (parboiled) and 0.75+/-0.04 and 1.09+/-0.06 mg/kg (non-parboiled) for BRRI dhan28 and BRRI hybrid dhan1, respectively. Water used for cooking rice contained 0.13 and 0.01 mg of As/l for contaminated and non-contaminated areas, respectively. Arsenic concentrations in cooked parboiled and non-parboiled rice and gruel of non-contaminated area were significantly lower (p<0.01) than that of contaminated area. The results imply that cooking of arsenic contaminated rice with arsenic contaminated water increases its concentration in cooked rice.

Reduction of in utero lead exposures in South African populations: Positive impact of unleaded petrol.

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Halina B Röllin

Full Text Available Prenatal exposure to lead (Pb has been shown to have negative and irreversible health impacts on foetal and early childhood development, affecting morbidity and mortality in adulthood. This study aimed to assess in utero Pb exposure, examine birth outcomes, and identify confounding factors in the large cohort of South African population, following the legislated removal of Pb from petrol.Lead was measured in the maternal blood, urine and cord blood using Inductive Coupled Plasma Mass spectrometry (ICP-MS. The statistical analyses included Spearman's correlation, Wilcoxon rank sum (Mann Whitney, Kruskal-Wallis rank tests and multivariate linear regression.Overall, the geometric mean (GM of Pb in maternal blood (PbB was 1.32 μg/dL (n = 640; 95% CI, 1.24-1.40. In the subset cohort, the GM of paired maternal PbB and cord blood (PbC was 1.73 μg/dL (n = 350; 95% CI, 1.60-1.86 and 1.26 μg/dL (n = 317; 95% CI, 1.18-1.35, respectively with a positive correlation between the log PbB and the log PbC (rho = 0.65, p = <0.001. Birth outcomes showed geographical differences in the gestational age (p<0.001, birth length (p = 0.028 and head circumference (p<0.001, Apgar score at 5 min (p<0.001 and parity (p<0.002. In female neonates, a positive association was found between PbC and head circumference (rho = 0.243; p<0.016. The maternal PbB levels were positively correlated with race, educational status, water sources, cooking fuels and use of pesticides at home.This study has demonstrated not only the positive impact that the introduction of unleaded petrol and lead-free paint has had on in utero exposure to Pb in South Africa, but has also contributed new data on the topic, in a region where such data and scientific investigations in this field are lacking. Future research should evaluate if similar effects can be detected in young children and the adult population.

Persistent Exposure to Arsenic via Drinking Water in Rural Bangladesh Despite Major Mitigation Efforts

Science.gov (United States)

Gardner, Renee; Hamadani, Jena; Grandér, Margaretha; Tofail, Fahmida; Nermell, Barbro; Palm, Brita; Kippler, Maria

2011-01-01

Objectives. Elevated arsenic levels in tube-well water in Bangladesh have prompted extensive mitigation projects. We evaluated the effectiveness of long-term mitigation efforts by longitudinally measuring arsenic exposure in pregnant women and their children, the most susceptible population groups. Methods. The study was nested in a population-based nutrition intervention in Matlab, Bangladesh. Mother–child pairs (n = 1951) were followed from 2001 to 2003, beginning in early gestation and continuing to 5 years postpartum. We measured arsenic concentrations in urine (U-As) of the 5-year-old children by using high-performance liquid chromatography online with hydride generation and inductively coupled plasma mass spectrometry and compared them with earlier childhood U-As and maternal U-As during pregnancy. Results. Children had elevated U-As at 5 years old (median = 51 μg/L, 5th–95th percentiles = 16–355 μg/L), and U-As distribution was similar to that observed in the mothers during gestation. Children's U-As at 5 years old significantly correlated with their U-As at 1.5 years old and to maternal U-As during early and late gestation. Conclusions. Despite major mitigation efforts, arsenic exposure remains highly elevated in rural Bangladesh. Further mitigation strategies are required and must be rigorously evaluated for long-term efficacy. PMID:21778503

The Role of Arsenic Speciation in Dietary Exposure Assessment and the Need to Include Bioaccessibility and Biotransformation

Science.gov (United States)

Chemical form specific exposure assessment for arsenic has long been identified as a source of uncertainty in estimating the risk associated with the aggregate exposure for a population. Some speciation based assessments document occurrence within an exposure route; however, the...

Predicting arsenic concentrations in groundwater of San Luis Valley, Colorado: implications for individual-level lifetime exposure assessment.

Science.gov (United States)

James, Katherine A; Meliker, Jaymie R; Buttenfield, Barbara E; Byers, Tim; Zerbe, Gary O; Hokanson, John E; Marshall, Julie A

2014-08-01

Consumption of inorganic arsenic in drinking water at high levels has been associated with chronic diseases. Risk is less clear at lower levels of arsenic, in part due to difficulties in estimating exposure. Herein we characterize spatial and temporal variability of arsenic concentrations and develop models for predicting aquifer arsenic concentrations in the San Luis Valley, Colorado, an area of moderately elevated arsenic in groundwater. This study included historical water samples with total arsenic concentrations from 595 unique well locations. A longitudinal analysis established temporal stability in arsenic levels in individual wells. The mean arsenic levels for a random sample of 535 wells were incorporated into five kriging models to predict groundwater arsenic concentrations at any point in time. A separate validation dataset (n = 60 wells) was used to identify the model with strongest predictability. Findings indicate that arsenic concentrations are temporally stable (r = 0.88; 95 % CI 0.83-0.92 for samples collected from the same well 15-25 years apart) and the spatial model created using ordinary kriging best predicted arsenic concentrations (ρ = 0.72 between predicted and observed validation data). These findings illustrate the value of geostatistical modeling of arsenic and suggest the San Luis Valley is a good region for conducting epidemiologic studies of groundwater metals because of the ability to accurately predict variation in groundwater arsenic concentrations.

Understanding arsenic metabolism through spectroscopic determination of arsenic in human urine

OpenAIRE

Brima, Eid I.; Jenkins, Richard O.; Haris, Parvez I.

2006-01-01

In this review we discuss a range of spectroscopic techniques that are currently used for analysis of arsenic in human urine for understanding arsenic metabolism and toxicity, especially in relation to genetics/ethnicity, ingestion studies and exposure to arsenic through drinking water and diet. Spectroscopic techniques used for analysis of arsenic in human urine include inductively coupled plasma mass spectrometry (ICP-MS), hydride generation atomic absorption spectrometry (HG-AAS), hydride ...

ARSENIC SPECIATION ANALYSIS IN HUMAN SALIVA

Science.gov (United States)

Background: Determination of arsenic species in human saliva is potentially useful for biomonitoring of human exposure to arsenic and for studying arsenic metabolism. However, there is no report on the speciation analysis of arsenic in saliva. Methods: Arsenic species in saliva ...

Review of arsenic contamination and human exposure through water food in rural areas in Vietnam

Energy Technology Data Exchange (ETDEWEB)

Hahn, Celia

2016-05-01

The Red River Delta in Vietnam is one of the regions whose quaternary aquifers are polluted by arsenic. Chronic toxification by arsenic can cause severe illnesses such as cancer, skin lesions, developmental defects, cardiovascular and neurological diseases, and diabetes. In this study, a food processing craft village in the Red River Delta was investigated regarding the potential risk faced by the population due to arsenic. The potential sources of arsenic are the groundwater, the crops grown in the surroundings, and animal products from local husbandry. However, the occurrence of arsenic in nature is variable, and its bioavailability and toxicity depend very much on its specification: trivalent compounds are more toxic and often more mobile than pentavalent compounds, while inorganic species are generally more toxic than organic ones. Local conditions, such as the redox potential, strongly influence its specification and thus potential bioavailability. The introduction to this work elucidates the key factors which potentially cause human exposure to arsenic: the geological setting of the study area, land and water use patterns, and the current state of research regarding the mobilization, bioavailability and plant uptake of arsenic. Although the study area is located in a region where the groundwater is known to be moderately contaminated by arsenic, the level of arsenic in the groundwater in the village had not previously been determined. In this study, water use in the village was examined by a survey among the farmers and by water analyses, which are presented in the following chapters. Four main water sources (rain, river, tube well and a public municipal waterworks) are used for the different daily activities; the highest risk to human health was found to be the bore well water, which is pumped from the shallow Holocene aquifer. The water from the bore wells is commonly used for cleaning and washing as well as to feed the animals and for food processing

Review of arsenic contamination and human exposure through water food in rural areas in Vietnam

International Nuclear Information System (INIS)

Hahn, Celia

2016-01-01

The Red River Delta in Vietnam is one of the regions whose quaternary aquifers are polluted by arsenic. Chronic toxification by arsenic can cause severe illnesses such as cancer, skin lesions, developmental defects, cardiovascular and neurological diseases, and diabetes. In this study, a food processing craft village in the Red River Delta was investigated regarding the potential risk faced by the population due to arsenic. The potential sources of arsenic are the groundwater, the crops grown in the surroundings, and animal products from local husbandry. However, the occurrence of arsenic in nature is variable, and its bioavailability and toxicity depend very much on its specification: trivalent compounds are more toxic and often more mobile than pentavalent compounds, while inorganic species are generally more toxic than organic ones. Local conditions, such as the redox potential, strongly influence its specification and thus potential bioavailability. The introduction to this work elucidates the key factors which potentially cause human exposure to arsenic: the geological setting of the study area, land and water use patterns, and the current state of research regarding the mobilization, bioavailability and plant uptake of arsenic. Although the study area is located in a region where the groundwater is known to be moderately contaminated by arsenic, the level of arsenic in the groundwater in the village had not previously been determined. In this study, water use in the village was examined by a survey among the farmers and by water analyses, which are presented in the following chapters. Four main water sources (rain, river, tube well and a public municipal waterworks) are used for the different daily activities; the highest risk to human health was found to be the bore well water, which is pumped from the shallow Holocene aquifer. The water from the bore wells is commonly used for cleaning and washing as well as to feed the animals and for food processing

Exposure to inorganic arsenic is associated with increased mitochondrial DNA copy number and longer telomere length in peripheral blood.

Directory of Open Access Journals (Sweden)

Syeda Shegufta Ameer

2016-08-01

Full Text Available Background: Exposure to inorganic arsenic (iAs through drinking water causes cancer. Alterations in mitochondrial DNA copy number (mtDNAcn and telomere length in blood have been associated with cancer risk. We elucidated if arsenic exposure alters mtDNAcn and telomere length in individuals with different arsenic metabolizing capacity.Methods: We studied two groups in the Salta province, Argentina, one in the Puna area of the Andes (N=264, 89% females and one in Chaco (N=169, 75% females. We assessed arsenic exposure as the sum of arsenic metabolites [iAs, methylarsonic acid (MMA, dimethylarsinic acid (DMA] in urine (U-As using high-performance liquid chromatography coupled with hydride generation and inductively coupled plasma mass spectrometry. Efficiency of arsenic metabolism was expressed as percentage of urinary metabolites. MtDNAcn and telomere length were determined in blood by real-time PCR. Results: Median U-As was 196 (5 - 95 percentile: 21 - 537 µg/L in Andes and 80 (5 - 95 percentile: 15 - 1637 µg/L in Chaco. The latter study group had less-efficient metabolism, with higher %iAs and %MMA in urine compared with the Andean group. U-As was significantly associated with increased mtDNAcn (log2 transformed to improve linearity in Chaco (β=0.027 per 100 µg/L, p=0.0085; adjusted for age and sex, but not in Andes (β=0.025, p=0.24. U-As was also associated with longer telomere length in Chaco (β=0.016, p=0.0066 and Andes (β=0.0075, p=0.029. In both populations, individuals with above median %iAs showed significantly higher mtDNAcn and telomere length compared with individuals with below median %iAs. Conclusions: Arsenic was associated with increased mtDNAcn and telomere length, particularly in individuals with less-efficient arsenic metabolism, a group who may have increased risk for arsenic-related cancer.

Enhanced urinary bladder and liver carcinogenesis in male CD1 mice exposed to transplacental inorganic arsenic and postnatal diethylstilbestrol or tamoxifen

International Nuclear Information System (INIS)

Waalkes, Michael P.; Liu Jie; Ward, Jerrold M.; Diwan, Bhalchandra A.

2006-01-01

Pregnant CD1 mice received 85 ppm arsenite in the drinking water from gestation day 8 to 18, groups (n = 35) of male offspring were subsequently injected on postpartum days 1 through 5 with diethylstilbestrol (DES; 2 μg/pup/day) or tamoxifen (TAM; 10 μg/pup/day), and tumor formation was assessed over 90 weeks. Arsenic alone increased hepatocellular carcinoma (14%), adenoma (23%) and total tumors (31%) compared to control (0, 2 and 2%, respectively). Arsenic alone also increased lung adenocarcinoma, adrenal cortical adenoma and renal cystic tubular hyperplasia compared to control. Compared to arsenic alone, arsenic plus DES increased liver tumor incidence in mice at risk 2.2-fold and increased liver tumor multiplicity (tumors/liver) 1.8-fold. The treatments alone did not impact urinary bladder carcinogenesis, but arsenic plus TAM significantly increased formation of urinary bladder transitional cell tumors (papilloma and carcinoma; 13%) compared to control (0%). Urinary bladder proliferative lesions (combined tumors and hyperplasia) were also increased by arsenic plus TAM (40%) or arsenic plus DES (43%) compared to control (0%) or the treatments alone. Urinary bladder proliferative lesions occurred in the absence of any evidence of uroepithelial cytotoxic lesions. Urinary bladder lesions and hepatocellular carcinoma induced by arsenic plus TAM and/or DES overexpressed estrogen receptor-α, indicating that aberrant estrogen signaling may have been a factor in the enhanced carcinogenic response. Thus, in male CD1 mice, gestational arsenic exposure alone induced liver adenoma and carcinoma, lung adenocarcinoma, adrenal adenoma and renal cystic hyperplasia. Furthermore, DES enhanced transplacental arsenic-induced hepatocarcinogenesis. In utero arsenic also initiated urinary bladder tumor formation when followed by postnatal TAM and uroepithelial proliferative lesions when followed by TAM or DES

In-utero exposure to smoking, alcohol, coffee, and tea and risk of strabismus

DEFF Research Database (Denmark)

Torp-Pedersen, Tobias; Boyd, Heather A; Poulsen, Gry

2010-01-01

In a prospective, population-based cohort study, the authors investigated the effect of in-utero exposure to maternal smoking and consumption of alcohol, coffee, and tea on the risk of strabismus. They reviewed medical records for children in the Danish National Birth Cohort identified through...... national registers as possibly having strabismus. Relative risk estimates were adjusted for year of birth, social class, maternal smoking, maternal age at birth, and maternal coffee and tea consumption. The authors identified 1,321 cases of strabismus in a cohort of 96,842 Danish children born between 1996.......92, 1.61). Light maternal alcohol consumption was inversely associated with strabismus risk, whereas maternal coffee and tea drinking were not associated with strabismus risk. In conclusion, smoking during pregnancy is associated with an increased risk of strabismus in the offspring. Conversely, light...

In Utero Exposure to Fine Particulate Matter Causes Hypertension Due to Impaired Renal Dopamine D1 Receptor in Offspring

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Zhengmeng Ye

2018-03-01

Full Text Available Background/Aims: Adverse environment in utero can modulate adult phenotypes including blood pressure. Fine particulate matter (PM2.5 exposure in utero causes hypertension in the offspring, but the exact mechanisms are not clear. Renal dopamine D1 receptor (D1R, regulated by G protein-coupled receptor kinase type 4 (GRK4, plays an important role in the regulation of renal sodium transport and blood pressure. In this present study, we determined if renal D1R dysfunction is involved in PM2.5–induced hypertension in the offspring. Methods: Pregnant Sprague–Dawley rats were given an oropharyngeal drip of PM2.5 (1.0 mg/kg at gestation day 8, 10, and 12. The blood pressure, 24-hour sodium excretion, and urine volume were measured in the offspring. The expression levels of GRK4 and D1R were determined by immunoblotting. The phosphorylation of D1R was investigated using immunoprecipitation. Plasma malondialdehyde and superoxide dismutase levels were also measured in the offspring. Results: As compared with saline-treated dams, offspring of PM2.5-treated dams had increased blood pressure, impaired sodium excretion, and reduced D1R-mediated natriuresis and diuresis, accompanied by decreased renal D1R expression and GRK4 expression. The impaired renal D1R function and increased GRK4 expression could be caused by increased reactive oxidative stress (ROS induced by PM2.5 exposure. Administration of tempol, a redox-cycling nitroxide, for 4 weeks in the offspring of PM2.5-treated dam normalized the decreased renal D1R expression and increased renal D1R phosphorylation and GRK4 expression. Furthermore, tempol normalized the increased renal expression of c-Myc, a transcription factor that regulates GRK4 expression. Conclusions: In utero exposure to PM2.5 increases ROS and GRK4 expression, impairs D1R-mediated sodium excretion, and increases blood pressure in the offspring. These studies suggest that normalization of D1R function may be a target for the

Association between occupational exposure to arsenic and neurological, respiratory and renal effects

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Halatek, Tadeusz; Sinczuk-Walczak, Halina; Rabieh, Sasan; Wasowicz, Wojciech

2009-01-01

Occupational exposure by inhalation in copper smelter is associated with several subclinical health phenomena. The respiratory tract is usually involved in the process of detoxication of inhaled noxious agents which, as arsenic, can act as inductors of oxidative stress (Lantz, R.C., Hays, A.M., 2006. Role of oxidative stress in arsenic-induced toxicity. Drug Metab. Rev. 38, 791-804). It is also known that irritating fumes affect distal bronchioles of non-ciliated, epithelial Clara cells, which secrete anti-inflammatory and immunosuppressive Clara cell protein (CC16) into the respiratory tract. The study group comprised 39 smelters employed at different workplaces in a copper foundry, matched for age and smoking habits with the control group (n = 16). Subjective neurological symptoms (SNS), visual evoked potentials (VEP), electroneurographic (EneG) and electroencephalographic (EEG) results were examined in the workers and the relationships between As concentration in the air (As-Air) and urine (As-U) were assessed. Effects of exposure were expressed in terms of biomarkers: CC16 as early pulmonary biomarker and β 2 -microglobulin (β 2 M) in urine and serum and retinol binding protein (RBP) as renal markers, measured by sensitive latex immunoassay. The concentrations of arsenic exceeded about two times the Threshold Limit Values (TLV) (0.01 mg/m 3 ). The contents of lead did not exceed the TLV (0.05 mg/m 3 ). Low CC16 levels in serum (12.1 μg/l) of workers with SNS and VEP symptoms and highest level As-U (x a 39.0 μg/l) were noted earliest in relation to occupational time. Moreover, those effects were associated with increased levels of urinary and serum β 2 M and urinary RBP. Results of our study suggested the initiative key role of oxidative stress in triggering the processes that eventually lead to the subclinical effects of arsenic on the nervous system.

Caffeine in the milk prevents respiratory disorders caused by in utero caffeine exposure in rats.

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Bodineau, Laurence; Saadani-Makki, Fadoua; Jullien, Hugues; Frugière, Alain

2006-01-25

Consequences of postnatal caffeine exposure by the milk on ponto-medullary respiratory disturbances observed following an in utero caffeine exposure were analysed. Ponto-medullary-spinal cord preparations from newborn rats exposed to caffeine during gestation but not after the birth display an increase in respiratory frequency and an exaggeration of the hypoxic respiratory depression compared to not treated preparations. These data suggest that tachypneic and apneic episodes encountered in human newborns whose mother consumed caffeine during pregnancy are due in large part to central effect of caffeine at the ponto-medullary level. Both baseline respiratory frequency increase and emphasis of hypoxic respiratory depression are not encountered if rat dams consumed caffeine during nursing. Our hypothesis is that newborn rats exposed to caffeine during gestation but not after the birth would be in withdrawal situation whereas, when caffeine is present in drinking fluid of lactating dams, it goes down the milk and is able to prevent ponto-medullary respiratory disturbances.

An insight of environmental contamination of arsenic on animal health

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Paramita Mandal

2017-03-01

Full Text Available The main threats to human health from heavy metals are associated with exposure to lead, cadmium, mercury and arsenic. Exposure to arsenic is mainly via intake of food and drinking water, food being the most important source in most populations. Although adverse health effects of heavy metals have been known for a long time, exposure to heavy metals continues and is even increasing in some areas. Long-term exposure to arsenic in drinking-water is mainly related to increased risks of skin cancer, but also some other cancers, as well as other skin lesions such as hyperkeratosis and pigmentation changes. Therefore, measures should be taken to reduce arsenic exposure in the general population in order to minimize the risk of adverse health effects. Animal are being exposed to arsenic through contaminated drinking water, feedstuff, grasses, vegetables and different leaves. Arsenic has been the most common causes of inorganic chemical poisoning in farm animals. Although, sub-chronic and chronic exposure of arsenic do not generally reveal external signs or symptoms in farm animals but arsenic (or metabolites concentrations in blood, hair, hoofs and urine are remained high in animals of arsenic contaminated zones. So it is assumed that concentration of arsenic in blood, urine, hair or milk have been used as biomarkers of arsenic exposure in field animals.

Association between arsenic exposure from drinking water and proteinuria: results from the Health Effects of Arsenic Longitudinal Study

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Chen, Yu; Parvez, Faruque; Liu, Mengling; Pesola, Gene R; Gamble, Mary V; Slavkovich, Vesna; Islam, Tariqul; Ahmed, Alauddin; Hasan, Rabiul; Graziano, Joseph H; Ahsan, Habibul

2011-01-01

Background Proteinuria has been recognized as a marker for an increased risk of chronic renal disease. It is unclear whether arsenic (As) exposure from drinking water is associated with proteinuria. Methods We evaluated the association between As exposure from drinking water and proteinuria in 11 122 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Proteinuria was detected by urinary dipstick tests at baseline and at 2-year intervals. As exposure variables included baseline well As and changes in urinary As during follow-up modelled as time-dependent variables in the analyses. Results At baseline, well As was positively related to prevalence of proteinuria; prevalence odds ratios (PORs) for proteinuria in increasing quintiles of well As (≤7, 8–39, 40–91, 92–179 and 180–864 µg/l) were 1.00 (ref), POR 0.99 [95% confidence interval (CI) 0.77–1.27], POR 1.23 (95% CI 0.97–1.57), POR 1.50 (95% CI 1.18–1.89) and POR 1.59 (95% CI 1.26–2.00) (P for trend 70 and 17–70 µg/l in urinary As over time, respectively, and were POR 1.17 (95% CI 0.97–1.42) and POR 1.42 (95% CI 1.16–1.73) for participants with an increasing level of 16–68 and >68 µg/l in urinary As over time, respectively, compared with the group with relatively little changes in urinary As as the reference group (urinary As −16 to 15 µg/l). Conclusion The findings suggest that there are adverse effects of As exposure on the risk of proteinuria and the effects are modifiable by recent changes in As exposure. PMID:21343184

Altered gene expression by low-dose arsenic exposure in humans and cultured cardiomyocytes: Assessment by real-time PCR array

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Arsenic contamination in drinking water has become a great public health concern worldwide. Chronic arsenic exposure results in higher risk of skin, lung and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects o...

Exposure and bioavailability of arsenic in contaminated soils from the La Parrilla mine, Spain

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Anawar, H. M.; Garcia-Sanchez, A.; Murciego, A.; Buyolo, T.

2006-05-01

Arsenic derived from mining activity may contaminate water, soil and plant ecosystems resulting in human health and ecotoxicological risks. In this study, exposure assessment of arsenic (As) in soil, spoil, pondwater and plants collected from the areas contaminated by mine tailings and spoils in and around the La Parrilla mine, Caceres province, Spain, was carried out using AAS method. Water solubility, bioavailability and soil-plant transfer coefficients of As and phytoremediation potential of plants were determined. Arsenic concentrations varied from 148 to 2,540 mg/kg in soils of site 1 and from 610 to 1,285 mg/kg in site 2 exceeding the guideline limit for agricultural soil (50 mg/kg). Arsenic concentrations in pond waters varied from 8.8 to 101.4 μg/l. High concentrations of water-soluble As in the soils that ranged from 0.10 to 4.71 mg/kg in site 1 and from 0.46 to 4.75 mg/kg in site 2 exceeded the maximum permitted level of water-soluble As (0.04 mg/kg) in agricultural soils. Arsenic concentrations varied from 0.8 to 149.5 mg/kg dry wt in the plants of site 1 and from 2.0 to 10.0 mg/kg in the plants of site 2. Arsenic concentrations in plants increased in the approximate order: Retama sphaerocarpa phytoremediation of As contaminated soils.

A concurrent exposure to arsenic and fluoride from drinking water in Chihuahua, Mexico.

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González-Horta, Carmen; Ballinas-Casarrubias, Lourdes; Sánchez-Ramírez, Blanca; Ishida, María C; Barrera-Hernández, Angel; Gutiérrez-Torres, Daniela; Zacarias, Olga L; Saunders, R Jesse; Drobná, Zuzana; Mendez, Michelle A; García-Vargas, Gonzalo; Loomis, Dana; Stýblo, Miroslav; Del Razo, Luz M

2015-04-24

Inorganic arsenic (iAs) and fluoride (F-) are naturally occurring drinking water contaminants. However, co-exposure to these contaminants and its effects on human health are understudied. The goal of this study was examined exposures to iAs and F- in Chihuahua, Mexico, where exposure to iAs in drinking water has been associated with adverse health effects. All 1119 eligible Chihuahua residents (>18 years) provided a sample of drinking water and spot urine samples. iAs and F- concentrations in water samples ranged from 0.1 to 419.8 µg As/L and from 0.05 to 11.8 mg F-/L. Urinary arsenic (U-tAs) and urinary F- (U-F-) levels ranged from 0.5 to 467.9 ng As/mL and from 0.1 to 14.4 µg F-/mL. A strong positive correlation was found between iAs and F- concentrations in drinking water (rs = 0.741). Similarly, U-tAs levels correlated positively with U-F- concentrations (rs = 0.633). These results show that Chihuahua residents exposed to high iAs concentrations in drinking water are also exposed to high levels of F-, raising questions about possible contribution of F- exposure to the adverse effects that have so far been attributed only to iAs exposure. Thus, investigation of possible interactions between iAs and F- exposures and its related health risks deserves immediate attention.

Cardiovascular risk from water arsenic exposure in Vietnam: Application of systematic review and meta-regression analysis in chemical health risk assessment.

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Phung, Dung; Connell, Des; Rutherford, Shannon; Chu, Cordia

2017-06-01

A systematic review (SR) and meta-analysis cannot provide the endpoint answer for a chemical risk assessment (CRA). The objective of this study was to apply SR and meta-regression (MR) analysis to address this limitation using a case study in cardiovascular risk from arsenic exposure in Vietnam. Published studies were searched from PubMed using the keywords of arsenic exposure and cardiovascular diseases (CVD). Random-effects meta-regression was applied to model the linear relationship between arsenic concentration in water and risk of CVD, and then the no-observable-adverse-effect level (NOAEL) were identified from the regression function. The probabilistic risk assessment (PRA) technique was applied to characterize risk of CVD due to arsenic exposure by estimating the overlapping coefficient between dose-response and exposure distribution curves. The risks were evaluated for groundwater, treated and drinking water. A total of 8 high quality studies for dose-response and 12 studies for exposure data were included for final analyses. The results of MR suggested a NOAEL of 50 μg/L and a guideline of 5 μg/L for arsenic in water which valued as a half of NOAEL and guidelines recommended from previous studies and authorities. The results of PRA indicated that the observed exposure level with exceeding CVD risk was 52% for groundwater, 24% for treated water, and 10% for drinking water in Vietnam, respectively. The study found that systematic review and meta-regression can be considered as an ideal method to chemical risk assessment due to its advantages to bring the answer for the endpoint question of a CRA. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neoplastic and life-span effects of chronic exposure to tritium. II. Rats exposed in utero

International Nuclear Information System (INIS)

Cahill, D.F.; Wright, J.F.; Godbold, J.H.; Ward, J.M.; Laskey, J.W.; Tompkins, E.A.

1975-01-01

A study was conducted to determine the effects on neoplasia incidence and life-span of exposure in utero to a major environmental radionuclide. Sprague-Dawley rats were continuously exposed to tritiated water (HTO) from conception through birth in doses of 0, 1, 10, 50, and 100 μCi HTO/ml body water. HTO administration was terminated at birth. Calculated cumulative doses during gestation were approximately 0, 6.6, 66, 330, and 660 rads of total body irradiation. Under these exposure conditions, the two highest doses resulted in sterile offspring. Animals surviving through 30 days postnatally were defined as the study population and observed until their deaths. Intrauterine exposures to doses up to 66 rads had no significant effects on either sex with respect to lifespan, overall neoplasia incidence, incidence rate, or onset of mammary fibroadenomas. Females exposed to 330 or 660 rads were sterile and had lower incidence rates of mammary fibroadenomas than did controls; at 660 rads females had a lower incidence of overall neoplasia and reduced mean lifespans. Sterile male offspring had reduced mean longevity after irradiation at 660 rads. Regardless of dose group, females had significantly higher incidences of neoplasia and longer life-spans than males

Long-term radiobiological effects in rats after exposure of 131I in utero

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V. V. Talko

2017-12-01

Full Text Available Remote radiobiological effects in male rats prenatally exposed by 131I in different periods of gestation were studied. It was established that the negative effects of irradiation of 131I in utero in the distant period are manifested by disorders of the functioning of the pituitary-thyroid link of endocrine regulation, pro-antioxidant equilibrium, changes in the lipid-lipoprotein spectrum of blood serum. As a result of irradiation of 131I in utero throughout the period of gestation, discoordination in the functioning of the pituitary-thyroid link of endocrine regulation, a violation of the pro-antioxidant balance by increasing the intensity of lipoperoxidation processes and the activity reducing of enzymes of antioxidant defense, the atherogenic orientation of changes in the lipid-lipoprotein spectrum was established. As a result of irradiation by 131I in utero during the third trimester of gestation, the development of hypothyroidism, changes in pro-antioxidant balance due to the activation of antioxidant defense, and the reduction of the concentration of the main classes of lipids have been established.

Arsenic and nicotine co-exposure lead to some synergistic effects on oxidative stress and apoptotic markers in young rat blood, liver, kidneys and brain

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Anshu Jain

2015-01-01

Full Text Available Arsenic and nicotine exposure has been a major health concern globally. Individually both these toxicants increase the risk to various diseases including cancers. However, limited information exists on the co-exposure. In this study, we evaluate the effects of their individual and combined exposure and if co-exposure to these toxicants might have a synergism or antagonism. Male rats were exposed to a very low dose of arsenic (25 ppm in drinking water or nicotine (0.25 mg/kg, sub-cutaneously for a period of 5 months and post exposure various biochemical variables indicative of oxidative stress and apoptosis evaluated. Almost all glutathione linked enzymes showed marked alteration in individual as well as co-exposure treated groups. While serum creatinine and apoptosis indicator, lactate dehydrogenase (LDH were significantly increased in both treatments, an additive effect was noted in co-exposure group. A similar trend was also seen in brain and liver but not in kidneys. Gene expression studies showed marked reduction in catalase, Cu-Zn SOD, GST, there was a significant up regulation in Bax, caspase 3 in various tissues along with urinary 8-OHdG levels, indicative of DNA damage and apoptosis. Interestingly, a decrease in liver arsenic concentration was noted in co-exposed group compared to arsenic alone exposed group. In conclusion, the present study suggests that arsenic and nicotine exhibited significant toxicity during individual exposure whereas co-exposure to these toxins showed variable conditions (indicative of both synergism and antagonism in male rats.

Arsenic exposure triggers a shift in microRNA expression.

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Sturchio, Elena; Colombo, Teresa; Boccia, Priscilla; Carucci, Nicoletta; Meconi, Claudia; Minoia, Claudio; Macino, Giuseppe

2014-02-15

Exposure to inorganic Arsenic (iAs) through drinking water is a major public health problem affecting most countries. iAs has been classified by the International Agency for Research on Cancer as Group 1: "Carcinogenic to humans". Although numerous studies have shown the related adverse effects of iAs, sensitive appropriate biomarkers for studies of environmental epidemiology are still required. The present work aims at investigate the role of microRNAs (miRNAs), powerful negative regulators of gene expression, playing a key role in many physiological and pathological cellular processes, in iAs exposure. To this end, we analyzed miRNA changes in expression profile triggered by iAs exposure in Jurkat cell line. We used microarray technology to profile the expression of miRNAs following 2 μmol/L sodium arsenite treatment at different time points. Moreover, we performed phenotypic analysis of iAs treated cells. Real Time Polymerase Chain Reaction (RT-PCR) was used to validate miRNA microarray data and to assay expression modulation of selected relevant mRNAs. Finally, bioinformatics techniques were applied to reconstruct iAs-relevant molecular pathways and miRNA regulatory networks from the expression data. We report miRNAs modulated after iAs treatment in Jurkat cells. In particular, we highlight 36 miRNAs exhibiting consistent dysregulation and particularly a panel of 8 miRNAs which we also validated by RT-PCR analysis. Computational analysis of lists of putative target genes for these 8 miRNAs points to an involvement in arsenic-response pathways, for a subset of them, that were analyzed by RT-PCR. Furthermore, iAs exposure reveals induction of cell cycle progression and the failure of apoptosis, supporting the idea of iAs carcinogenic activity. Our study provides a list of miRNAs whose expression levels are affected by iAs treatment, corroborating the importance of proceeding with the hunt for specific subset of miRNAs, which can serve as potential biomarkers of

Arsenic Exposure From Drinking Water and the Incidence of CKD in Low to Moderate Exposed Areas of Taiwan: A 14-Year Prospective Study.

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Hsu, Ling-I; Hsieh, Fang-I; Wang, Yuan-Hung; Lai, Tai-Shuan; Wu, Meei-Maan; Chen, Chien-Jen; Chiou, Hung-Yi; Hsu, Kuang-Hung

2017-12-01

Arsenic exposure is associated with decreased kidney function. The association between low to moderate arsenic exposure and kidney disease has not been fully clarified. The association between arsenic exposure from drinking water and chronic kidney disease (CKD) was examined in a long-term prospective observational study. 6,093 participants 40 years and older were recruited from arseniasis-endemic areas in northeastern Taiwan. Arsenic levels were 28.0, 92.8, and 295.7μg/L at the 50th, 75th, and 90th percentiles, respectively. Well-water arsenic and urinary total arsenic (inorganic plus methylated arsenic species) concentrations, adjusted for urinary creatinine concentration. Kidney diseases (ICD-9 codes: 250.4, 274.1, 283.11, 403.*1, 404.*2, 404.*3, 440.1, 442.1, 447.3, or 580-589) and CKD (ICD-9 code: 585) ascertained using Taiwan's National Health Insurance database 1998 to 2011. HRs contrasting CKD risk across arsenic exposure levels were estimated using Cox regression. Prevalence ORs for proteinuria (protein excretion ≥ 200mg/g) comparing quartiles of total urinary arsenic concentrations were estimated using logistic regression. We identified 1,104 incident kidney disease cases, including 447 CKD cases (incidence rates, 166.5 and 67.4 per 10 4 person-years, respectively). A dose-dependent association between well-water arsenic concentrations and kidney diseases was observed after adjusting for age, sex, education, body mass index, cigarette smoking, alcohol consumption, and analgesic use. Using arsenic concentration ≤ 10.0μg/L as reference, multivariable-adjusted HRs for incident CKD were 1.12 (95% CI, 0.88-1.42), 1.33 (95% CI, 1.03-1.72), and 1.33 (95% CI, 1.00-1.77) for arsenic concentrations of 10.1 to 49.9, 50.0 to 149.9, and ≥150.0μg/L, respectively (P for trend=0.02). The association between arsenic concentration and kidney diseases was stronger for women (P for interaction=0.06). Arsenic values in the range of 50th to 75th and 75th to 100th

Urinary arsenic speciation and its correlation with 8-OHdG in Chinese residents exposed to arsenic through coal burning

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Li, X.; Pi, J.B.; Li, B.; Xu, Y.Y.; Jin, Y.P.; Sun, G.F. [China Medical University, Shenyang (China). Dept. for Occupational & Environmental Health

2008-10-15

In contrast to arsenicosis caused by consumption of water contaminated by naturally occurring inorganic arsenic, human exposure to this metalloid through coal burning has been rarely reported. In this study, arsenic speciation and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in urine were determined in the Chinese residents exposed to arsenic through coal burning in Guizhou, China, an epidemic area of chronic arsenic poisoning caused by coal burning. The urinary concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and total arsenic (tAs) of high-arsenic exposed subjects were significantly higher than those of low-arsenic exposed residents. A biomarker of oxidative DNA damage, urinary 8-OHdG level was significantly higher in high-arsenic exposed subjects than that of low exposed. Significant positive correlations were found between 8-OHdG levels and concentrations of iAs, MMA, DMA and tAs, respectively. In addition, a significant negative correlation was observed between 8-OHdG levels and the secondary methylation ratio (DMA/(MMA + DMA)). The results suggest that chronic arsenic exposure through burning coal rich in arsenic is associated with oxidative DNA damages, and that secondary methylation capacity is potentially related to the susceptibility of individuals to oxidative DNA damage induced by arsenic exposure through coal burning in domestic living.

Arsenic and Environmental Health: State of the Science and ...

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Background: Exposure to inorganic and organic arsenic compounds is a major public health problem that affects hundreds of millions of people worldwide. Exposure to arsenic is associated with cancer and noncancer effects in nearly every organ in the body, and evidence is mounting for health effects at lower levels of arsenic exposure than previously thought. Building from a tremendous knowledge base with > 1,000 scientific papers published annually with “arsenic” in the title, the question becomes, what questions would best drive future research directions? Objectives: The objective is to discuss emerging issues in arsenic research and identify data gaps across disciplines. Methods: The National Institutes of Health’s National Institute of Environmental Health Sciences Superfund Research Program convened a workshop to identify emerging issues and research needs to address the multi-faceted challenges related to arsenic and environmental health. This review summarizes information captured during the workshop. Discussion: More information about aggregate exposure to arsenic is needed, including the amount and forms of arsenic found in foods. New strategies for mitigating arsenic exposures and related health effects range from engineered filtering systems to phytogenetics and nutritional interventions. Furthermore, integration of omics data with mechanistic and epidemiological data is a key step toward the goal of linking biomarkers of exposure and suscepti

Arsenic in tube well water in Bangladesh: health and economic impacts and implications for arsenic mitigation.

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Flanagan, Sara V; Johnston, Richard B; Zheng, Yan

2012-11-01

A national drinking water quality survey conducted in 2009 furnished data that were used to make an updated estimate of chronic arsenic exposure in Bangladesh. About 20 million and 45 million people were found to be exposed to concentrations above the national standard of 50 µg/L and the World Health Organization's guideline value of 10 µg/L, respectively. From the updated exposure data and all-cause mortality hazard ratios based on local epidemiological studies, it was estimated that arsenic exposures to concentrations > 50 µg/L and 10-50 µg/L account for an annual 24,000 and perhaps as many as 19,000 adult deaths in the country, respectively. Exposure varies widely in the 64 districts; among adults, arsenic-related deaths account for 0-15% of all deaths. An arsenic-related mortality rate of 1 in every 16 adult deaths could represent an economic burden of 13 billion United States dollars (US$) in lost productivity alone over the next 20 years. Arsenic mitigation should follow a two-tiered approach: (i) prioritizing provision of safe water to an estimated 5 million people exposed to > 200 µg/L arsenic, and (ii) building local arsenic testing capacity. The effectiveness of such an approach was demonstrated during the United Nations Children's Fund 2006-2011 country programme, which provided safe water to arsenic-contaminated areas at a cost of US$ 11 per capita. National scale-up of such an approach would cost a few hundred million US dollars but would improve the health and productivity of the population, especially in future generations.

Immunotoxicity and biodistribution analysis of arsenic trioxide in C57Bl/6 mice following a 2-week inhalation exposure

International Nuclear Information System (INIS)

Burchiel, Scott W.; Mitchell, Leah A.; Lauer, Fredine T.; Sun Xi; McDonald, Jacob D.; Hudson, Laurie G.; Liu Kejian

2009-01-01

In these studies the immunotoxicity of arsenic trioxide (ATO, As 2 O 3 ) was evaluated in mice following 14 days of inhalation exposures (nose only, 3 h per day) at concentrations of 50 μg/m 3 and 1 mg/m 3 . A biodistribution analysis performed immediately after inhalation exposures revealed highest levels of arsenic in the kidneys, bladder, liver, and lung. Spleen cell levels were comparable to those found in the blood, with the highest concentration of arsenic detected in the spleen being 150 μg/g tissue following the 1 mg/m 3 exposures. No spleen cell cytotoxicity was observed at either of the two exposure levels. There were no changes in spleen cell surface marker expression for B cells, T cells, macrophages, and natural killer (NK) cells. There were also no changes detected in the B cell (LPS-stimulated) and T cell (Con A-stimulated) proliferative responses of spleen cells, and no changes were found in the NK-mediated lysis of Yac-1 target cells. The primary T-dependent antibody response was, however, found to be highly susceptible to ATO suppression. Both the 50 μg/m 3 and 1 mg/m 3 exposures produced greater than 70% suppression of the humoral immune response to sheep red blood cells. Thus, the primary finding of this study is that the T-dependent humoral immune response is extremely sensitive to suppression by ATO and assessment of humoral immune responses should be considered in evaluating the health effects of arsenic containing agents.

Methyl group balance in brain and liver: role of choline on increased S-adenosyl methionine (SAM) demand by chronic arsenic exposure.

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Ríos, Rosalva; Santoyo, Martha E; Cruz, Daniela; Delgado, Juan Manuel; Zarazúa, Sergio; Jiménez-Capdeville, María E

2012-11-30

Arsenic toxicity has been related to its interference with one carbon metabolism, where a high demand of S-adenosylmethionine (SAM) for arsenic methylation as well as a failure of its regeneration would compromise the availability of methyl groups for diverse cellular functions. Since exposed animals show disturbances of methylated products such as methylated arginines, myelin and axon membranes, this work investigates whether alterations of SAM, choline and phosphatidylcholine (PC) in the brain of arsenic exposed rats are associated with myelin alterations and myelin basic protein (MBP) immunoreactivity. Also these metabolites, morphologic and biochemical markers of methyl group alterations were analyzed in the liver, the main site of arsenic methylation. In adult, life-long arsenic exposed rats through drinking water (3 ppm), no changes of SAM, choline and PC concentrations where found in the brain, but SAM and PC were severely decreased in liver accompanied by a significant increase of choline. These results suggest that choline plays an important role as methyl donor in arsenic exposure, which could underlie hepatic affections observed when arsenic exposure is combined with other environmental factors. Also, important myelin and nerve fiber alterations, accompanied by a 75% decrease of MBP immunoreactivity were not associated with a SAM deficit in the brain. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Estimating the risk of bladder and kidney cancer from exposure to low-levels of arsenic in drinking water, Nova Scotia, Canada.

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Saint-Jacques, Nathalie; Brown, Patrick; Nauta, Laura; Boxall, James; Parker, Louise; Dummer, Trevor J B

2018-01-01

Arsenic in drinking water impacts health. Highest levels of arsenic have been historically observed in Taiwan and Bangladesh but the contaminant has been affecting the health of people globally. Strong associations have been confirmed between exposure to high-levels of arsenic in drinking water and a wide range of diseases, including cancer. However, at lower levels of exposure, especially near the current World Health Organization regulatory limit (10μg/L), this association is inconsistent as the effects are mostly extrapolated from high exposure studies. This ecological study used Bayesian inference to model the relative risk of bladder and kidney cancer at these lower concentrations-0-2μg/L; 2-5μg/L and; ≥5μg/L of arsenic-in 864 bladder and 525 kidney cancers diagnosed in the study area, Nova Scotia, Canada between 1998 and 2010. The model included proxy measures of lifestyle (e.g. smoking) and accounted for spatial dependencies. Overall, bladder cancer risk was 16% (2-5μg/L) and 18% (≥5μg/L) greater than that of the referent group (water arsenic-levels within the current the World Health Organization maximum acceptable concentration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metabolomic profiles of arsenic (+3 oxidation state) methyltransferase knockout mice: Effect of sex and arsenic exposure

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Huang, Madelyn C.; Douillet, Christelle; Su, Mingming; Zhou, Kejun; Wu, Tao; Chen, Wenlian; Galanko, Joseph A.; Drobná, Zuzana; Saunders, R. Jesse; Martin, Elizabeth; Fry, Rebecca C.; Jia, Wei; Stýblo, Miroslav

2016-01-01

Arsenic (+3 oxidation state) methyltransferase (As3mt) is the key enzyme in the pathway for methylation of inorganic arsenic (iAs). Altered As3mt expression and AS3MT polymorphism have been linked to changes in iAs metabolism and in susceptibility to iAs toxicity in laboratory models and in humans. As3mt-knockout mice have been used to study the association between iAs metabolism and adverse effects of iAs exposure. However, little is known about systemic changes in metabolism of these mice and how these changes lead to their increased susceptibility to iAs toxicity. Here, we compared plasma and urinary metabolomes of male and female wild-type (WT) and As3mt-KO (KO) C57BL6 mice and examined metabolomic shifts associated with iAs exposure in drinking water. Surprisingly, exposure to 1 ppm As elicited only small changes in the metabolite profiles of either WT or KO mice. In contrast, comparisons of KO mice with WT mice revealed significant differences in plasma and urinary metabolites associated with lipid (phosphatidylcholines, cytidine, acyl-carnitine), amino acid (hippuric acid, acetylglycine, urea), and carbohydrate (L-sorbose, galactonic acid, gluconic acid) metabolism. Notably, most of these differences were sex-specific. Sex-specific differences were also found between WT and KO mice in plasma triglyceride and lipoprotein cholesterol levels. Some of the differentially changed metabolites (phosphatidylcholines, carnosine, and sarcosine) are substrates or products of reactions catalyzed by other methyltransferases. These results suggest that As3mt KO alters major metabolic pathways in a sex-specific manner, independent of iAs treatment, and that As3mt may be involved in other cellular processes beyond iAs methylation. PMID:26883664

Chronic exposure to arsenic, estrogen, and their combination causes increased growth and transformation in human prostate epithelial cells potentially by hypermethylation-mediated silencing of MLH1.

Science.gov (United States)

Treas, Justin; Tyagi, Tulika; Singh, Kamaleshwar P

2013-11-01

Chronic exposure to arsenic and estrogen is associated with risk of prostate cancer, but their mechanism is not fully understood. Additionally, the carcinogenic effects of their co-exposure are not known. Therefore, the objective of this study was to evaluate the effects of chronic exposure to arsenic, estrogen, and their combination, on cell growth and transformation, and identify the mechanism behind these effects. RWPE-1 human prostate epithelial cells were chronically exposed to arsenic and estrogen alone and in combination. Cell growth was measured by cell count and cell cycle, whereas cell transformation was evaluated by colony formation assay. Gene expression was measured by quantitative real-time PCR and confirmed at protein level by Western blot analysis. MLH1 promoter methylation was determined by pyrosequencing method. Exposure to arsenic, estrogen, and their combinations increases cell growth and transformation in RWPE-1 cells. Increased expression of Cyclin D1 and Bcl2, whereas decreased expression of mismatch repair genes MSH4, MSH6, and MLH1 was also observed. Hypermethylation of MLH1 promoter further suggested the epigenetic inactivation of MLH1 expression in arsenic and estrogen treated cells. Arsenic and estrogen combination caused greater changes than their individual treatments. Findings of this study for the first time suggest that arsenic and estrogen exposures cause increased cell growth and survival potentially through epigenetic inactivation of MLH1 resulting in decreased MLH1-mediated apoptotic response, and consequently increased cellular transformation. © 2013 Wiley Periodicals, Inc.

Urinary arsenic species, toenail arsenic, and arsenic intake estimates in a Michigan population with low levels of arsenic in drinking water.

Science.gov (United States)

Rivera-Núñez, Zorimar; Meliker, Jaymie R; Meeker, John D; Slotnick, Melissa J; Nriagu, Jerome O

2012-01-01

The large disparity between arsenic concentrations in drinking water and urine remains unexplained. This study aims to evaluate predictors of urinary arsenic in a population exposed to low concentrations (≤50 μg/l) of arsenic in drinking water. Urine and drinking water samples were collected from a subsample (n=343) of a population enrolled in a bladder cancer case-control study in southeastern Michigan. Total arsenic in water and arsenic species in urine were determined using ICP-MS: arsenobetaine (AsB), arsenite (As[III]), arsenate (As[V]), methylarsenic acid (MMA[V]), and dimethylarsenic acid (DMA[V]). The sum of As[III], As[V], MMA[V], and DMA[V] was denoted as SumAs. Dietary information was obtained through a self-reported food intake questionnaire. Log(10)-transformed drinking water arsenic concentration at home was a significant (Pwater were removed and further improved when analyses were applied to individuals who consumed amounts of home drinking water above the median volume (R(2)=0.40, Pwater was 0.42. Results show that arsenic exposure from drinking water consumption is an important determinant of urinary arsenic concentrations, even in a population exposed to relatively low levels of arsenic in drinking water, and suggest that seafood intake may influence urinary DMA[V] concentrations.

Arsenic and cadmium exposure in children living near a smelter complex in San Luis Potosi, Mexico

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Diaz-Barriga, F.; Santos, M.A.; Mejia, J.J.; Batres, L.; Yanez, L.; Carrizales, L.; Vera, E.; del Razo, L.M.; Cebrian, M.E. (Universidad Autonoma de San Luis Potosi (Mexico))

1993-08-01

The main purpose of this study was to assess environmental contamination by arsenic and cadmium in a smelter community (San Luis Potosi City, Mexico) and its possible contribution to an increased body burden of these elements in children. Arsenic and cadmium were found in the environment (air, soil, and household dust, and tap water) as well as in the urine and hair from children. The study was undertaken in three zones: Morales, an urban area close to the smelter complex; Graciano, an urban area 7 km away from the complex; and Mexquitic, a small rural town 25 km away. The environmental study showed that Morales is the most contaminated of the zones studied. The range of arsenic levels in soil (117-1396 ppm), dust (515-2625 ppm), and air (0.13-1.45 micrograms/m3) in the exposed area (Morales) was higher than those in the control areas. Cadmium concentrations were also higher in Morales. Estimates of the arsenic ingestion rate in Morales (1.0-19.8 micrograms/kg/day) were equal to or higher than the reference dose of 1 microgram/kg/day calculated by the Environmental Protection Agency. The range of arsenic levels in urine (69-594 micrograms/g creatinine) and hair (1.4-57.3 micrograms/g) and that of cadmium in hair (0.25-3.5 micrograms/g) indicated that environmental exposure has resulted in an increased body burden of these elements in children, suggesting that children living in Morales are at high risk of suffering adverse health effects if exposure continues.

Acute, but not Chronic, Exposure to Arsenic Provokes Glucose Intolerance in Rats: Possible Roles for Oxidative Stress and the Adrenergic Pathway.

Science.gov (United States)

Rezaei, Mohsen; Khodayar, Mohammd Javad; Seydi, Enayatollah; Soheila, Alboghobeish; Parsi, Isa Kazemzadeh

2017-06-01

Health problems due to heavy metals have become a worldwide concern. Along with its carcinogenicity, arsenic exposure results in impairment of glucose metabolism and insulin secretion as well as altered gene expression and signal transduction. However, the exact mechanism behind the behaviour of arsenic on glucose homeostasis and insulin secretion has not yet been fully understood. Fasting blood sugar and glucose tolerance tests were evaluated. In this study, we demonstrated that arsenic, when acutely administered, induced glucose intolerance in rats, although its chronic oral exposure did not provoke any glucose intolerance or hyperglycemia in rats. The protective activity of N-acetylcysteine, carvedilol and propranolol in male rats exposed to arsenic were also assessed, and N-acetylcysteine, particularly at 40 and 80 mg/kg, prevented the glucose intolerance induced in rats by arsenic. The present study showed that acute, but not chronic, contact with arsenic generates significant changes in the normal glucose tolerance pattern that may be due fundamentally to overproduction of reactive oxygen species and oxidative stress and is preventable by using N-acetylcysteine, a thiol-containing antioxidant. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Association Between Variants in Arsenic (+3 Oxidation State) Methyltranserase (AS3MT) and Urinary Metabolites of Inorganic Arsenic: Role of Exposure Level

Science.gov (United States)

Xu, Xiaofan; Drobná, Zuzana; Voruganti, V. Saroja; Barron, Keri; González-Horta, Carmen; Sánchez-Ramírez, Blanca; Ballinas-Casarrubias, Lourdes; Cerón, Roberto Hernández; Morales, Damián Viniegra; Terrazas, Francisco A. Baeza; Ishida, María C.; Gutiérrez-Torres, Daniela S.; Saunders, R. Jesse; Crandell, Jamie; Fry, Rebecca C.; Loomis, Dana; García-Vargas, Gonzalo G.; Del Razo, Luz M.; Stýblo, Miroslav; Mendez, Michelle A.

2016-01-01

Abstract Variants in AS3MT, the gene encoding arsenic (+3 oxidation state) methyltranserase, have been shown to influence patterns of inorganic arsenic (iAs) metabolism. Several studies have suggested that capacity to metabolize iAs may vary depending on levels of iAs exposure. However, it is not known whether the influence of variants in AS3MT on iAs metabolism also vary by level of exposure. We investigated, in a population of Mexican adults exposed to drinking water As, whether associations between 7 candidate variants in AS3MT and urinary iAs metabolites were consistent with prior studies, and whether these associations varied depending on the level of exposure. Overall, associations between urinary iAs metabolites and AS3MT variants were consistent with the literature. Referent genotypes, defined as the genotype previously associated with a higher percentage of urinary dimethylated As (DMAs%), were associated with significant increases in the DMAs% and ratio of DMAs to monomethylated As (MAs), and significant reductions in MAs% and iAs%. For 3 variants, associations between genotypes and iAs metabolism were significantly stronger among subjects exposed to water As >50 versus ≤50 ppb (water As X genotype interaction P iAs exposure may influence the extent to which several AS3MT variants affect iAs metabolism. The variants most strongly associated with iAs metabolism—and perhaps with susceptibility to iAs-associated disease—may vary in settings with exposure level. PMID:27370415

Association between arsenic exposure from a coal-burning power plant and urinary arsenic concentrations in Prievidza District, Slovakia

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Ranft, U.; Miskovic, P.; Pesch, B.; Jakubis, P.; Fabianova, E.; Keegan, T.; Hergemoller, A.; Jakubis, M.; Nieuwenhuijsen, M.J. [University of Dusseldorf, Dusseldorf (Germany)

2003-06-01

To assess the arsenic exposure of a population living in the vicinity of a coal-burning power plant with high arsenic emission in the Prievidza District, Slovakia, 548 spot urine samples were speciated for inorganic As (As-inorg), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and their sum (As-sum). The urine samples were collected from the population of a case-control study on nonmelanoma skin cancer (NMSC). A total of 411 samples with complete As speciations and sufficient urine quality and without fish consumption were used for statistical analysis. Although current environmental As exposure and urinary As concentrations were low (median As in soil within 5 km distance to the power plant, 41 {mu}g/g; median urinary As-sum, 5.8 {mu}g/L), there was a significant but weak association between As in soil and urinary As-sum (r = 0.21, p {lt} 0.01). We performed a multivariate regression analysis to calculate adjusted regression coefficients for environmental As exposure and other determinants of urinary As. Persons living in the vicinity of the plant had 27% higher As-sum values (p {lt} 0.01), based on elevated concentrations of the methylated species. A 32% increase of MMA occurred among subjects who consumed homegrown food (p {lt} 0.001). NMSC cases had significantly higher levels of As-sum, DMA, and As-inorg. The methylation index As-inorg/(MMA + DMA) was about 20% lower among cases (p {lt} 0.05) and in men (p {lt} 0.05) compared with controls and females, respectively.

Arsenic speciation in hair and nails of acute promyelocytic leukemia (APL) patients undergoing arsenic trioxide treatment.

Science.gov (United States)

Chen, Baowei; Cao, Fenglin; Lu, Xiufen; Shen, Shengwen; Zhou, Jin; Le, X Chris

2018-07-01

Arsenic in hair and nails has been used to assess chronic exposure of humans to environmental arsenic. However, it remains to be seen whether it is appropriate to evaluate acute exposure to sub-lethal doses of arsenic typically used in therapeutics. In this study, hair, fingernail and toenail samples were collected from nine acute promyelocytic leukemia (APL) patients who were administered intravenously the daily dose of 10 mg arsenic trioxide (7.5 mg arsenic) for up to 54 days. These hair and nail samples were analyzed for arsenic species using high performance liquid chromatography separation and inductively coupled plasma mass spectrometry detection (HPLC-ICPMS). Inorganic arsenite was the predominant form among water-extractable arsenicals. Dimethylarsinic acid (DMA V ), monomethylarsonic acid (MMA V ), monomethylarsonous acid (MMA III ), monomethylmonothioarsonic acid (MMMTA V ), and dimethylmonothioarsinic acid (DMMTA V ) were also detected in both hair and nail samples. This is the first report of the detection of MMA III and MMMTA V as metabolites of arsenic in hair and nails of APL patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Arsenic exacerbates atherosclerotic lesion formation and inflammation in ApoE-/- mice

International Nuclear Information System (INIS)

Srivastava, Sanjay; Vladykovskaya, Elena N.; Haberzettl, Petra; Sithu, Srinivas D.; D'Souza, Stanley E.; States, J. Christopher

2009-01-01

Exposure to arsenic-contaminated water has been shown to be associated with cardiovascular disease, especially atherosclerosis. We examined the effect of arsenic exposure on atherosclerotic lesion formation, lesion composition and nature in ApoE-/- mice. Early post-natal exposure (3-week-old mice exposed to 49 ppm arsenic as NaAsO 2 in drinking water for 7 weeks) increased the atherosclerotic lesion formation by 3- to 5-fold in the aortic valve and the aortic arch, without affecting plasma cholesterol. Exposure to arsenic for 13 weeks (3-week-old mice exposed to 1, 4.9 and 49 ppm arsenic as NaAsO 2 in drinking water) increased the lesion formation and macrophage accumulation in a dose-dependent manner. Temporal studies showed that continuous arsenic exposure significantly exacerbated the lesion formation throughout the aortic tree at 16 and 36 weeks of age. Withdrawal of arsenic for 12 weeks after an initial exposure for 21 weeks (to 3-week-old mice) significantly decreased lesion formation as compared with mice continuously exposed to arsenic. Similarly, adult exposure to 49 ppm arsenic for 24 weeks, starting at 12 weeks of age increased lesion formation by 2- to 3.6-fold in the aortic valve, the aortic arch and the abdominal aorta. Lesions of arsenic-exposed mice displayed a 1.8-fold increase in macrophage accumulation whereas smooth muscle cell and T-lymphocyte contents were not changed. Expression of pro-inflammatory chemokine MCP-1 and cytokine IL-6 and markers of oxidative stress, protein-HNE and protein-MDA adducts were markedly increased in lesions of arsenic-exposed mice. Plasma concentrations of MCP-1, IL-6 and MDA were also significantly elevated in arsenic-exposed mice. These data suggest that arsenic exposure increases oxidative stress, inflammation and atherosclerotic lesion formation.

MiADMSA reverses impaired mitochondrial energy metabolism and neuronal apoptotic cell death after arsenic exposure in rats

Energy Technology Data Exchange (ETDEWEB)

Dwivedi, Nidhi; Mehta, Ashish; Yadav, Abhishek [Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior-474 002 (India); Binukumar, B.K.; Gill, Kiran Dip [Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh-160 012 (India); Flora, Swaran J.S., E-mail: sjsflora@hotmail.com [Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior-474 002 (India)

2011-11-15

Arsenicosis, due to contaminated drinking water, is a serious health hazard in terms of morbidity and mortality. Arsenic induced free radicals generated are known to cause cellular apoptosis through mitochondrial driven pathway. In the present study, we investigated the effect of arsenic interactions with various complexes of the electron transport chain and attempted to evaluate if there was any complex preference of arsenic that could trigger apoptosis. We also evaluated if chelation with monoisoamyl dimercaptosuccinic acid (MiADMSA) could reverse these detrimental effects. Our results indicate that arsenic exposure induced free radical generation in rat neuronal cells, which diminished mitochondrial potential and enzyme activities of all the complexes of the electron transport chain. Moreover, these complexes showed differential responses towards arsenic. These early events along with diminished ATP levels could be co-related with the later events of cytosolic migration of cytochrome c, altered bax/bcl{sub 2} ratio, and increased caspase 3 activity. Although MiADMSA could reverse most of these arsenic-induced altered variables to various extents, DNA damage remained unaffected. Our study for the first time demonstrates the differential effect of arsenic on the complexes leading to deficits in bioenergetics leading to apoptosis in rat brain. However, more in depth studies are warranted for better understanding of arsenic interactions with the mitochondria. -- Research highlights: Black-Right-Pointing-Pointer Arsenic impairs mitochondrial energy metabolism leading to neuronal apoptosis. Black-Right-Pointing-Pointer Arsenic differentially affects mitochondrial complexes, I - III and IV being more sensitive than complex II. Black-Right-Pointing-Pointer Arsenic-induced apoptosis initiates through ROS generation or impaired [Ca{sup 2+}]i homeostasis. Black-Right-Pointing-Pointer MiADMSA reverses arsenic toxicity via intracellular arsenic- chelation, antioxidant

Late effects of iodine-131 in utero exposure: Toxicological effects in first generation of rats

International Nuclear Information System (INIS)

Liu, P.T.; Stevens, R.H.; Cole, D.A.; Lindholm, P.A.; Cheng, H.F.

1984-01-01

The authors have initiated studies to evaluate the possible immunotoxic effects to both the mother and offspring following an in utero exposure to /sup 131/I, and initial observations suggest induction of antitumor immunity as measured by cell-mediated immune (CMI) and antibody-dependent cell-mediated cytotoxicity (ADCC). The animal model selected for these studies was the Fischer F344 female rat intraperitoneally exposed to concentrations ranging from 4 to 3700 kBq of Na/sup 131/I during the gestation period of 16 to 18 days. The CMI results suggested the male offspring were 1.7 times more immunologically responsive than their sisters with a threshold detection level in the range of 9.25 kBq being observed. The parents of F/sub 1/ generation exposed to the /sup 131/I are now being evaluated for possible immunotoxicity according to: host resistance to E. coli endotoxin and blastogenenic responses to phytohemagglutin, concanavalin A, and lipopolysaccharide. The results of these studies suggest that perinatal /sup 131/I exposure exerts an immunotoxic effect upon the first generation

Effects of in utero tributyltin chloride exposure in the rat on pregnancy outcome.

Science.gov (United States)

Adeeko, Adedayo; Li, Daming; Forsyth, Don S; Casey, Valerie; Cooke, Gerard M; Barthelemy, Johanna; Cyr, Daniel G; Trasler, Jacquetta M; Robaire, Bernard; Hales, Barbara F

2003-08-01

Tributyltin, an organotin, is ubiquitous in the environment. The consumption of contaminated marine species leads to human dietary exposure to this compound. Tributyltin is an endocrine disruptor in many wildlife species and inhibits aromatase in mammalian placental and granulosa-like tumor cell lines. We investigated the effects of tributyltin chloride exposure on pregnancy outcome in the Sprague-Dawley rat. Timed pregnant rats were gavaged either with vehicle (olive oil) or tributyltin chloride (0.25, 2.5, 10, or 20 mg/kg) from days 0-19 or 8-19 of gestation. On gestational day 20, dams were sacrificed, and pregnancy outcome was determined. Tributyltin and its metabolites (dibutyltin, monobutyltin) were measured in maternal blood by gas chromatography. Both tributyltin and dibutyltin were present in maternal blood at approximately equal concentrations, whereas monobutyltin contributed minimally to total organotins. Organotin concentrations increased in a dose-dependent pattern in dams, independent of the window of exposure. Tributyltin chloride administration significantly reduced maternal weight gain only at the highest dose (20 mg/kg); a significant increase in post-implantation loss and decreased litter sizes, in addition to decreased fetal weights, was observed in this group. Tributyltin chloride exposure did not result in external malformations, nor was there a change in sex ratios. However, exposure to 0.25, 2.5, or 10 mg/kg tributyltin chloride from gestation days (GD) 0-19 resulted in a significant increase in normalized anogenital distances in male fetuses; exposure from days 8-19 had no effect. There was a dramatic increase in the incidence of low weight (exposure to 20 mg/kg tributyltin chloride. Delayed ossification of the fetal skeleton was observed after in utero exposure to either 10 mg/kg or 20 mg/kg tributyltin chloride. Serum thyroxine and triiodothyronine levels were reduced significantly in dams exposed to 10 and 20 mg/kg tributyltin chloride

Arsenic (As Contamination in Different Food and Dietary Samples from Several Districts of Bangladesh and Arsenic (As Detection, Mitigation and Toxicity Measurement and impact of Dietary Arsenic Exposure on Human Health

Directory of Open Access Journals (Sweden)

M A Awal

2010-10-01

Full Text Available Objective: To determine the level of arsenic concentration in vegetables and other food categories in three selected areas of Pabna district and to estimate quantitatively the dietary arsenic exposure in one of the arsenic contaminated areas of Bangladesh.Materials and Methods: The study was conducted in CharRuppur, Char mirkamari and Lakshmikunda village of IshwardiUpzila in Pabna district. Ishwardi (Town consists of 12 wardsand 37 mahallas. Arsenic was detected in the ADM Lab,Department of Pharmacology, Bangladesh Agricultural University, Mymensingh with Hydride Generation Atomic Absorption Spectrophotometer (HG-AAS; PG-990, PG Instruments Ltd. UK. Arsenic was detected by forming AsH3 at below pH 1.0 after the reaction of As with a solution of sodiumborohydride (NaBH4, sodium hydroxide (NaOH, M=40,000g/mol, and 10% HCl. In this test, standard was maintained asAsV ranging from 0 to 12.5 μg/L.Results: A total of 120 vegetable samples, 15 rice samples and15 fish samples were collected from five different markets ofthree different villages of Pabna district and were tested forarsenic concentration. Findings demonstrated that the mean concentration of As in leafy vegetables (0.52 μg g-1 was significantly higher compared to those found in fruity (0.422μg g-1 and root & tuber vegetables (0.486 μg g-1.Conclusion: Underground Contaminated water was the major source for the As contamination of various products in Pabna.The arsenic levels were found higher among the leafy vegetables samples in comparison to fruit and root & tuber vegetables. Further studies will be conducted to search the genetic risk factors of arsenic toxicity in the population of the mostly affected people.

Relationship between arsenic skin lesions and the age of natural menopause.

Science.gov (United States)

Yunus, Fakir Md; Rahman, Musarrat Jabeen; Alam, Md Zahidul; Hore, Samar Kumar; Rahman, Mahfuzar

2014-05-02

Chronic exposure to arsenic is associated with neoplastic, cardiovascular, endocrine, neuro-developmental disorders and can have an adverse effect on women's reproductive health outcomes. This study examined the relationship between arsenic skin lesions (a hallmark sign of chronic arsenic poisoning) and age of natural menopause (final menopausal period) in populations with high levels of arsenic exposure in Bangladesh. We compared menopausal age in two groups of women--with and without arsenic skin lesions; and presence of arsenic skin lesions was used as an indicator for chronic arsenic exposure. In a cross-sectional study, a total of 210 participants were randomly identified from two ongoing studies--participants with arsenic skin lesions were identified from an ongoing clinical trial and participants with no arsenic skin lesions were identified from an ongoing cohort study. Mean age of menopause between these two groups were calculated and compared. Multivariable linear regression was used to estimate the relationship between the status of the arsenic skin lesions and age of natural menopause in women. Women with arsenic skin lesions were 1.5 years younger (p <0.001) at the time of menopause compared to those without arsenic skin lesions. After adjusting with contraceptive use, body mass index, urinary arsenic level and family history of premature menopause, the difference between the groups' age at menopause was 2.1 years earlier (p <0.001) for respondents with arsenic skin lesions. The study showed a statistically significant association between chronic exposure to arsenic and age at menopause. Heavily exposed women experienced menopause two years earlier than those with lower or no exposure.

Morbid condition involving cardio-vascular, broncho-pulmonary, digestive and neural lesions in children and young adults after dietary arsenic exposure

Energy Technology Data Exchange (ETDEWEB)

Zaldivar, R.

1980-02-01

An investigation on the relationship between dietary arsenic exposure and cardiovascular diseases was made. In Antofagasta Commune, northern Chile, since 1955 arsenic has polluted public drinking water. This environmental contamination is of geological origin. The concentration of arsenic in drinking water for the 1955 to 1970 period was 0.5980 ppM. In the period June 1970 to March 1972, the concentration decreased to 0.0815 ppM due to a water filtration plant which started operating in May 1970. Greater Santiago showed 0.00 ppM of arsenic in drinking water. Amongst 10 autopsied patients with chronic arsenical dermatosis from Antofagasta Commune, 9 showed marked fibrous intimal thickening of the arterial wall and/or restricted lumen of the left coronary artery, 2 of these 9 also exhibiting myocardial infarction. Of the 10 patients, 7 developed cardiomegaly, which was related to chronic exposure to dietary arsenic. Two series of patients with myocardial infarction under 40 years of age, one from Antofagasta Commune, the other from greater Santiago (not exposed to arsenic) were compared. The Yates corrected chi 2 value being 11.7776. The difference was statistically highly significant. In Antofagasta Commune, the number of cases which had myocardial infarction with chronic arsenical dermatosis were compared with the cases which showed, myocardial infarction without chronic arsenical dermatosis. The Yates corrected chi 2 value was 13.0395. A highly significant difference was detected. Children from the two cities were also compared. The number of cases with myocardial infarction showed a significant difference; Fisher's exact test yielded a P approximately equal to 0.004944, the Yates corrected chi 2 value being 20.7311. The number of children with systemic occlusive arterial disease from the two cities also exhibited a highly significant difference.

Analysis of the risk of disease associated with arsenic exposure in water supply systems for human consumption

International Nuclear Information System (INIS)

Villegas Gonzalez, Nicole

2014-01-01

The risk of disease associated with arsenic exposure is analyzed in water supply systems for human consumption, as well as the control of pollution and effects on health, in the community known as Barrio Hotel of Canas in comparison with the community of San Miguel in Canas, Guanacaste, Costa Rica. A spatial analysis, temporal and classification are realized by an ecological design of the country in the following zones of exposure: without exposure, low (≥3 μg/L and ≤10 μg/L) and medium to high (≥11 μg/L and ≤187 μg/L). The transversal design is tackled through the perceived morbidity. Spatial analysis has found in the districts of Bebedero, Los Chiles, Bagaces and Canas with Standardized Morbidity Index (EMI) by age in the the greatest national range of chronic renal failure (CRF). The protection of skin cancer risk is observed in the communities of Bagaces, Canas, El Amparo and La Cruz. A temporal trend of increase in IME of CRF and skin cancer is identified in Los Chiles. The classification by zone of exposure, the unexposed areas have been protected of kidney cancer, lung and bronchus, bladder and skin. The of low exposure have presented excess risk of CRF and have been protected of skin cancer. The of medium to high are protected of bladder cancer and have maintained the trend of excess in CRF and protection of skin cancer. The transversal design has found in the exposed community the risk to suffer kidneys diseases. Arsenic exposure has increased in men the risk of renal failure and anemia, in women the decrease of vision, and age groups under of 10 years and of 40-69 years of hypopigmentation and keratoses respectively. Multivariate analysis has showed a weak association of arsenic exposure time with the risk of hypertension [es

Circulatory responses to asphyxia differ if the asphyxia occurs in utero or ex utero in near-term lambs.

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Kristina S Sobotka

Full Text Available A cornerstone of neonatal resuscitation teaching suggests that a rapid vagal-mediated bradycardia is one of the first signs of perinatal compromise. As this understanding is based primarily on fetal studies, we investigated whether the heart rate and blood pressure response to total asphyxia is influenced by whether the animal is in utero or ex utero.Fetal sheep were instrumented at ∼ 139 days of gestation and then asphyxiated by umbilical cord occlusion until mean arterial blood pressure decreased to ∼ 20 mmHg. Lambs were either completely submerged in amniotic fluid (in utero; n = 8 throughout the asphyxia or were delivered and then remained ex utero (ex utero; n = 8 throughout the asphyxia. Heart rate and arterial blood pressure were continuously recorded.Heart rate was higher in ex utero lambs than in utero lambs. Heart rates in in utero lambs rapidly decreased, while heart rates in ex utero lambs initially increased following cord occlusion (for ∼ 1.5 min before they started to decrease. Mean arterial pressure initially increased then decreased in both groups.Heart rate response to asphyxia was markedly different depending upon whether the lamb was in utero or ex utero. This indicates that the cardiovascular responses to perinatal asphyxia are significantly influenced by the newborn's local environment. As such, based solely on heart rate, the stage and severity of a perinatal asphyxic event may not be as accurate as previously assumed.

Arsenic inhibits hedgehog signaling during P19 cell differentiation

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Liu, Jui Tung [Environmental Toxicology Program, Clemson University, 132 Long Hall, Clemson, SC 29634 (United States); Bain, Lisa J., E-mail: lbain@clemson.edu [Environmental Toxicology Program, Clemson University, 132 Long Hall, Clemson, SC 29634 (United States); Department of Biological Sciences, Clemson University, 132 Long Hall, Clemson, SC 29634 (United States)

2014-12-15

Arsenic is a toxicant found in ground water around the world, and human exposure mainly comes from drinking water or from crops grown in areas containing arsenic in soils or water. Epidemiological studies have shown that arsenic exposure during development decreased intellectual function, reduced birth weight, and altered locomotor activity, while in vitro studies have shown that arsenite decreased muscle and neuronal cell differentiation. The sonic hedgehog (Shh) signaling pathway plays an important role during the differentiation of both neurons and skeletal muscle. The purpose of this study was to investigate whether arsenic can disrupt Shh signaling in P19 mouse embryonic stem cells, leading to changes muscle and neuronal cell differentiation. P19 embryonic stem cells were exposed to 0, 0.25, or 0.5 μM of sodium arsenite for up to 9 days during cell differentiation. We found that arsenite exposure significantly reduced transcript levels of genes in the Shh pathway in both a time and dose-dependent manner. This included the Shh ligand, which was decreased 2- to 3-fold, the Gli2 transcription factor, which was decreased 2- to 3-fold, and its downstream target gene Ascl1, which was decreased 5-fold. GLI2 protein levels and transcriptional activity were also reduced. However, arsenic did not alter GLI2 primary cilium accumulation or nuclear translocation. Moreover, additional extracellular SHH rescued the inhibitory effects of arsenic on cellular differentiation due to an increase in GLI binding activity. Taken together, we conclude that arsenic exposure affected Shh signaling, ultimately decreasing the expression of the Gli2 transcription factor. These results suggest a mechanism by which arsenic disrupts cell differentiation. - Highlights: • Arsenic exposure decreases sonic hedgehog pathway-related gene expression. • Arsenic decreases GLI2 protein levels and transcriptional activity in P19 cells. • Arsenic exposure does not alter the levels of SHH

Probabilistic Risk Assessment of Cancer from Exposure Inorganic Arsenic in Duplicate Food by Villagers in Ronphibun, Thailand

OpenAIRE

Piyawat Saipan

2010-01-01

Ronphibun district is a district in Nakorn Si Thammarat province, within southern Thailand. This district is the site of several former tin mines that were in operation 100 years ago. Arsenic contamination caused by past mining activities remains in the area. The specific purpose of this study was conducted to assess cancer risk in people living within Ronphibun district from exposure to inorganic arsenic via duplicate food using probabilistic risk assessment. A hundred and fifty duplicate fo...

Arsenic Speciation in US Consumed Rice with an Emphasis on Bioaccessiblity and the Exposure Assessment Implications Dataset

Data.gov (United States)

U.S. Environmental Protection Agency — Arsenic Speciation in US Consumed Rice with an Emphasis on Bioaccessiblity and the Exposure Assessment Implications. This dataset is associated with the following...

Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis.

Science.gov (United States)

Perry, Meghan R; Wyllie, Susan; Raab, Andrea; Feldmann, Joerg; Fairlamb, Alan H

2013-12-03

The Indian subcontinent is the only region where arsenic contamination of drinking water coexists with widespread resistance to antimonial drugs that are used to treat the parasitic disease visceral leishmaniasis. We have previously proposed that selection for parasite resistance within visceral leishmaniasis patients who have been exposed to trivalent arsenic results in cross-resistance to the related metalloid antimony, present in the pentavalent state as a complex in drugs such as sodium stibogluconate (Pentostam) and meglumine antimonate (Glucantime). To test this hypothesis, Leishmania donovani was serially passaged in mice exposed to arsenic in drinking water at environmentally relevant levels (10 or 100 ppm). Arsenic accumulation in organs and other tissues was proportional to the level of exposure and similar to that previously reported in human liver biopsies. After five monthly passages in mice exposed to arsenic, isolated parasites were found to be completely refractory to 500 μg · mL(-1) Pentostam compared with the control passage group (38.5 μg · mL(-1)) cultured in vitro in mouse peritoneal macrophages. Reassessment of resistant parasites following further passage for 4 mo in mice without arsenic exposure showed that resistance was stable. Treatment of infected mice with Pentostam confirmed that resistance observed in vitro also occurred in vivo. We conclude that arsenic contamination may have played a significant role in the development of Leishmania antimonial resistance in Bihar because inadequate treatment with antimonial drugs is not exclusive to India, whereas widespread antimonial resistance is.

History of Arsenic as a Poison and Medicinal

Science.gov (United States)

Since ancient times, human exposure to the metalloid arsenic has been both intentional and unintentional. The intentional exposure to arsenic has been to inflict harm on others as well as to be a curative agent for those who are ill. The unintentional exposure has either been f...

Effects of In Utero Thyroxine Exposure on Murine Cranial Suture Growth.

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R Nicole Howie

Full Text Available Large scale surveillance studies, case studies, as well as cohort studies have identified the influence of thyroid hormones on calvarial growth and development. Surveillance data suggests maternal thyroid disorders (hyperthyroidism, hypothyroidism with pharmacological replacement, and Maternal Graves Disease are linked to as much as a 2.5 fold increased risk for craniosynostosis. Craniosynostosis is the premature fusion of one or more calvarial growth sites (sutures prior to the completion of brain expansion. Thyroid hormones maintain proper bone mineral densities by interacting with growth hormone and aiding in the regulation of insulin like growth factors (IGFs. Disruption of this hormonal control of bone physiology may lead to altered bone dynamics thereby increasing the risk for craniosynostosis. In order to elucidate the effect of exogenous thyroxine exposure on cranial suture growth and morphology, wild type C57BL6 mouse litters were exposed to thyroxine in utero (control = no treatment; low ~167 ng per day; high ~667 ng per day. Thyroxine exposed mice demonstrated craniofacial dysmorphology (brachycranic. High dose exposed mice showed diminished area of the coronal and widening of the sagittal sutures indicative of premature fusion and compensatory growth. Presence of thyroid receptors was confirmed for the murine cranial suture and markers of proliferation and osteogenesis were increased in sutures from exposed mice. Increased Htra1 and Igf1 gene expression were found in sutures from high dose exposed individuals. Pathways related to the HTRA1/IGF axis, specifically Akt and Wnt, demonstrated evidence of increased activity. Overall our data suggest that maternal exogenous thyroxine exposure can drive calvarial growth alterations and altered suture morphology.

Effects of In Utero Thyroxine Exposure on Murine Cranial Suture Growth.

Science.gov (United States)

Howie, R Nicole; Durham, Emily L; Black, Laurel; Bennfors, Grace; Parsons, Trish E; Elsalanty, Mohammed E; Yu, Jack C; Weinberg, Seth M; Cray, James J

2016-01-01

Large scale surveillance studies, case studies, as well as cohort studies have identified the influence of thyroid hormones on calvarial growth and development. Surveillance data suggests maternal thyroid disorders (hyperthyroidism, hypothyroidism with pharmacological replacement, and Maternal Graves Disease) are linked to as much as a 2.5 fold increased risk for craniosynostosis. Craniosynostosis is the premature fusion of one or more calvarial growth sites (sutures) prior to the completion of brain expansion. Thyroid hormones maintain proper bone mineral densities by interacting with growth hormone and aiding in the regulation of insulin like growth factors (IGFs). Disruption of this hormonal control of bone physiology may lead to altered bone dynamics thereby increasing the risk for craniosynostosis. In order to elucidate the effect of exogenous thyroxine exposure on cranial suture growth and morphology, wild type C57BL6 mouse litters were exposed to thyroxine in utero (control = no treatment; low ~167 ng per day; high ~667 ng per day). Thyroxine exposed mice demonstrated craniofacial dysmorphology (brachycranic). High dose exposed mice showed diminished area of the coronal and widening of the sagittal sutures indicative of premature fusion and compensatory growth. Presence of thyroid receptors was confirmed for the murine cranial suture and markers of proliferation and osteogenesis were increased in sutures from exposed mice. Increased Htra1 and Igf1 gene expression were found in sutures from high dose exposed individuals. Pathways related to the HTRA1/IGF axis, specifically Akt and Wnt, demonstrated evidence of increased activity. Overall our data suggest that maternal exogenous thyroxine exposure can drive calvarial growth alterations and altered suture morphology.

Mouse arsenic (+3 oxidation state) methyltransferase genotype affects metabolism and tissue dosimetry of arsenicals after arsenite administration in drinking water.

Science.gov (United States)

Chen, Baowei; Arnold, Lora L; Cohen, Samuel M; Thomas, David J; Le, X Chris

2011-12-01

Arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes methylation of inorganic arsenic (iAs) producing a number of methylated arsenic metabolites. Although methylation has been commonly considered a pathway for detoxification of arsenic, some highly reactive methylated arsenicals may contribute to toxicity associated with exposure to inorganic arsenic. Here, adult female wild-type (WT) C57BL/6 mice and female As3mt knockout (KO) mice received drinking water that contained 1, 10, or 25 ppm (mg/l) of arsenite for 33 days and blood, liver, kidney, and lung were taken for arsenic speciation. Genotype markedly affected concentrations of arsenicals in tissues. Summed concentrations of arsenicals in plasma were higher in WT than in KO mice; in red blood cells, summed concentrations of arsenicals were higher in KO than in WT mice. In liver, kidney, and lung, summed concentrations of arsenicals were greater in KO than in WT mice. Although capacity for arsenic methylation is much reduced in KO mice, some mono-, di-, and tri-methylated arsenicals were found in tissues of KO mice, likely reflecting the activity of other tissue methyltransferases or preabsorptive metabolism by the microbiota of the gastrointestinal tract. These results show that the genotype for arsenic methylation determines the phenotypes of arsenic retention and distribution and affects the dose- and organ-dependent toxicity associated with exposure to inorganic arsenic.

Arsenic exposure and adverse health effects: A review of recent findings from arsenic and health studies in Matlab, Bangladesh

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Mohammad Yunus

2011-09-01

Full Text Available The recent discovery of large-scale arsenic (As contamination of groundwater has raised much concern in Bangladesh. Reliable estimates of the magnitude of As exposure and related health problems have not been comprehensively investigated in Bangladesh. A large population-based study on As and health consequences in Matlab (AsMat was done in Matlab field site where International Centre for Diarrhoeal Disease Research, Bangladesh has maintained a health and demographic surveillance system registering prospectively all vital events. Taking advantage of the health and demographic surveillance system and collecting data on detailed individual level As exposure using water and urine samples, AsMat investigated the morbidity and mortality associated with As exposure. Reviews of findings to date suggest the adverse effects of As exposure on the risk of skin lesions, high blood pressure, diabetes mellitus, chronic disease, and all-cause infant and adult disease mortality. Future studies of clinical endpoints will enhance our knowledge gaps and will give directions for disease prevention and mitigations.

Toxicological effects of arsenic exposure in a freshwater teleost fish ...

African Journals Online (AJOL)

High concentration of arsenic in groundwater in the north-eastern states of India has become a major cause of concern. Inorganic arsenic of geological origin is found in groundwater used as drinking-water in several parts of the world. Arsenic is used in various industries and agriculture and excessive arsenic finds its way ...

Evaluation of a subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonic acid oil derived from Mortierella alpina in rats

NARCIS (Netherlands)

Hempenius, R.A.; Lina, B.A.R.; Haggitt, R.C.

2000-01-01

Arachidonic acid oil (ARA-oil) derived from the fungus Mortierella alpina for use in infant nutrition was tested in a subchronic (13-week) oral toxicity study in rats, preceded by an in utero exposure phase. The ARA-oil was administered as admixture to the rodent diet at dose levels of 3000 ppm,

The polymorphisms of P53 codon 72 and MDM2 SNP309 and renal cell carcinoma risk in a low arsenic exposure area

Energy Technology Data Exchange (ETDEWEB)

Huang, Chao-Yuan [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Su, Chien-Tien [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Chu, Jan-Show [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Huang, Shu-Pin [Department of Urology, Kaohsiung Medical University Hospital, College of Medicine Kaohsiung Medical University, Kaohsiung, Taiwan (China); Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Yang, Hsiu-Yuan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Chung, Chi-Jung [Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Department of Health Risk Management, College of Public Health, China Medical University, Taichung, Taiwan (China); Wu, Chia-Chang [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, Taipei Medical Universtiy-Shuang Ho Hospital, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

2011-12-15

Our recent study demonstrated the increased risk of renal cell carcinoma (RCC) associated with high urinary total arsenic levels among people living in a low arsenic exposure area. Genomic instability is important in arsenic carcinogenesis. This study evaluated the relationship between the polymorphisms of p53, p21, and MDM2, which plays a role in gene stability, and the arsenic-related RCC risk. Here, we found that p53 Pro/Pro genotype and MDM2 SNP309 GG genotype significantly increased RCC risk compared to the p53 Arg/Arg genotype and MDM2 SNP309 TT genotype. RCC patients with the p53Arg/Arg genotype had a signicantly low percentage of inorganic arsenic, a low percentage of monomethylarsonic acid (MMA), and a high percentage of dimethylarsinic acid (DMA), which indicates efcient arsenic methylation capacity. Subjects with the p53 Arg/Pro + Pro/Pro genotype or MDM2 SNP309 TG + GG genotype, in conjunction with high urinary total arsenic ({>=} 14.02 {mu}g/L), had a signicantly higher RCC risk than those with the p53 Arg/Arg or MDM2 SNP309 TT genotypes and low urinary total arsenic. Taken together, this is the first study to show that a variant genotype of p53 Arg{sup 72}Pro or MDM2 SNP309 may modify the arsenic-related RCC risk even in a non-obvious arsenic exposure area. -- Highlights: Black-Right-Pointing-Pointer Subjects with p53 Pro/Pro or MDM2 GG genotype significantly increased RCC risk. Black-Right-Pointing-Pointer A significant multiplicative joint effect of p53 and p21 on RCC risk. Black-Right-Pointing-Pointer RCC patients with p53 Arg/Arg genotype had efficient arsenic methylation capacity. Black-Right-Pointing-Pointer Joint effect of p53 or MDM2 genotype and high urinary total arsenic on RCC risk.

Low doses of arsenic, via perturbing p53, promotes tumorigenesis

Energy Technology Data Exchange (ETDEWEB)

Ganapathy, Suthakar, E-mail: s.ganapathy@neu.edu [Center for Drug Development, Northeastern University, Boston (United States); Li, Ping [The First Affiliated Hospital, Zhengzhou University, Zhengzhou (China); The Institute of Clinic Sciences, Sahlgrenska Academy, Gothenburg (Sweden); Fagman, Johan [The Institute of Clinic Sciences, Sahlgrenska Academy, Gothenburg (Sweden); Yu, Tianqi; Lafontant, Jean [Center for Drug Development, Northeastern University, Boston (United States); Zhang, Guojun [The First Affiliated Hospital, Zhengzhou University, Zhengzhou (China); Chen, Changyan [Center for Drug Development, Northeastern University, Boston (United States); The Institute of Clinic Sciences, Sahlgrenska Academy, Gothenburg (Sweden)

2016-09-01

In drinking water and in workplace or living environments, low doses of arsenic can exist and operate as a potent carcinogen. Due to insufficient understanding and information on the pervasiveness of environmental exposures to arsenic, there is an urgent need to elucidate the underlying molecular mechanisms of arsenic regarding its carcinogenic effect on human health. In this study, we demonstrate that low doses of arsenic exposure mitigate or mask p53 function and further perturb intracellular redox state, which triggers persistent endoplasmic reticulum (ER) stress and activates UPR (unfolded protein response), leading to transformation or tumorigenesis. Thus, the results suggest that low doses of arsenic exposure, through attenuating p53-regulated tumor suppressive function, change the state of intracellular redox and create a microenvironment for tumorigenesis. Our study also provides the information for designing more effective strategies to prevent or treat human cancers initiated by arsenic exposure.

Low doses of arsenic, via perturbing p53, promotes tumorigenesis

International Nuclear Information System (INIS)

Ganapathy, Suthakar; Li, Ping; Fagman, Johan; Yu, Tianqi; Lafontant, Jean; Zhang, Guojun; Chen, Changyan

2016-01-01

In drinking water and in workplace or living environments, low doses of arsenic can exist and operate as a potent carcinogen. Due to insufficient understanding and information on the pervasiveness of environmental exposures to arsenic, there is an urgent need to elucidate the underlying molecular mechanisms of arsenic regarding its carcinogenic effect on human health. In this study, we demonstrate that low doses of arsenic exposure mitigate or mask p53 function and further perturb intracellular redox state, which triggers persistent endoplasmic reticulum (ER) stress and activates UPR (unfolded protein response), leading to transformation or tumorigenesis. Thus, the results suggest that low doses of arsenic exposure, through attenuating p53-regulated tumor suppressive function, change the state of intracellular redox and create a microenvironment for tumorigenesis. Our study also provides the information for designing more effective strategies to prevent or treat human cancers initiated by arsenic exposure.

In-utero exposure to bereavement and offspring IQ: a Danish national cohort study.

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Jasveer Virk

Full Text Available BACKGROUND: Intelligence is a life-long trait that has strong influences on lifestyle, adult morbidity and life expectancy. Hence, lower cognitive abilities are therefore of public health interest. Our primary aim was to examine if prenatal bereavement measured as exposure to death of a close family member is associated with the intelligence quotient (IQ scores at 18-years of age of adult Danish males completing a military cognitive screening examination. METHODS: We extracted records for the Danish military screening test and found kinship links with biological parents, siblings, and maternal grandparents using the Danish Civil Registration System (N = 167,900. The prenatal exposure period was defined as 12 months before conception until birth of the child. We categorized children as exposed in utero to severe stress (bereavement during prenatal life if their mothers lost an elder child, husband, parent or sibling during the prenatal period; the remaining children were included in the unexposed cohort. Mean score estimates were adjusted for maternal and paternal age at birth, residence, income, maternal education, gestational age at birth and birth weight. RESULTS: When exposure was due to death of a father the offsprings' mean IQ scores were lower among men completing the military recruitment exam compared to their unexposed counterparts, adjusted difference of 6.5 standard IQ points (p-value = 0.01. We did not observe a clinically significant association between exposure to prenatal maternal bereavement caused by death of a sibling, maternal uncle/aunt or maternal grandparent even after stratifying deaths only due to traumatic events. CONCLUSION: We found maternal bereavement to be adversely associated with IQ in male offspring, which could be related to prenatal stress exposure though more likely is due to changes in family conditions after death of the father. This finding supports other literature on maternal adversity during fetal

Interactions of arsenic and phenanthrene on their uptake and antioxidative response in Pteris vittata L

International Nuclear Information System (INIS)

Sun Lu; Yan Xiulan; Liao Xiaoyong; Wen Yi; Chong Zhongyi; Liang Tao

2011-01-01

The interactions of arsenic and phenanthrene on plant uptake and antioxidative response of Pteris vitatta L. were studied hydroponically. The combination of arsenic and phenanthrene decreased arsenic contents in fronds by 30-51%, whereas increased arsenic concentrations 1.2-1.6 times in roots, demonstrating the suppression of arsenic translocation compared to the corresponding treatment without phenanthrene. Under the co-exposure, As(III) concentrations in fronds deceased by 12-73%, and at higher arsenic exposure level (≥10 mg/L), As(V) in fronds and As(III) in roots increased compared to the single arsenic treatment. Arsenic exposure elevated phenanthrene concentrations in root by 39-164%. The co-existence of arsenic and phenanthrene had little impact on plant arsenic accumulation, although synergistic effect on antioxidants was observed, suggesting the special physiological process of P. vitatta in the co-exposure and application potential of P. vitatta in phytoremediation of arsenic and PAHs co-contamination. - Highlights: → Pteris vitatta L. show tolerance to the arsenic and phenanthrene co-exposure. → P. vitatta efficiently accumulate arsenic and simultaneously enhance phenanthrene dissipation. → Phenanthrene suppresses arsenic translocation from roots to fronds. → Phenanthrene causes As(III) elevation in roots while reduction in fronds. → Synergistic effect potentiates the toxicity and antioxidants in plant. - Pteris vitatta L. not only efficiently accumulate arsenic but also enhance phenanthrene dissipation under the arsenic and phenanthrene co-exposure.

Interactions of arsenic and phenanthrene on their uptake and antioxidative response in Pteris vittata L

Energy Technology Data Exchange (ETDEWEB)

Sun Lu [Beijing Key Lab of Industrial Land Contamination and Remediation, Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences (CAS), Beijing 100101 (China); Graduate University of the Chinese Academy of Sciences, Beijing 100049 (China); Yan Xiulan [Beijing Key Lab of Industrial Land Contamination and Remediation, Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences (CAS), Beijing 100101 (China); Liao Xiaoyong, E-mail: liaoxy@igsnrr.ac.cn [Beijing Key Lab of Industrial Land Contamination and Remediation, Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences (CAS), Beijing 100101 (China); Wen Yi; Chong Zhongyi; Liang Tao [Beijing Key Lab of Industrial Land Contamination and Remediation, Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences (CAS), Beijing 100101 (China)

2011-12-15

The interactions of arsenic and phenanthrene on plant uptake and antioxidative response of Pteris vitatta L. were studied hydroponically. The combination of arsenic and phenanthrene decreased arsenic contents in fronds by 30-51%, whereas increased arsenic concentrations 1.2-1.6 times in roots, demonstrating the suppression of arsenic translocation compared to the corresponding treatment without phenanthrene. Under the co-exposure, As(III) concentrations in fronds deceased by 12-73%, and at higher arsenic exposure level ({>=}10 mg/L), As(V) in fronds and As(III) in roots increased compared to the single arsenic treatment. Arsenic exposure elevated phenanthrene concentrations in root by 39-164%. The co-existence of arsenic and phenanthrene had little impact on plant arsenic accumulation, although synergistic effect on antioxidants was observed, suggesting the special physiological process of P. vitatta in the co-exposure and application potential of P. vitatta in phytoremediation of arsenic and PAHs co-contamination. - Highlights: > Pteris vitatta L. show tolerance to the arsenic and phenanthrene co-exposure. > P. vitatta efficiently accumulate arsenic and simultaneously enhance phenanthrene dissipation. > Phenanthrene suppresses arsenic translocation from roots to fronds. > Phenanthrene causes As(III) elevation in roots while reduction in fronds. > Synergistic effect potentiates the toxicity and antioxidants in plant. - Pteris vitatta L. not only efficiently accumulate arsenic but also enhance phenanthrene dissipation under the arsenic and phenanthrene co-exposure.

Systems-level modeling the effects of arsenic exposure with sequential pulsed and fluctuating patterns for tilapia and freshwater clam

International Nuclear Information System (INIS)

Chen, W.-Y.; Tsai, J.-W.; Ju, Y.-R.; Liao, C.-M.

2010-01-01

The purpose of this paper was to use quantitative systems-level approach employing biotic ligand model based threshold damage model to examine physiological responses of tilapia and freshwater clam to sequential pulsed and fluctuating arsenic concentrations. We tested present model and triggering mechanisms by carrying out a series of modeling experiments where we used periodic pulses and sine-wave as featured exposures. Our results indicate that changes in the dominant frequencies and pulse timing can shift the safe rate distributions for tilapia, but not for that of freshwater clam. We found that tilapia increase bioenergetic costs to maintain the acclimation during pulsed and sine-wave exposures. Our ability to predict the consequences of physiological variation under time-varying exposure patterns has also implications for optimizing species growing, cultivation strategies, and risk assessment in realistic situations. - Systems-level modeling the pulsed and fluctuating arsenic exposures.

Systems-level modeling the effects of arsenic exposure with sequential pulsed and fluctuating patterns for tilapia and freshwater clam

Energy Technology Data Exchange (ETDEWEB)

Chen, W.-Y. [Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Tsai, J.-W. [Institute of Ecology and Evolutionary Ecology, China Medical University, Taichung 40402, Taiwan (China); Ju, Y.-R. [Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Liao, C.-M., E-mail: cmliao@ntu.edu.t [Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei 10617, Taiwan (China)

2010-05-15

The purpose of this paper was to use quantitative systems-level approach employing biotic ligand model based threshold damage model to examine physiological responses of tilapia and freshwater clam to sequential pulsed and fluctuating arsenic concentrations. We tested present model and triggering mechanisms by carrying out a series of modeling experiments where we used periodic pulses and sine-wave as featured exposures. Our results indicate that changes in the dominant frequencies and pulse timing can shift the safe rate distributions for tilapia, but not for that of freshwater clam. We found that tilapia increase bioenergetic costs to maintain the acclimation during pulsed and sine-wave exposures. Our ability to predict the consequences of physiological variation under time-varying exposure patterns has also implications for optimizing species growing, cultivation strategies, and risk assessment in realistic situations. - Systems-level modeling the pulsed and fluctuating arsenic exposures.

Association of Environmental Arsenic Exposure, Genetic Polymorphisms of Susceptible Genes, and Skin Cancers in Taiwan

Directory of Open Access Journals (Sweden)

Ling-I Hsu

2015-01-01

Full Text Available Deficiency in the capability of xenobiotic detoxification and arsenic methylation may be correlated with individual susceptibility to arsenic-related skin cancers. We hypothesized that glutathione S-transferase (GST M1, T1, and P1, reactive oxygen species (ROS related metabolic genes (NQO1, EPHX1, and HO-1, and DNA repair genes (XRCC1, XPD, hOGG1, and ATM together may play a role in arsenic-induced skin carcinogenesis. We conducted a case-control study consisting of 70 pathologically confirmed skin cancer patients and 210 age and gender matched participants with genotyping of 12 selected polymorphisms. The skin cancer risks were estimated by odds ratio (OR and 95% confidence interval (CI using logistic regression. EPHX1 Tyr113His, XPD C156A, and GSTT1 null genotypes were associated with skin cancer risk (OR = 2.99, 95% CI = 1.01–8.83; OR = 2.04, 95% CI = 0.99–4.27; OR = 1.74, 95% CI = 1.00–3.02, resp.. However, none of these polymorphisms showed significant association after considering arsenic exposure status. Individuals carrying three risk polymorphisms of EPHX1 Tyr113His, XPD C156A, and GSTs presented a 400% increased skin cancer risk when compared to those with less than or equal to one polymorphism. In conclusion, GSTs, EPHX1, and XPD are potential genetic factors for arsenic-induced skin cancers. The roles of these genes for arsenic-induced skin carcinogenesis need to be further evaluated.

Effects of different inorganic arsenic species in Cyprinus carpio (Cyprinidae) tissues after short-time exposure: Bioaccumulation, biotransformation and biological responses

International Nuclear Information System (INIS)

Ventura-Lima, Juliane; Fattorini, Daniele; Regoli, Francesco; Monserrat, Jose M.

2009-01-01

Differences in the toxicological and metabolic pathway of inorganic arsenic compounds are largely unknown for aquatic species. In the present study the effects of short-time and acute exposure to As III and As V were investigated in gills and liver of the common carp, Cyprinus carpio (Cyprinidae), measuring accumulation and chemical speciation of arsenic, and the activity of glutathione-S-transferase omega (GST Ω), the rate limiting enzyme in biotransformation of inorganic arsenic. Oxidative biomarkers included antioxidant defenses (total glutathione-S-transferases, glutathione reductase, glutathione, and glucose-6-phosphate dehydrogenase), total scavenging capacity toward peroxyl radicals, reactive oxygen species (ROS) measurement and lipid peroxidation products. A marked accumulation of arsenic was observed only in gills of carps exposed to 1000 ppb As V . Also in gills, antioxidant responses were mostly modulated through a significant induction of glucose-6-phosphate dehydrogenase activity which probably contributed to reduce ROS formation; however this increase was not sufficient to prevent lipid peroxidation. No changes in metal content were measured in liver of exposed carps, characterized by lower activity of GST Ω compared to gills. On the other hand, glutathione metabolism was more sensitive in liver tissue, where a significant inhibition of glutathione reductase was concomitant with increased levels of glutathione and higher total antioxidant capacity toward peroxyl radicals, thus preventing lipid peroxidation and ROS production. The overall results of this study indicated that exposure of C. carpio to As III and As V can induce different responses in gills and liver of this aquatic organism. - Common carp (Cyprinus carpio) presented marked differences between gills and liver after arsenic exposure in terms of antioxidant responses and also in biotransformation.

Time to revisit arsenic regulations: comparing drinking water and rice.

Science.gov (United States)

Sauvé, Sébastien

2014-05-17

Current arsenic regulations focus on drinking water without due consideration for dietary uptake and thus seem incoherent with respect to the risks arising from rice consumption. Existing arsenic guidelines are a cost-benefit compromise and, as such, they should be periodically re-evaluated. Literature data was used to compare arsenic exposure from rice consumption relative to exposure arising from drinking water. Standard risk assessment paradigms show that arsenic regulations for drinking water should target a maximum concentration of nearly zero to prevent excessive lung and bladder cancer risks (among others). A feasibility threshold of 3 μg As l(-1) was determined, but a cost-benefit analysis concluded that it would be too expensive to target a threshold below 10 μg As l(-1). Data from the literature was used to compare exposure to arsenic from rice and rice product consumption relative to drinking water consumption. The exposure to arsenic from rice consumption can easily be equivalent to or greater than drinking water exposure that already exceeds standard risks and is based on feasibility and cost-benefit compromises. It must also be emphasized that many may disagree with the implications for their own health given the abnormally high cancer odds expected at the cost-benefit arsenic threshold. Tighter drinking water quality criteria should be implemented to properly protect people from excessive cancer risks. Food safety regulations must be put in place to prevent higher concentrations of arsenic in various drinks than those allowed in drinking water. Arsenic concentrations in rice should be regulated so as to roughly equate the risks and exposure levels observed from drinking water.

Inorganic arsenic levels in baby rice are of concern

International Nuclear Information System (INIS)

Meharg, Andrew A.; Sun, Guoxin; Williams, Paul N.; Adomako, Eureka; Deacon, Claire; Zhu, Yong-Guan; Feldmann, Joerg; Raab, Andrea

2008-01-01

Inorganic arsenic is a chronic exposure carcinogen. Analysis of UK baby rice revealed a median inorganic arsenic content (n = 17) of 0.11 mg/kg. By plotting inorganic arsenic against total arsenic, it was found that inorganic concentrations increased linearly up to 0.25 mg/kg total arsenic, then plateaued at 0.16 mg/kg at higher total arsenic concentrations. Inorganic arsenic intake by babies (4-12 months) was considered with respect to current dietary ingestion regulations. It was found that 35% of the baby rice samples analysed would be illegal for sale in China which has regulatory limit of 0.15 mg/kg inorganic arsenic. EU and US food regulations on arsenic are non-existent. When baby inorganic arsenic intake from rice was considered, median consumption (expressed as μg/kg/d) was higher than drinking water maximum exposures predicted for adults in these regions when water intake was expressed on a bodyweight basis. - Median consumption of organic arsenic levels for UK babies from baby rice is above threshold considered safe

[Studies on markers of exposure and early effect in areas with arsenic pollution: methods and results of the project SEpiAs. Epidemiological surveillance in areas with environmental pollution by natural or anthropogenic arsenic].

Science.gov (United States)

Bustaffa, Elisa; Minichilli, Fabrizio; Andreassi, Maria Grazia; Carone, Simona; Coi, Alessio; Cori, Liliana; Faita, Francesca; Faita, Francesco; Grecchi, Sabina; Minoia, Claudio; Ronchi, Anna; Scovassi, Ivana; Sicari, Rosa; Stea, Francesco; Bianchi, Fabrizio

2014-01-01

Arsenic and its inorganic compounds are classified as carcinogenic to humans. Exposures to inorganic arsenic (iAs) in drinking water are associated with both carcinogenic and non-carcinogenic effects. The risk assessment of exposures to low-moderate levels of environmental arsenic (As) is a challenging objective for research and public health. The SEpiAs study, funded by the Italian Ministry of Health (CCM), was carried out in four areas with arsenic pollution prevalently of natural origin, Amiata and Viterbo areas, or of industrial origin, Taranto and Gela. 271 subjects (132 men) aged 20-44, were randomly sampled stratifying by area, gender and age classes. Individual data on residential history, socio-economic status, environmental and occupational exposures, lifestyle and dietary habits, were collected through interviews using questionnaire. In urine samples of recruited subjects, the concentration of inorganic arsenic (iAs) and methylated species (MMA, DMA) was measured using inductively coupled mass spectrometer (DRCICP- MS), after chromatographic separation (HPLC). Molecular biomarkers and biomarkers of DNA damage, as well as markers of cardiovascular risk were measured The distributions of iAs and iAs+MMA+DMA were described by area and gender, geometric mean (GM), percentiles and standard deviation (SD). The associations between As species and variables collected by questionnaire were evaluated by multiple regression analysis. Results showed a high variability of As species within and among areas. Gela and Taranto samples showed higher iAs concentration compared to Viterbo and Amiata. Subjects with iAs>1,5 μg/L or iAs+MMA+DMA>15 μg/L (thresholds suggested by the Italian Society of Reference Values), are 137 (50,6%) and 68 (25,1%), respectively. A positive association between iAs and use of drinking water emerged in the Viterbo sample, between iAs and occupational exposure in the Gela and Taranto samples. Fish consumption was associated with higher i

Antioxidative responses to arsenic in the arsenic-hyperaccumulator Chinese brake fern (Pteris vittata L.)

International Nuclear Information System (INIS)

Cao Xinde; Ma, Lena Q.; Tu Cong

2004-01-01

This study measured antioxidative responses of Chinese brake fern (Pteris vittata L.) upon exposure to arsenic (As) of different concentrations. Chinese brake fern was grown in an artificially-contaminated soil containing 0 to 200 mg As kg -1 (Na 2 HAsO 4 ) for 12 weeks in a greenhouse. Soil As concentrations at ≤20 mg kg -1 enhanced plant growth, with 12-71% biomass increase compared to the control. Such beneficial effects were not observed at >20 mg As kg -1 . Plant As concentrations increased with soil As concentrations, with more As being accumulated in the fronds (aboveground biomass) than in the roots and with maximum frond As concentration being 4675 mg kg -1 . Arsenic uptake by Chinese brake enhanced uptake of nutrient elements K, P, Fe, Mn, and Zn except Ca and Mg, whose concentrations mostly decreased. The contents of non-enzymatic antioxidants (glutathione, acid-soluble thiol) followed similar trends as plant As concentrations, increasing with soil As concentrations, with greater contents in the fronds than in the roots especially when exposed to high As concentrations (>50 mg kg -1 ). The activities of enzymatic antioxidants (superoxide dismutase, catalase, ascorbate peroxidase, guaiacol peroxidase) in Chinese brake followed the same trends as plant biomass, increasing with soil As up to 20 mg kg -1 and then decreased. The results indicated though both enzymatic and non-enzymatic antioxidants played significant roles in As detoxification and hyperaccumulation in Chinese brake, the former is more important at low As exposure (≤20 mg kg -1 ), whereas the latter is more critical at high As exposure (50-200 mg kg -1 ). - At low levels of arsenic exposure, enzymatic antioxidants are important for arsenic detoxification and accumulation in Chinese brake fern, while non-enzymatic antioxidants were more important at high arsenic exposure

In utero exposure to 25-hydroxyvitamin D and risk of childhood asthma, wheeze, and respiratory tract infections

DEFF Research Database (Denmark)

Feng, Haixia; Xun, Pengcheng; Pike, Katharine C

2017-01-01

BACKGROUND: Studies of the associations between in utero 25-hydroxyvitamin D (25[OH]D) exposure and risk of childhood asthma, wheeze, and respiratory tract infections are inconsistent and inconclusive. OBJECTIVES: We sought to assess associations between 25(OH)D levels in cord blood or maternal......)D is inversely associated with the risk of asthma and wheeze during childhood. These findings are in keeping with the results of 2 recently published randomized clinical trials of vitamin D supplementation during pregnancy....... venous blood and risk of offspring's asthma, wheeze, and respiratory tract infections. METHODS: Data were derived from PubMed, Embase, Google Scholar, references from relevant articles, and de novo results from published studies until December 2015. A random-effects meta-analysis was conducted among 16...

Arsenic speciation analysis of urine samples from individuals living in an arsenic-contaminated area in Bangladesh.

Science.gov (United States)

Hata, Akihisa; Yamanaka, Kenzo; Habib, Mohamed Ahsan; Endo, Yoko; Fujitani, Noboru; Endo, Ginji

2012-05-01

Chronic inorganic arsenic (iAs) exposure currently affects tens of millions of people worldwide. To accurately determine the proportion of urinary arsenic metabolites in residents continuously exposed to iAs, we performed arsenic speciation analysis of the urine of these individuals and determined whether a correlation exists between the concentration of iAs in drinking water and the urinary arsenic species content. The subjects were 165 married couples who had lived in the Pabna District in Bangladesh for more than 5 years. Arsenic species were measured using high-performance liquid chromatography and inductively coupled plasma mass spectrometry. The median iAs concentration in drinking water was 55 μgAs/L (range 47.9-153.4 μgAs/L), respectively. No arsenobetaine or arsenocholine was detected. The concentrations of the 4 urinary arsenic species were significantly and linearly related to each other. The urinary concentrations of total arsenic and each species were significantly correlated with the iAs concentration of drinking water. All urinary arsenic species are well correlated with each other and with iAs in drinking water. The most significant linear relationship existed between the iAs concentration in drinking water and urinary iAs + MMA concentration. From these results, combined with the effects of seafood ingestion, the best biomarker of iAs exposure is urinary iAs + MMA concentration.

Elucidating the selenium and arsenic metabolic pathways following exposure to the non-hyperaccumulating Chlorophytum comosum, spider plant

Science.gov (United States)

Afton, Scott E.; Catron, Brittany; Caruso, Joseph A.

2009-01-01

Although many studies have investigated the metabolism of selenium and arsenic in hyperaccumulating plants for phytoremediation purposes, few have explored non-hyperaccumulating plants as a model for general contaminant exposure to plants. In addition, the result of simultaneous supplementation with selenium and arsenic has not been investigated in plants. In this study, Chlorophytum comosum, commonly known as the spider plant, was used to investigate the metabolism of selenium and arsenic after single and simultaneous supplementation. Size exclusion and ion-pairing reversed phase liquid chromatography were coupled to an inductively coupled plasma mass spectrometer to obtain putative metabolic information of the selenium and arsenic species in C. comosum after a mild aqueous extraction. The chromatographic results depict that selenium and arsenic species were sequestered in the roots and generally conserved upon translocation to the leaves. The data suggest that selenium was directly absorbed by C. comosum roots when supplemented with SeVI, but a combination of passive and direct absorption occurred when supplemented with SeIV due to the partial oxidation of SeIV to SeVI in the rhizosphere. Higher molecular weight selenium species were more prevalent in the roots of plants supplemented with SeIV, but in the leaves of plants supplemented with SeVI due to an increased translocation rate. When supplemented as AsIII, arsenic is proposed to be passively absorbed as AsIII and partially oxidized to AsV in the plant root. Although total elemental analysis demonstrates a selenium and arsenic antagonism, a compound containing selenium and arsenic was not present in the general aqueous extract of the plant. PMID:19273464

LACK OF DNA SINGLE STRAND BREAKS IN A LUNG EPITHELIAL CELL LINE AFTER EXPOSURE TO ARSENIC

Science.gov (United States)

Arsenic (As) is a carcinogen whose most important target organs include the skin and lungs. Exposure can occur via water ingestion, or inhalation, as As is a by-product of fossil fuel combustion and other industrial activities. The carcinogenic mechanism of action for As remains ...

Atherosclerosis induced by arsenic in drinking water in rats through altering lipid metabolism

International Nuclear Information System (INIS)

Cheng, Tain-Junn; Chuu, Jiunn-Jye; Chang, Chia-Yu; Tsai, Wan-Chen; Chen, Kuan-Jung; Guo, How-Ran

2011-01-01

Arsenic in drinking water is a global environmental health problem, and the exposure may increase cardiovascular and cerebrovascular diseases mortalities, most likely through causing atherosclerosis. However, the mechanism of atherosclerosis formation after arsenic exposure is still unclear. To study the mechanism of atherosclerosis formation after arsenic exposure and explore the role of high cholesterol diet (HCD) in this process, we fed spontaneous hypertensive rats and Wistar Kyoto rats with basal diet or HCD and provided with them drinking water containing arsenic at different ages and orders for 20 consecutive weeks. We measured high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, heat shock protein 70 (HSP 70), and high sensitive C-reactive protein (hs-CRP) at predetermined intervals and determined expressions of cholesteryl ester transfer protein-1 (CETP-1) and liver X receptor β (LXRβ) in the liver. Atherosclerosis was determined by examining the aorta with hematoxylin and eosin stain. After 20 weeks, we found arsenic, alone or combined with HCD, may promote atherosclerosis formation with transient increases in HSP 70 and hs-CRP. Early combination exposure decreased the HDL-C/LDL-C ratio without changing the levels of total cholesterol and triglyceride until 30 weeks old. Both CETP-1 and LXRβ activities were suppressed, most significantly in early combination exposure. In conclusion, arsenic exposure may induce atherosclerosis through modifying reverse cholesterol transport in cholesterol metabolism and suppressing LXRβ and CEPT-1 expressions. For decreasing atherosclerosis related mortality associated with arsenic, preventing exposure from environmental sources in early life is an important element. - Highlights: → Arsenic causes cardiovascular and cerebrovascular diseases through atherosclerosis. → Arsenic may promote atherosclerosis with transient increase in HSP 70 and hs

Arsenic exposure and adverse health effects: a review of recent findings from arsenic and health studies in Matlab, Bangladesh.

Science.gov (United States)

Yunus, Mohammad; Sohel, Nazmul; Hore, Samar Kumar; Rahman, Mahfuzar

2011-09-01

The recent discovery of large-scale arsenic (As) contamination of groundwater has raised much concern in Bangladesh. Reliable estimates of the magnitude of As exposure and related health problems have not been comprehensively investigated in Bangladesh. A large population-based study on As and health consequences in Matlab (AsMat) was done in Matlab field site where International Centre for Diarrhoeal Disease Research, Bangladesh has maintained a health and demographic surveillance system registering prospectively all vital events. Taking advantage of the health and demographic surveillance system and collecting data on detailed individual level As exposure using water and urine samples, AsMat investigated the morbidity and mortality associated with As exposure. Reviews of findings to date suggest the adverse effects of As exposure on the risk of skin lesions, high blood pressure, diabetes mellitus, chronic disease, and all-cause infant and adult disease mortality. Future studies of clinical endpoints will enhance our knowledge gaps and will give directions for disease prevention and mitigations. Copyright © 2011. Published by Elsevier B.V.

Environmental arsenic exposure from a coal-burning power plant as a potential risk factor for nonmelanoma skin carcinoma: Results from a case-control study in the district of Prievidza, Slovakia

Energy Technology Data Exchange (ETDEWEB)

Pesch, B.; Ranft, U.; Jakubis, P.; Nieuwenhuijsen, M.J.; Hergemoller, A.; Unfried, K.; Jakubis, M.; Miskovic, P.; Keegan, T. [University of Dusseldorf, Dusseldorf (Germany)

2002-05-01

To investigate the risk of arsenic exposure from a coal-burning power plant in Slovakia on nonmelanoma skin cancer (NMSC) development, a 1996-1999 population-based case-control study was conducted with 264 cases and 286 controls. Exposure assessment was based on residential history and annual emissions (Asres1, Asres2) and on nutritional habits and arsenic content in food (Asnut1, Asnut2). Asres1 was assessed as a function of the distance of places of residence to the plant. Asres2 additionally considered workplace locations. Asnut1 was used to calculate arsenic uptake by weighting food frequencies with arsenic concentrations and annual consumption of food items. Asnut2 additionally considered consumption of local products. Age- and gender-adjusted risk estimates for NMSC in the highest exposure category (90th vs. 30th percentile) were 1.90 (95% confidence interval (CI): 1.39, 2.60) for Asres1, 1.90 (95% CI: 1.38, 2.62) for Asres2, 1.19 (95% CI: 0.64, 2.12) for Asnut1, and 1.83 (95% CI: 0.98, 3.43) for Asnut2. No interaction was found between arsenic exposure and dietary and residential data. Other plant emissions could have confounded the distance-based exposure variables. Consumption of contaminated vegetables and fruits could be confounded by the protective effects of such a diet. Nevertheless, the authors found an excess NMSC risk for environmental arsenic exposure.

Early Determinants of Obesity: Genetic, Epigenetic, and In Utero Influences

Directory of Open Access Journals (Sweden)

Kyung E. Rhee

2012-01-01

Full Text Available There is an emerging body of work indicating that genes, epigenetics, and the in utero environment can impact whether or not a child is obese. While certain genes have been identified that increase one’s risk for becoming obese, other factors such as excess gestational weight gain, gestational diabetes mellitus, and smoking can also influence this risk. Understanding these influences can help to inform which behaviors and exposures should be targeted if we are to decrease the prevalence of obesity. By helping parents and young children change certain behaviors and exposures during critical time periods, we may be able to alter or modify one’s genetic predisposition. However, further research is needed to determine which efforts are effective at decreasing the incidence of obesity and to develop new methods of prevention. In this paper, we will discuss how genes, epigenetics, and in utero influences affect the development of obesity. We will then discuss current efforts to alter these influences and suggest future directions for this work.

Sex-Dependent Effects of the Histone Deacetylase Inhibitor, Sodium Valproate, on Reversal Learning After Developmental Arsenic Exposure

Directory of Open Access Journals (Sweden)

Christina R. Steadman Tyler

2018-06-01

Full Text Available Several studies have demonstrated that exposure to arsenic in drinking water adversely affects brain development and cognitive function in adulthood. While the mechanism by which arsenic induces adverse neurological outcomes remains elusive, studies suggest a link between reduced levels of histone acetylation and impaired performance on a variety of behavioral tasks following arsenic exposure. Using our developmental arsenic exposure (DAE paradigm, we have previously reported reduced histone acetylation and associated histone acetyltransferase enzyme expression in the frontal cortex of C57BL/6J adult male mice, with no changes observed in the female frontal cortex. In the present study, we sought to determine if DAE produced sex-dependent deficits in frontal cortical executive function using the Y-maze acquisition and reversal learning tasks, which are specific for assessing cognitive flexibility. Further, we tested whether the administration of valproic acid, a class I–IIa histone deacetylase inhibitor, was able to mitigate behavioral and biochemical changes resulting from DAE. As anticipated, DAE inhibited acquisition and reversal learning performance in adult male, but not female, mice. Valproate treatment for 2 weeks restored reversal performance in the male arsenic-exposed offspring, while not affecting female performance. Protein levels of HDACs 1, 2, and 5 were elevated following behavioral assessment but only in DAE male mice; restoration of appropriate HDAC levels occurred after valproate treatment and was concurrent with improved behavioral performance, particularly during reversal learning. Female frontal cortical levels of HDAC enzymes were not impacted by DAE or valproate treatment. Finally, mRNA expression levels of brain-derived neurotrophic factor, Bdnf, which has been implicated in the control of frontal cortical flexibility and is regulated by HDAC5, were elevated in DAE male mice and restored to normal levels following HDACi

Roxarsone, inorganic arsenic, and other arsenic species in chicken: a U.S.-based market basket sample.

Science.gov (United States)

Nachman, Keeve E; Baron, Patrick A; Raber, Georg; Francesconi, Kevin A; Navas-Acien, Ana; Love, David C

2013-07-01

Inorganic arsenic (iAs) causes cancer and possibly other adverse health outcomes. Arsenic-based drugs are permitted in poultry production; however, the contribution of chicken consumption to iAs intake is unknown. We sought to characterize the arsenic species profile in chicken meat and estimate bladder and lung cancer risk associated with consuming chicken produced with arsenic-based drugs. Conventional, antibiotic-free, and organic chicken samples were collected from grocery stores in 10 U.S. metropolitan areas from December 2010 through June 2011. We tested 116 raw and 142 cooked chicken samples for total arsenic, and we determined arsenic species in 65 raw and 78 cooked samples that contained total arsenic at ≥ 10 µg/kg dry weight. The geometric mean (GM) of total arsenic in cooked chicken meat samples was 3.0 µg/kg (95% CI: 2.5, 3.6). Among the 78 cooked samples that were speciated, iAs concentrations were higher in conventional samples (GM = 1.8 µg/kg; 95% CI: 1.4, 2.3) than in antibiotic-free (GM = 0.7 µg/kg; 95% CI: 0.5, 1.0) or organic (GM = 0.6 µg/kg; 95% CI: 0.5, 0.8) samples. Roxarsone was detected in 20 of 40 conventional samples, 1 of 13 antibiotic-free samples, and none of the 25 organic samples. iAs concentrations in roxarsone-positive samples (GM = 2.3 µg/kg; 95% CI: 1.7, 3.1) were significantly higher than those in roxarsone-negative samples (GM = 0.8 µg/kg; 95% CI: 0.7, 1.0). Cooking increased iAs and decreased roxarsone concentrations. We estimated that consumers of conventional chicken would ingest an additional 0.11 µg/day iAs (in an 82-g serving) compared with consumers of organic chicken. Assuming lifetime exposure and a proposed cancer slope factor of 25.7 per milligram per kilogram of body weight per day, this increase in arsenic exposure could result in 3.7 additional lifetime bladder and lung cancer cases per 100,000 exposed persons. Conventional chicken meat had higher iAs concentrations than did conventional antibiotic

Childhood leukaemia following medical diagnostic exposure to ionizing radiation in utero or after birth

International Nuclear Information System (INIS)

Wakeford, R.

2008-01-01

A statistical association between childhood leukaemia and an abdominal X-ray examination of the pregnant mother was first reported in 1956 from a case-control study of childhood cancer mortality conducted in Great Britain. This study, later called the Oxford Survey of Childhood Cancers (OSCC), was continued and eventually showed a highly statistically significant ∼50% proportional increase in the risk of childhood leukaemia associated with antenatal diagnostic radiography. The association has been confirmed by many case-control studies carried out around the world, the appropriately combined results of which show a highly statistically significant increase in risk that is compatible with the OSCC finding. There is no doubt about the reality of the statistical association, but a causal interpretation has been questioned. On balance, however, the evidence points to low-level irradiation of the fetus increasing the risk of leukaemia in childhood, with an excess relative risk coefficient of around 50 Gy -1 (equivalent to an excess absolute risk coefficient of about 3% Gy -1 ), although the uncertainty associated with these coefficients is considerable and they are likely to be overestimates. In contrast to exposure in utero, the evidence from case-control studies for an association between childhood leukaemia and postnatal exposure to medical diagnostic irradiation is equivocal and sometimes conflicting. Since standard radiation risk models predict that low-level exposure in the early years of life should produce an increased risk of childhood leukaemia that is roughly similar to that arising from fetal exposure, this absence of persuasive evidence is likely to be due to various problems with the studies. This is unfortunate given the rise in relatively high dose diagnostic procedures (e.g. paediatric CT scans) that would be predicted to materially increase the relative risk of childhood leukaemia. (authors)

Effects of different inorganic arsenic species in Cyprinus carpio (Cyprinidae) tissues after short-time exposure: Bioaccumulation, biotransformation and biological responses

Energy Technology Data Exchange (ETDEWEB)

Ventura-Lima, Juliane [Instituto de Ciencias Biologicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS (Brazil); Programa de Pos-Graduacao em Ciencias Fisiologicas - Fisiologia Animal Comparada (FURG), Rio Grande, RS (Brazil); Fattorini, Daniele; Regoli, Francesco [Istituto di Biologia e Genetica, Universita Politecnica delle Marche, 60100, Ancona (Italy); Monserrat, Jose M., E-mail: josemmonserrat@pesquisador.cnpq.b [Instituto de Ciencias Biologicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS (Brazil); Programa de Pos-Graduacao em Ciencias Fisiologicas - Fisiologia Animal Comparada (FURG), Rio Grande, RS (Brazil)

2009-12-15

Differences in the toxicological and metabolic pathway of inorganic arsenic compounds are largely unknown for aquatic species. In the present study the effects of short-time and acute exposure to As{sup III} and As{sup V} were investigated in gills and liver of the common carp, Cyprinus carpio (Cyprinidae), measuring accumulation and chemical speciation of arsenic, and the activity of glutathione-S-transferase omega (GST OMEGA), the rate limiting enzyme in biotransformation of inorganic arsenic. Oxidative biomarkers included antioxidant defenses (total glutathione-S-transferases, glutathione reductase, glutathione, and glucose-6-phosphate dehydrogenase), total scavenging capacity toward peroxyl radicals, reactive oxygen species (ROS) measurement and lipid peroxidation products. A marked accumulation of arsenic was observed only in gills of carps exposed to 1000 ppb As{sup V}. Also in gills, antioxidant responses were mostly modulated through a significant induction of glucose-6-phosphate dehydrogenase activity which probably contributed to reduce ROS formation; however this increase was not sufficient to prevent lipid peroxidation. No changes in metal content were measured in liver of exposed carps, characterized by lower activity of GST OMEGA compared to gills. On the other hand, glutathione metabolism was more sensitive in liver tissue, where a significant inhibition of glutathione reductase was concomitant with increased levels of glutathione and higher total antioxidant capacity toward peroxyl radicals, thus preventing lipid peroxidation and ROS production. The overall results of this study indicated that exposure of C. carpio to As{sup III} and As{sup V} can induce different responses in gills and liver of this aquatic organism. - Common carp (Cyprinus carpio) presented marked differences between gills and liver after arsenic exposure in terms of antioxidant responses and also in biotransformation.

Induction of Human Squamous Cell-Type Carcinomas by Arsenic

International Nuclear Information System (INIS)

Martinez, V. D.; Becker-Santos, D. D.; Vucic, E. A.; Lam, S.; Lam, W. L.

2011-01-01

Arsenic is a potent human carcinogen. Around one hundred million people worldwide have potentially been exposed to this metalloid at concentrations considered unsafe. Exposure occurs generally through drinking water from natural geological sources, making it difficult to control this contamination. Arsenic biotransformation is suspected to have a role in arsenic-related health effects ranging from acute toxicities to development of malignancies associated with chronic exposure. It has been demonstrated that arsenic exhibits preference for induction of squamous cell carcinomas in the human, especially skin and lung cancer. Interestingly, keratins emerge as a relevant factor in this arsenic-related squamous cell-type preference. Additionally, both genomic and epi genomic alterations have been associated with arsenic-driven neoplastic process. Some of these aberrations, as well as changes in other factors such as keratins, could explain the association between arsenic and squamous cell carcinomas in humans.

Airborne arsenic and urinary excretion of arsenic metabolites during boiler cleaning operations in a Slovak coal-fired power plant

Energy Technology Data Exchange (ETDEWEB)

Yager, J.W.; Hicks, J.B.; Fabianova, N. [EPRI, Palo Alto, CA (United States). Environment Group

1997-08-01

Little information is available on the relationship between occupational exposure to inorganic arsenic in coal fly ash and urinary excretion of arsenic metabolites. This study was undertaken in a coal-fired power plant in Slovakia during a routine maintenance outage. Arsenic was measured in the breathing zone of workers during 5 consecutive workdays, and urine samples were obtained for analysis of arsenic metabolites-inorganic arsenic (As), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) prior to the start of each shift. Results from a small number of cascade impacter air samples indicated that approximately 90% of total particle mass and arsenic was present in particle size fractions {ge} 3.5 {mu}m. The 8-hr time-weighted average (TWA) mean arsenic air concentration was 48.3 {mu}g/m{sup 3} (range 0.17-375.2) and the mean sum of urinary arsenic (Sigma As) metabolites was 16.9 {mu}g As/g creatinine (range 2.6-50.8). For an 8-hr TWA of 10 {mu}g/m{sup 3} arsenic from coal fly ash, the predicted mean concentration f the Sigma As urinary metabolites was 13.2 {mu}g As/g creatinine. Comparisons with previously published studies of exposure to arsenic trioxide vapors and dusts in copper smelters suggest that bioavailability of arsenic from airborne coal fly ash (as indicated by urinary excretion) is about one-third that seen in smelters and similar settings. Arsenic compound characteristics, matrix composition, and particle size distribution probably play major roles in determining actual uptake of airborne arsenic.

The effects of in utero irradiation on mutation induction and transgenerational instability in mice

International Nuclear Information System (INIS)

Barber, Ruth C.; Hardwick, Robert J.; Shanks, Morag E.; Glen, Colin D.; Mughal, Safeer K.; Voutounou, Mariel; Dubrova, Yuri E.

2009-01-01

Epidemiological evidence suggests that the deleterious effects of prenatal irradiation can manifest during childhood, resulting in an increased risk of leukaemia and solid cancers after birth. However, the mechanisms underlying the long-term effects of foetal irradiation remain poorly understood. This study was designed to analyse the impact of in utero irradiation on mutation rates at expanded simple tandem repeat (ESTR) DNA loci in directly exposed mice and their first-generation (F 1 ) offspring. ESTR mutation frequencies in the germline and somatic tissues of male and female mice irradiated at 12 days of gestation remained highly elevated during adulthood, which was mainly attributed to a significant increase in the frequency of singleton mutations. The prevalence of singleton mutations in directly exposed mice suggests that foetal irradiation results in genomic instability manifested both in utero and during adulthood. The frequency of ESTR mutation in the F 1 offspring of prenatally irradiated male mice was equally elevated across all tissues, which suggests that foetal exposure results in transgenerational genomic instability. In contrast, maternal in utero exposure did not affect the F 1 stability. Our data imply that the passive erasure of epigenetic marks in the maternal genome can diminish the transgenerational effects of foetal irradiation and therefore provide important clues to the still unknown mechanisms of radiation-induced genomic instability. The results of this study offer a plausible explanation for the effects of in utero irradiation on the risk of leukaemia and solid cancers after birth.

Urinary arsenic profiles reveal exposures to inorganic arsenic from private drinking water supplies in Cornwall, UK

Science.gov (United States)

Middleton, D. R. S.; Watts, M. J.; Hamilton, E. M.; Ander, E. L.; Close, R. M.; Exley, K. S.; Crabbe, H.; Leonardi, G. S.; Fletcher, T.; Polya, D. A.

2016-05-01

Private water supplies (PWS) in Cornwall, South West England exceeded the current WHO guidance value and UK prescribed concentration or value (PCV) for arsenic of 10 μg/L in 5% of properties surveyed (n = 497). In this follow-up study, the first of its kind in the UK, volunteers (n = 207) from 127 households who used their PWS for drinking, provided urine and drinking water samples for total As determination by inductively coupled plasma mass spectrometry (ICP-MS) and urinary As speciation by high performance liquid chromatography ICP-MS (HPLC-ICP-MS). Arsenic concentrations exceeding 10 μg/L were found in the PWS of 10% of the volunteers. Unadjusted total urinary As concentrations were poorly correlated (Spearman’s ρ = 0.36 (P < 0.001)) with PWS As largely due to the use of spot urine samples and the dominance of arsenobetaine (AB) from seafood sources. However, the osmolality adjusted sum, U-AsIMM, of urinary inorganic As species, arsenite (AsIII) and arsenate (AsV), and their metabolites, methylarsonate (MA) and dimethylarsinate (DMA), was found to strongly correlate (Spearman’s ρ: 0.62 (P < 0.001)) with PWS As, indicating private water supplies as the dominant source of inorganic As exposure in the study population of PWS users.

Role and mechanism of arsenic in regulating angiogenesis.

Directory of Open Access Journals (Sweden)

Ling-Zhi Liu

Full Text Available Arsenic is a wide spread carcinogen associated with several kinds of cancers including skin, lung, bladder, and liver cancers. Lung is one of the major targets of arsenic exposure. Angiogenesis is the pivotal process during carcinogenesis and chronic pulmonary diseases, but the role and mechanism of arsenic in regulating angiogenesis remain to be elucidated. In this study we show that short time exposure of arsenic induces angiogenesis in both human immortalized lung epithelial cells BEAS-2B and adenocarcinoma cells A549. To study the molecular mechanism of arsenic-inducing angiogenesis, we find that arsenic induces reactive oxygen species (ROS generation, which activates AKT and ERK1/2 signaling pathways and increases the expression of hypoxia-inducible factor 1 (HIF-1 and vascular endothelial growth factor (VEGF. Inhibition of ROS production suppresses angiogenesis by decreasing AKT and ERK activation and HIF-1 expression. Inhibition of ROS, AKT and ERK1/2 signaling pathways is sufficient to attenuate arsenic-inducing angiogenesis. HIF-1 and VEGF are downstream effectors of AKT and ERK1/2 that are required for arsenic-inducing angiogenesis. These results shed light on the mechanism of arsenic in regulating angiogenesis, and are helpful to develop mechanism-based intervention to prevent arsenic-induced carcinogenesis and angiogenesis in the future.

Use of arsenic-73 in research supports USEPA's regulatory decisions on inorganic arsenic in drinking water*

Science.gov (United States)

Inorganic arsenic is a natural contaminant of drinking water in the United States and throughout the world. Long term exposure to inorganic arsenic in drinking water at elevated levels (>100 ug/L) is associated with development of cancer in several organs, cardiovascular disease,...

Factors Affecting Arsenic Methylation in Arsenic-Exposed Humans: A Systematic Review and Meta-Analysis.

Science.gov (United States)

Shen, Hui; Niu, Qiang; Xu, Mengchuan; Rui, Dongsheng; Xu, Shangzhi; Feng, Gangling; Ding, Yusong; Li, Shugang; Jing, Mingxia

2016-02-06

Chronic arsenic exposure is a critical public health issue in many countries. The metabolism of arsenic in vivo is complicated because it can be influenced by many factors. In the present meta-analysis, two researchers independently searched electronic databases, including the Cochrane Library, PubMed, Springer, Embase, and China National Knowledge Infrastructure, to analyze factors influencing arsenic methylation. The concentrations of the following arsenic metabolites increase (piAs), monomethyl arsenic (MMA), dimethyl arsenic (DMA), and total arsenic. Additionally, the percentages of iAs (standard mean difference (SMD): 1.00; 95% confidence interval (CI): 0.60-1.40; p< 0.00001) and MMA (SMD: 0.49; 95% CI: 0.21-0.77; p = 0.0006) also increase, while the percentage of DMA (SMD: -0.57; 95% CI: -0.80--0.31; p< 0.0001), primary methylation index (SMD: -0.57; 95% CI: -0.94--0.20; p = 0.002), and secondary methylation index (SMD: -0.27; 95% CI: -0.46--0.90; p = 0.004) decrease. Smoking, drinking, and older age can reduce arsenic methylation, and arsenic methylation is more efficient in women than in men. The results of this analysis may provide information regarding the role of arsenic oxidative methylation in the arsenic poisoning process.

Elevated lactate dehydrogenase activity and increased cardiovascular mortality in the arsenic-endemic areas of southwestern Taiwan

Energy Technology Data Exchange (ETDEWEB)

Liao, Ya-Tang [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Taiwan (China); Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taiwan (China); Genomics Research Center, Academia Sinica, Taiwan (China); Chen, Chien-Jen [Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taiwan (China); Genomics Research Center, Academia Sinica, Taiwan (China); Li, Wan-Fen [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Taiwan (China); Hsu, Ling-I [Genomics Research Center, Academia Sinica, Taiwan (China); Tsai, Li-Yu; Huang, Yeou-Lih [Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Taiwan (China); Sun, Chien-Wen [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Taiwan (China); Chen, Wei J., E-mail: wjchen@ntu.edu.tw [Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taiwan (China); Genetic Epidemiology Core Laboratory, National Taiwan University Center for Genomic Medicine, Taiwan (China); Wang, Shu-Li, E-mail: slwang@nhri.org.tw [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Taiwan (China); Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan (China)

2012-08-01

Arsenic ingestion has been linked to increasing global prevalence of and mortality from cardiovascular disease (CVD); arsenic can be removed from drinking water to reduce related health effects. Lactate dehydrogenase (LDH) is used for the evaluation of acute arsenic toxicity in vivo and in vitro, but it is not validated for the evaluation of long-term, chronic arsenic exposure. The present study examined the long-term effect of chronic arsenic exposure on CVD and serum LDH levels, after consideration of arsenic metabolism capacity. A total of 380 subjects from an arseniasis-endemic area and 303 from a non-endemic area of southwestern Taiwan were recruited in 2002. Various urinary arsenic species were analyzed using high-performance liquid chromatography (HPLC) and hydride generation systems. Fasting serum was used for quantitative determination of the total LDH activity. A significant dose–response relationship was observed between arsenic exposure and LDH elevation, independent of urinary arsenic profiles (P < 0.001). Furthermore, abnormal LDH elevation was associated with CVD mortality after adjustment for Framingham risk scores for 10-year CVD and arsenic exposure (hazard ratio, 3.98; 95% confidence interval, 1.07–14.81). LDH was elevated in subjects with arsenic exposure in a dose-dependent manner. LDH is a marker of arsenic toxicity associated with CVD mortality. Results of this study have important implications for use in ascertaining long-term arsenic exposure risk of CVD. -- Highlights: ► We showed that arsenic exposure was correlated with LDH elevation. ► LDH elevation was related to arsenic methylation capacity. ► Abnormal LDH elevation can be a marker of susceptibility to CVD mortality.

Elevated lactate dehydrogenase activity and increased cardiovascular mortality in the arsenic-endemic areas of southwestern Taiwan

International Nuclear Information System (INIS)

Liao, Ya-Tang; Chen, Chien-Jen; Li, Wan-Fen; Hsu, Ling-I; Tsai, Li-Yu; Huang, Yeou-Lih; Sun, Chien-Wen; Chen, Wei J.; Wang, Shu-Li

2012-01-01

Arsenic ingestion has been linked to increasing global prevalence of and mortality from cardiovascular disease (CVD); arsenic can be removed from drinking water to reduce related health effects. Lactate dehydrogenase (LDH) is used for the evaluation of acute arsenic toxicity in vivo and in vitro, but it is not validated for the evaluation of long-term, chronic arsenic exposure. The present study examined the long-term effect of chronic arsenic exposure on CVD and serum LDH levels, after consideration of arsenic metabolism capacity. A total of 380 subjects from an arseniasis-endemic area and 303 from a non-endemic area of southwestern Taiwan were recruited in 2002. Various urinary arsenic species were analyzed using high-performance liquid chromatography (HPLC) and hydride generation systems. Fasting serum was used for quantitative determination of the total LDH activity. A significant dose–response relationship was observed between arsenic exposure and LDH elevation, independent of urinary arsenic profiles (P < 0.001). Furthermore, abnormal LDH elevation was associated with CVD mortality after adjustment for Framingham risk scores for 10-year CVD and arsenic exposure (hazard ratio, 3.98; 95% confidence interval, 1.07–14.81). LDH was elevated in subjects with arsenic exposure in a dose-dependent manner. LDH is a marker of arsenic toxicity associated with CVD mortality. Results of this study have important implications for use in ascertaining long-term arsenic exposure risk of CVD. -- Highlights: ► We showed that arsenic exposure was correlated with LDH elevation. ► LDH elevation was related to arsenic methylation capacity. ► Abnormal LDH elevation can be a marker of susceptibility to CVD mortality.

Transcriptional Modulation of the ERK1/2 MAPK and NF-kB pathways in Human Urothelial cells after trivalent arsenical exposure: Implications for urinary bladder cancer

Science.gov (United States)

Chronic exposure to drinking water contaminated with inorganic arsenic (iAs) is associated with an increased risk ofurinary bladder (DB) cancers in humans. Rodent models administered particular arsenicals have indicated urothelial necrosis followed by regenerative proliferation i...

Gene expression, telomere and cognitive deficit analysis as a function of Chornobyl radiation dose and age: from in utero to adulthood

International Nuclear Information System (INIS)

Bazika, D.A.; Loganovs'kij, K.M.; Yil'jenko, Yi.M.; Chumak, S.A.; Bomko, M.O.

2015-01-01

The possible effects of low dose ionizing radiation on human cognitive function in adult hood and in utero was estimated. Cognitive tests, telomere length and expression of genes regulating telomere function were studied in Chornobyl cleanup workers who were exposed to doses under 500 mSv (n = 326) and subjects exposed in utero during the first days after the accident Prypiat town (n = 104). The neuro cognitive assessment covered memory, attention, language, executive and visiospatial functions. In young adults after prenatal exposure a relation ship was analyzed between a cognitive function and radiation dose to foetus, brain and thyroid gland. Internal controls were used for both groups - the group of Chornobyl cleanup workers exposed in doses less than 20 mSv and an age- matched comparison group from radioactively contaminated areas for subjects exposed in utero . This study shows that cognitive deficit in humans at a late period after radiation exposure is influenced by dose, age at exposure and gene regulation of telomere function

Low selenium status affects arsenic metabolites in an arsenic exposed population with skin lesions.

Science.gov (United States)

Huang, Zhi; Pei, Qiuling; Sun, Guifan; Zhang, Sichum; Liang, Jiang; Gao, Yi; Zhang, Xinrong

2008-01-01

The antagonistic effects between selenium (Se) and arsenic (As) suggest that low selenium status plays important roles in arsenism development. However, no study has been reported for humans suffering from chronic arsenic exposure with low selenium status. Sixty-three subjects were divided into 2 experimental groups by skin lesions (including hyperkeratosis, depigmentation, and hyperpigmentation). Total urine and serum concentrations of arsenic and selenium were determined by ICP-MS with collision/reaction cell. Arsenic species were analysed by ICP-MS coupled with HPLC. The mean concentration of As in the drinking waters was 41.5 microg/l. The selenium dietary intake for the studied population was 31.7 microg Se/d, and which for the cases and controls were 25.9 and 36.3 microg Se/d, respectively. Compared with the controls, the skin lesions cases had lower selenium concentrations in serum and urine (41.4 vs 49.6 microg/l and 71.0 vs 78.8 microg/l, respectively), higher inorganic arsenic (iAs) in serum (5.2 vs 3.4 microg/l, PiAs in serum and urine (20.2) vs 16.9% and 18.3 vs 14.5%, respectively, PiAs and its inhibition to be biotransformed to DMA occurred in human due to chronic exposure of low selenium status.

Alpha-lipoic acid protects oxidative stress, changes in cholinergic system and tissue histopathology during co-exposure to arsenic-dichlorvos in rats.

Science.gov (United States)

Dwivedi, Nidhi; Flora, Govinder; Kushwaha, Pramod; Flora, Swaran J S

2014-01-01

We investigated protective efficacy of α-lipoic acid (LA), an antioxidant against arsenic and DDVP co-exposed rats. Biochemical variables suggestive of oxidative stress, neurological dysfunction, and tissue histopathological alterations were determined. Male rats were exposed either to 50 ppm sodium arsenite in drinking water or in combination with DDVP (4 mg/kg, subcutaneously) for 10 weeks. α-Lipoic acid (50mg/kg, pos) was also co-administered in above groups. Arsenic exposure led to significant oxidative stress along, hepatotoxicity, hematotoxicity and altered brain biogenic amines levels accompanied by increased arsenic accumulation in blood and tissues. These altered biochemical variables were supported by histopathological examinations leading to oxidative stress and cell death. These biochemical alterations were significantly restored by co-administration of α-lipoic acid with arsenic and DDVP alone and concomitantly. The results indicate that arsenic and DDVP induced oxidative stress and cholinergic dysfunction can be significantly protected by the supplementation of α-lipoic acid. Copyright © 2013 Elsevier B.V. All rights reserved.

SSRI antidepressants: altered psychomotor development following exposure in utero?

Science.gov (United States)

2013-02-01

Selective serotonin reuptake inhibitor antidepressants (SSRIs) are sometimes prescribed to pregnant women. The potential consequences for the unborn child are gradually becoming clearer. In a case-control study of 298 children with autism and 1507 controls, 6.7% of mothers of autistic children had been prescribed an antidepressant during the year before delivery, compared to 3.3% of control mothers. The antidepressant was usually an SSRI. A dozen other small epidemiological studies of neurological development in children exposed to antidepressants in utero have provided mixed results. Two of these studies suggested a risk of psychomotor retardation. In practice, SSRI antidepressants should only be considered for pregnant women when non-drug measures fail and when symptoms are sufficiently serious to warrant drug therapy.

Arsenic in drinking water and lung cancer: A systematic review

International Nuclear Information System (INIS)

Celik, Ismail; Gallicchio, Lisa; Boyd, Kristina; Lam, Tram K.; Matanoski, Genevieve; Tao Xuguang; Shiels, Meredith; Hammond, Edward; Chen Liwei; Robinson, Karen A.; Caulfield, Laura E.; Herman, James G.; Guallar, Eliseo; Alberg, Anthony J.

2008-01-01

Exposure to inorganic arsenic via drinking water is a growing public health concern. We conducted a systematic review of the literature examining the association between arsenic in drinking water and the risk of lung cancer in humans. Towards this aim, we searched electronic databases for articles published through April 2006. Nine ecological studies, two case-control studies, and six cohort studies were identified. The majority of the studies were conducted in areas of high arsenic exposure (100 μg/L) such as southwestern Taiwan, the Niigata Prefecture, Japan, and Northern Chile. Most of the studies reported markedly higher risks of lung cancer mortality or incidence in high arsenic areas compared to the general population or a low arsenic exposed reference group. The quality assessment showed that, among the studies identified, only four assessed arsenic exposure at the individual level. Further, only one of the ecological studies presented results adjusted for potential confounders other than age; of the cohort and case-control studies, only one-half adjusted for cigarette smoking status in the analysis. Despite these methodologic limitations, the consistent observation of strong, statistically significant associations from different study designs carried out in different regions provide support for a causal association between ingesting drinking water with high concentrations of arsenic and lung cancer. The lung cancer risk at lower exposure concentrations remains uncertain

Atorvastatin acts synergistically with N-acetyl cysteine to provide therapeutic advantage against Fas-activated erythrocyte apoptosis during chronic arsenic exposure in rats

Energy Technology Data Exchange (ETDEWEB)

Biswas, Debabrata; Sen, Gargi; Sarkar, Avik; Biswas, Tuli

2011-01-01

Arsenic is an environmental toxicant that reduces the lifespan of circulating erythrocytes during chronic exposure. Our previous studies had indicated involvement of hypercholesterolemia and reactive oxygen species (ROS) in arsenic-induced apoptotic death of erythrocytes. In this study, we have shown an effective recovery from arsenic-induced death signaling in erythrocytes in response to treatment with atorvastatin (ATV) and N-acetyl cysteine (NAC) in rats. Our results emphasized on the importance of cholesterol in the promotion of ROS-mediated Fas signaling in red cells. Arsenic-induced activation of caspase 3 was associated with phosphatidylserine exposure on the cell surface and microvesiculation of erythrocyte membrane. Administration of NAC in combination with ATV, proved to be more effective than either of the drugs alone towards the rectification of arsenic-mediated disorganization of membrane structural integrity, and this could be linked with decreased ROS accumulation through reduced glutathione (GSH) repletion along with cholesterol depletion. Moreover, activation of caspase 3 was capable of promoting aggregation of band 3 with subsequent binding of autologous IgG and opsonization by C3b that led to phagocytosis of the exposed cells by the macrophages. NAC-ATV treatment successfully amended these events and restored lifespan of erythrocytes from the exposed animals almost to the control level. This work helped us to identify intracellular membrane cholesterol enrichment and GSH depletion as the key regulatory points in arsenic-mediated erythrocyte destruction and suggested a therapeutic strategy against Fas-activated cell death related to enhanced cholesterol and accumulation of ROS.

Approaches to increase arsenic awareness in Bangladesh: an evaluation of an arsenic education program.

Science.gov (United States)

George, Christine Marie; Factor-Litvak, Pam; Khan, Khalid; Islam, Tariqul; Singha, Ashit; Moon-Howard, Joyce; van Geen, Alexander; Graziano, Joseph H

2013-06-01

The objective of this study was to design and evaluate a household-level arsenic education and well water arsenic testing intervention to increase arsenic awareness in Bangladesh. The authors randomly selected 1,000 study respondents located in 20 villages in Singair, Bangladesh. The main outcome was the change in knowledge of arsenic from baseline to follow-up 4 to 6 months after the household received the intervention. This was assessed through a pre- and postintervention quiz concerning knowledge of arsenic. Respondents were between 18 and 102 years of age, with an average age of 37 years; 99.9% were female. The knowledge of arsenic quiz scores for study participants were significantly higher at follow-up compared with baseline. The intervention was effective in increasing awareness of the safe uses of arsenic-contaminated water and dispelling the misconception that boiling water removes arsenic. At follow-up, nearly all respondents were able to correctly identify the meaning of a red (contaminated) and green (arsenic safe) well relative to arsenic (99%). The educational program also significantly increased the proportion of respondents who were able to correctly identify the health implications of arsenic exposure. However, the intervention was not effective in dispelling the misconceptions in the population that arsenicosis is contagious and that illnesses such as cholera, diarrhea, and vomiting could be caused by arsenic. Further research is needed to develop effective communication strategies to dispel these misconceptions. This study demonstrates that a household-level arsenic educational program can be used to significantly increase arsenic awareness in Bangladesh.

Arsenic in drinking-water and risk for cancer in Denmark

DEFF Research Database (Denmark)

Baastrup, Rikke; Sørensen, Mette; Balstrøm, Thomas

2008-01-01

inconsistent results. Objective: To determine if exposure to low levels of arsenic in drinking-water in Denmark is associated with an increased risk for cancer. Methods: The study was based on a prospective Danish cohort of 57,053 persons in the Copenhagen and Aarhus areas. Cancer cases were identified......Background: Arsenic is a well-known carcinogen, which is often found in drinking-water. Epidemiological studies have shown increased cancer risks among individuals exposed to high concentrations of arsenic in drinking-water, while studies of the carcinogenic effect of low doses have had...... back to 1970. Average exposure for the cohort ranged between 0.05 and 25.3 µg/L (mean = 1.2 µg/L). Cox's regression models were used to analyze possible relationships between arsenic and cancer. Results: We found no significant association between exposure to arsenic and risk for cancers of the lung...

Inactivation of p15INK4b in chronic arsenic poisoning cases

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Aihua Zhang

2014-01-01

Full Text Available Arsenic exposure from burning high arsenic-containing coal has been associated with human skin lesion and cancer. However, the mechanisms of arsenic-related carcinogenesis are not fully understood. Inactivation of critical tumor suppression genes by epigenetic regulation or genetic modification might contribute to arsenic-induced carcinogenicity. This study aims to clarify the correlation between arsenic pollution and functional defect of p15INK4b gene in arsenic exposure residents from a region of Guizhou Province, China. To this end, 103 arsenic exposure residents and 105 control subjects were recruited in this study. The results showed that the exposure group exhibited higher levels of urinary and hair arsenic compared with the control group (55.28 vs 28.87 μg/L, 5.16 vs 1.36 μg/g. Subjects with higher arsenic concentrations are more likely to have p15INK4b methylation and gene deletion (χ2 = 4.28, P = 0.04 and χ2 = 4.31, P = 0.04. We also found that the degree of p15INK4b hypermethylation and gene deletion occurred at higher incidence in the poisoning cases with skin cancer (3.7% and 14.81% in non-skin cancer group, 41.18% and 47.06 in skin cancer group, and were significantly associated with the stage of skin lesions (χ2 = 12.82, P < 0.01 and χ2 = 7.835, P = 0.005. These observations indicate that inactivation of p15INK4b through genetic alteration or epigenetic modification is a common event that is associated with arsenic exposure and the development of arsenicosis.

Immunotoxicological effects of inorganic arsenic on gilthead seabream (Sparus aurata L.)

Energy Technology Data Exchange (ETDEWEB)

Guardiola, F.A.; Gónzalez-Párraga, M.P.; Cuesta, A. [Department of Cell Biology and Histology, Faculty of Biology, Campus Regional de Excelencia Internacional “Campus Mare Nostrum”, University of Murcia, 30100 Murcia (Spain); Meseguer, J. [Department of Cell Biology and Histology, Faculty of Biology, Campus Regional de Excelencia Internacional “Campus Mare Nostrum”, University of Murcia, 30100 Murcia (Spain); Department of Agricultural Chemistry, Geology and Pedology, Faculty of Chemistry, Campus Regional de Excelencia Internacional “Campus Mare Nostrum”, University of Murcia, 30100 Murcia (Spain); Martínez, S.; Martínez-Sánchez, M.J.; Pérez-Sirvent, C. [Department of Agricultural Chemistry, Geology and Pedology, Faculty of Chemistry, Campus Regional de Excelencia Internacional “Campus Mare Nostrum”, University of Murcia, 30100 Murcia (Spain); Esteban, M.A., E-mail: aesteban@um.es [Department of Cell Biology and Histology, Faculty of Biology, Campus Regional de Excelencia Internacional “Campus Mare Nostrum”, University of Murcia, 30100 Murcia (Spain)

2013-06-15

Highlights: •Short exposure to arsenic increases the hepato-somatic index and produces histopathological alterations in the liver. •Arsenic is bioaccumulated in the liver of gilthead seabream but no in the muscle. •Arsenic-exposure affects the innate immune system in the gilthead seabream. •Ten days of exposure to As enhances the immune parameters. -- Abstract: Arsenic (As) has been associated with multitude of animal and human health problems; however, its impact on host immune system has not been extensively investigated. In fish, there are very few works on the potential risks or problems associated to the presence of arsenic. In the present study we have evaluated the effects of exposure (30 days) to sub-lethal concentrations of arsenic (5 μM As{sub 2}O{sub 3}) in the teleost fish gilthead seabream (Sparus aurata), with special emphasis in the innate immune response. The arsenic concentration was determined using atomic fluorescence spectrometry (AFS) in liver and muscle of exposed fish showing As accumulation in the liver after 30 days of exposure. The hepatosomatic index was increased at significant extent after 10 days but returned to control values after 30 days of exposure. Histological alterations in the liver were observed including hypertrophy, vacuolization and cell-death processes. Focusing on the immunological response, the humoral immune parameters (seric IgM, complement and peroxidase activities) were no affected to a statistically significant extent. Regarding the cellular innate parameters, head-kidney leucocyte peroxidase, respiratory burst and phagocytic activities were significantly increased after 10 days of exposition compared to the control fish. Overall, As-exposure in the seabream affects the immune system. How this might interfere with fish biology, aquaculture management or human consumers warrants further investigations. This paper describes, for the first time, the immunotoxicological effects of arsenic exposure in the

Dietary arsenic consumption and urine arsenic in an endemic population: response to improvement of drinking water quality in a 2-year consecutive study.