Abstract  A variety of so-called innocuous chemicals can have insidious and long lasting effects on the developing male reproductive system. Developmental exposures of male rabbits to common industrial contaminants in drinking water (a mixture of arsenic, chromium, lead, benzene, chloroform, phenol, and trichloroethylene); alkyl phenols (e.g. octylphenol); water disinfection by-products (e.g. dibromoacetic acid); anti-androgenic pesticides (e.g. pp'-DDT and vinclozolin); and plasticizers (e.g. dibutyl phthalate) produce testicular dysgenesis. The lesions include testicular carcinoma in situ, also called intratubular germ cell neoplasia - the precursor lesion of germ cell tumors in men, and acrosomal dysgenesis - characterized by sharing of a dysplastic acrosome by two or more spermatids resulting in characteristic sperm acrosomal-nuclear malformations. Certain manifestations of testicular dysgenesis arch across environmental agents, and sequelae of intentional developmental exposures of rabbits duplicate what has been encountered in deer, horses, and humans for which the etiology is uncertain. (C) 2007 Elsevier B.V. All rights reserved.

Abstract  Large interindividual variability in urinary arsenic profiles, following chronic inorganic arsenic exposure, is well-known in humans. To understand this variability, we studied the relationship between polymorphisms in the gene for human monomethylarsonic acid (MMA(V)) reductase/hGSTO1 and the urinary arsenic profiles of individuals chronically exposed to arsenic in their drinking water. To ensure that we did not overlook rare polymorphisms, not included in the public databases, we amplified and sequenced all six exons of the gene and their flanking regions, using DNA isolated from peripheral blood samples of 75 subjects, living in the vicinity of Torreon, Mexico. Four groups, based on the levels of arsenic (9-100 microg/L) in their drinking water, were studied. We identified six novel polymorphisms and two reported previously. The novel polymorphisms were a three base pair deletion (delGGC) in the first intron; a G > C transversion, leading to a serine-to-cysteine substitution at amino acid 86; a G > T transversion and a A > T transversion in intron 5; a G > A transition resulting in glutamate-to-lysine substitution in amino acid 208; and a C > T transition producing an alanine-to-valine substitution in amino acid 236. Two subjects displayed significant differences in patterns of urinary arsenic; they had increased levels of urinary inorganic arsenic and reduced levels of methylated urinary arsenic species as compared to the rest of the study population. These two subjects had the same unique polymorphisms in hGSTO1 in that they were heterozygous for E155del and Glu208Lys. The identified SNPs may be one of the reasons for the large interindividual variability in the response of humans to chronic inorganic arsenic exposure. The findings suggest the need for further studies to identify unambiguously specific polymorphisms that may account for interindividual variability in the human response to chronic inorganic arsenic exposure.

Abstract  Arsenic (As) contamination of drinking water is considered a serious worldwide environmental health threat that is associated with increased disease risks including skin, lung, bladder and other cancers; type 2 diabetes; vascular and cardiovascular disease; reproductive and developmental effects; and neurological and cognitive effects. Increased health risks may occur at as low as 10-50 ppb, while biological effects have been observed in experimental animal and cell culture systems at much lower levels. We previously reported that As is a potent endocrine disruptor, altering gene regulation by the closely related glucocorticoid, mineralocorticoid, progesterone and androgen steroid receptors at concentrations as low as 0.01 µM ( 0.7 ppb). Very low doses enhanced hormone-mediated gene transcription whereas slightly higher but still non-cytotoxic doses were suppressive. We report here that As also disrupts the more distally related estrogen receptor (ER) both in vivo and in cell culture. At non-cytotoxic doses (1-50 µmol/kg arsenite) As strongly suppressed ER-dependent gene transcription of the 17ß-estradiol (E2)-inducible vitellogenin II gene in chick embryo liver in vivo. In cell culture, non-cytotoxic levels (0.25-3 µM, 20-225 ppb) of As significantly inhibited E2-mediated gene activation of an ER-regulated reporter gene and the native ER-regulated GREB1 gene in human breast cancer MCF-7 cells. While the effects of As on ER-dependent gene regulation were generally similar to As effects on the other steroid receptors, there were specific differences, particularly the lack of significant enhancement at the lowest doses, that may provide insights into possible mechanisms.

Abstract  OBJECTIVES: Chronic arsenic poisoning, due to ingestion of contaminated ground-water, is a major public health problem in West Bengal. It causes multiorgan damage. The present study attempts to objectively investigate the pulmonary involvement by examining the lung function. The nature of lung changes was also evaluated. MATERIAL AND METHODS: One hundred and seven subjects with (cases) and 52 subjects without (controls) chronic arsenic poisoning were examined by spirometry. Forced expiratory volume-I second (FEVI), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) were measured. Bronchoalveolar lavage (BAL) was performed in five cases with and five cases without pulmonary involvement. RESULTS: Thirty three (30.8%) cases and four (7.6%) controls (p<0.01) had respiratory involvement. The pattern of involvement in cases was: obstructive- 20(68.9%) (including three (10%) with bronchiectasis), restrictive- 1(3.5%), mixed- 8(27.6%), malignancy- 4(12.1%) (adenocarcinoma-I, squamous cell- 2, undifferentiated- I). FEVI (69.7+/-25.9 [n=105] vs 83.7+/-15.19 [n=51], p=0.0005), FVC (77.4+/-22.7 [n=105] vs 85.6+/-18.23 [n=51], p=0.025), FEVI/FVC (73.6+/-13.38 [n=105] vs 79.1+/-18.65 [n=52], p=0.007) and PEFR (53.9+/-21.52 [n= 103] vs 67.3+/-18.36 [n=51], p=0.0002) (percent of predicted) were all reduced more in cases compared to controls. Worsening of these parameters correlated with increasing degree of arsenic toxicity. Markers of inflammation (macrophage, lactate dehydrogenase, nitric oxide) were apparently more in the BAL fluid of those with lung involvement than in those without, though the arsenic content did not differ significantly. CONCLUSION: Chronic arsenic poisoning causes pulmonary involvement, predominantly obstructive, the degree of which worsens with increasing degree of arsenic toxicity. Inflammation, rather than direct toxicity, appears to be the underlying mechanism.

Abstract  In West Bengal, India, although more than 6 million people are exposed to arsenic through drinking water, only 15-20% showed arsenic-induced skin lesions, including premalignant hyperkeratosis. This indicates toward some factors that confer susceptibility to arsenic-induced carcinogenicity. In this work, we wanted to explore whether differences in DNA repair capacity could impart arsenic-induced carcinogenicity, through Comet assay, chromosomal aberration (CA) assay and challenge assay. Sixty arsenic exposed (30 individuals with arsenic-induced premalignant hyperkeratosis and 30 without skin lesion, but drinking similar arsenic contaminated water) and 30 arsenic unexposed individuals were recruited as study participants. Alkaline comet assay, and challenge assay were carried out in whole blood and CA study in lymphocytes to find out the DNA damage and DNA repair capacity in both hyperkeratotic and without skin lesion individuals. DNA damage as well as CA were found to be significantly higher in the arsenic-exposed individuals compared to unexposed individuals (p < 0.001). Within the exposed group, there was no significant difference as far as the level of DNA damage is concerned (p > 0.05), but CA was significantly higher in exposed individuals with hyperkeratosis than exposed individuals without hyperkeratosis (p < 0.01). Challenge assay showed that upon induction of DNA damage, the repair capacity in the exposed individuals with premalignant hyperkeratosis is significantly less (p < 0.001) than that of individuals without skin lesion, although the basal level of DNA damage was similar in both. Thus, the deficiency in DNA repair capacities in the hyperkeratotic individuals emerges as a prime contender for arsenic carcinogenicity.

Abstract  We hypothesized that chronic exposure to arsenic would deplete the reduced glutathione (GSH) and methionine in vivo, thereby impair the methylation capacity of inorganic arsenic (iAs) ingested. Our experiment was designed to explore the effects of exogenous GSH and methionine on arsenic methylation in mice exposed to arsenite via drinking water. Levels of iAs, monomethylarsenic acid (MMAs), and dimethylarsenic acid (DMAs) in the liver and blood were determined by the method of hydride generation coupled with atomic absorption spectrophotometry. Compared with mice exposed to arsenite alone, administration of GSH or methionine increased the secondary methylation index in the liver and primary methylation index in the blood, which resulted in the consequent increase of DMAs percent and decrease of iAs percent in the blood. Moreover, administration of GSH resulted in the increase of DMAs percent in the liver and total arsenic in the blood. Increase of total arsenic in the blood was mainly due to the increase of DMAs. Findings from the present study suggested that administration of GSH or methionine might potentiate the methylation capacity of arsenic in both liver and extrahepatic tissues, which may facilitate the excretion of arsenic and decrease arsenic related toxicities in the body.

Abstract  A pooled analysis of five biomonitoring studies was performed to assess the influence of hOGG1(326), XRCC1(399) and XRCC3(241) gene polymorphisms on micronuclei (MN) frequency in human peripheral blood lymphocytes, as measured by the ex vivo/in vitro cytokinesis-block micronucleus (CBMN) assay. Each study addressed a type of occupational exposure potentially able to induce DNA strand breakage (styrene, ionising radiation, cobalt/hard metal, welding fumes and inorganic arsenite compounds), and therefore MN, as a result of base excision repair and double-strand break repair deficiencies. The effect of genotype, age, exposure to genotoxic agents and smoking habit on MN induction was determined using Poisson regression analysis in 171 occupationally exposed male workers and in 132 non-exposed male referents. The analysis of genotype-genotype, genotype-smoking and genotype-exposure interactions by linear combinations of parameters showed significantly higher MN frequencies in the following subsets: (i) occupationally exposed workers carrying either the Thr/Thr or the Thr/Met XRCC3(241) genotypes compared to their referent counterparts (P < 0.001) and (ii) carriers of the Met/Met XRCC3(241) genotype compared to Thr/Thr XRCC3(241) carriers, as far as they are non-exposed and bear the variant (Ser/Cys or Cys/Cys) hOGG1(326) genotype (P < 0.01). Significantly lower MN frequencies were observed in carriers of the variant hOGG1(326) genotype compared to Ser/Ser hOGG1(326) carriers in the subgroup of non-smokers with Thr/Thr XRCC3(241) genotype (P < 0.01). Stratified analysis by occupational exposure showed a significant MN increase with smoking in occupationally exposed carriers of the Arg/Gln XRCC1(399)genotype (P < 0.001). In contrast, a significant MN decrease with smoking was observed in referents carrying the Ser/Ser hOGG1(326) genotype (P < 0.01). These findings provide evidence that the combination of different DNA repair genes and their interaction with environmental genotoxic agents may modulate MN induction. Understanding the complexity of the relationships between exposure, DNA repair and MN frequencies require larger scale studies and complementary biomarkers.

Abstract  BACKGROUND: Single-nucleotide polymorphisms in genes related to DNA repair capacity and ultraviolet exposure have not been well investigated in relation to skin lesions associated with arsenic exposure. This population based case-control study, of 600 cases and 600 controls, frequency matched on age and gender in Pabna, Bangladesh, in 2001-2002, investigated the association and potential effect modification between polymorphisms in Xeroderma Pigmentosum complementation group D (XPD) (Lys751Gln and Asp312Asn) genes, tendency to sunburn and arsenic-related skin lesions. METHODS: Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULT: No significant association was observed between skin lesions and the XPD 312 Asp/Asn (adjusted OR = 0.87, 95% CI = 0.65-1.15) Asn/Asn (adjusted OR = 0.76, 95% CI = 0.50-1.15) (referent Asp/Asp); XPD 751 Lys/Gln (adjusted OR = 0.92, 95% CI = 0.69-1.23) Gln/Gln (adjusted OR = 0.98, 95% CI = 0.66-1.45) (referent Lys/Lys). While we did not observe any evidence of effect modification of these polymorphisms on the association between well arsenic concentration and skin lesions, we did observe effect modification between these polymorphisms and sunburn tendency and arsenic-related skin lesions. Individuals with the heterozygote or homozygote variant forms (Asp/Asn or Asn/Asn) had half the risk of skin lesions (OR = 0.45, 95% CI = 0.29-0.68) compared with those with the wild-type XPDAsp312Asn genotype (Asp/Asp) and individuals with heterozygote or homozygote variant forms (Lys/Gln or Gln/Gln) had half the risk of skin lesions (OR = 0.47, 95% CI = 0.31-0.72) compared with those with the wild-type XPDLys751Gln genotype (Lys/Lys), within the least sensitive strata of sunburn severity. We observed effect modification on the multiplicative scale for XPD 751 and XPD 312. CONCLUSION: XPD polymorphisms modified the relationship between tendency to sunburn and skin lesions in an arsenic exposed population. Further study is necessary to explore the effect of XPD polymorphisms and sun exposure on risk of arsenic-related skin lesions.

Abstract  The potential effects of arsenic-contaminated drinking water on health are of concern, but our understanding of the risk factors of arsenicosis remains limited. This study assessed the prevalence of and socio-economic differentials in arsenic-associated skin lesions in a rural community in Bangladesh. Data were collected from a village where the Bangladesh Rural Advancement Committee has operated a health surveillance system and a community-based arsenic mitigation project since 1999. In total, 1654 residents in the study village were examined in May 2000 for arsenic-associated lesions on their skin. Socio-economic information was extracted from the surveillance system database covering the village. Nearly 2.9% of the study population had clinical manifestations of arsenic poisoning. The prevalence of arsenicosis was associated with age, sex, education and the economic status of the household. Multivariate analysis identified age and economic status as significant predictors of arsenicosis controlling for education and gender. In conclusion, a clear understanding of the socio-economic distribution of arsenicosis in different demographic and socio-economic groups will be useful in identifying the high-risk groups from arsenic-affected communities. More studies are needed to design effective interventions to mitigate the effects of arsenic in Bangladesh.

Abstract  Folate deficiency increases background levels of DNA damage and can enhance the genotoxicity of chemical agents. Arsenic, a known human carcinogen present in drinking water supplies around the world, induces chromosomal and DNA damage. The effect of dietary folate deficiency on arsenic genotoxicity was evaluated using a mouse peripheral blood micronucleus (MN) assay. In duplicate experiments, male C57Bl/6J mice were fed folate-deficient or folate-sufficient diets for 7 weeks. During week 7, mice on each diet were given four consecutive daily doses of sodium arsenite (0, 2.5, 5, or 10 mg/kg) via oral gavage. Over the course of the study the folate-deficient diet produced an approximate 60% depletion of red blood cell folate. Folate deficiency by itself was associated with small but significant increases in MN in normochromatic erythrocytes (NCEs) and polychromatic erythrocytes (PCEs). Arsenic exposure was associated with significant increases in MN-PCEs in both folate-deficient and folate-sufficient mice. MN-PCE frequencies at the 10 mg/kg dose of arsenic were increased 4.5-fold over vehicle control in folate-deficient mice and 2.1-fold over control in folate-sufficient mice. At the 5 and 10 mg/kg doses of arsenic, MN-PCE levels were significantly higher (1.3-fold and 2.4-fold, respectively) in folate-deficient mice compared to folate-sufficient mice. Very few MN from either control or treated animals in either experiment exhibited kinetochore immunostaining, suggesting that the MN were derived from chromosome breakage rather than from whole chromosome loss. These results indicate that folate deficiency enhances arsenic-induced clastogenesis at doses of 5 mg/kg and higher.

Abstract  OBJECTIVES: Consolidation of epidemiological data on pancreatic cancer and worksite exposures. METHODS: Publications during 1969-98 were surveyed. Studies without verified exposures were excluded. Meta-analyses were conducted on data from 92 studies covering 161 populations, with results for 23 agents or groups of agents. With a standard format, five epidemiologists extracted risk estimates and variables of the structure and quality of each study. The extracted data were centrally checked. Random meta-models were applied. RESULTS: Based on 20 populations, exposure to chlorinated hydrocarbon (CHC) solvents and related compounds was associated with a meta-risk ratio (MRR) of 1.4 (95% confidence interval (95% CI) 1.0 to 1.8). Nickel and nickel compounds were considered in four populations (1.9; 1.2 to 3.2). Excesses were found also for chromium and chromium compounds (1.4; 0.9 to 2.3), polycyclic aromatic hydrocarbons (PAHs) (1.5; 0.9 to 2.5), organochlorine insecticides (1.5; 0.6 to 3.7), silica dust (1.4; 0.9 to 2.0), and aliphatic and alicyclic hydrocarbon solvents (1.3; 0.8 to 2.8). Evidence on pancreatic carcinogenicity was weak or non-positive for the following agents: acrylonitrile (1.1; 0.0 to 6.2); arsenic (1.0; 0.6 to 1.5); asbestos (1.1; 0.9 to 1.5); diesel engine exhaust (1.0; 0.9 to 1.3); electromagnetic fields (1.1; 0.8 to 1.4); formaldehyde (0. 8; 0.5 to 1.0); flour dust (1.1; 0.3 to 3.2); cadmium and cadmium compounds (0.7; 0.4 to 1.4); gasoline (1.0; 0.8 to 1.2); herbicides (1.0; 0.8 to 1.3); iron and iron compounds (1.3; 0.7 to 2.5); lead and lead compounds (1.1; 0.8 to 1.5); man-made vitreous fibres (1.0; 0.6 to 1.6); oil mist (0.9; 0.8 to 1.0); and wood dust (1.1; 0.9 to 2.5). The occupational aetiological fraction of pancreatic cancer was estimated at 12%. In a subpopulation exposed to CHC solvents and related compounds, it was 29%; to chromium and chromium compounds, 23%; to nickel and nickel compounds, 47%; to insecticides, 33%; and to PAHs, 33%. CONCLUSION: Occupational exposures may increase risk of pancreatic cancer. High quality studies are called for on interactions between occupational, environmental, and lifestyle factors as well as interactions between genes and the environment.

Abstract  There is abundant epidemiological evidence that arsenic is an environmental carcinogen related to human cancers of the skin, lung, liver and urinary bladder, in particular. Dimethylarsinic acid (DMA) has also been reported to act as a carcinogen/or a promoter in rat models. To elucidate molecular mechanisms, we conducted an 18 month carcinogenicity study of DMA in p53 heterozygous (+/-) knockout mice, which are susceptible to early spontaneous development of various types of tumors, and wild-type (+/+) C57BL/6J mice. Totals of 88-90 males, 7-8 weeks of age, were divided into three groups each administered 0, 50 or 200 p.p.m. DMA in their drinking water for 18 months. Mice that were found moribund or died before the end of the study were autopsied to evaluate the tumor induction levels, as well as those killed at the end. Both p53(+/-) knockout and wild-type mice demonstrated spontaneous tumor development, but lesions were more prevalent in the knockout case. Carcinogenic effect of DMA was evident by significant early induction of tumors in both treated p53(+/-) knockout and wild-type mice, significant increase of the tumor multiplicity in 200 p.p.m.-treated p53(+/-) knockout mice, and by significant increase in the incidence and multiplicity of tumors (malignant lymphomas) in the treated wild-type mice. By the end of 80 weeks, tumor induction, particularly malignant lymphomas and sarcomas, were similar in treated and control p53(+/-) knockout mice. No evidence for organ-tumor specificity of DMA was obtained. Molecular analysis using PCR-SSCP techniques revealed no p53 mutations in lymphomas from either p53(+/-) knockout or wild-type mice. In conclusion, DMA primarily exerted its carcinogenic effect on spontaneous development of tumors with both of the animal genotypes investigated here.

Abstract  Inorganic arsenic (iAs), a known human carcinogen, acts as a tumor promoter in part by inducing a rapid burst of reactive oxygen species (ROS) in mammalian cells. This causes oxidative stress and a subsequent increase in the level of cellular glutathione (GSH). Glutathione, a ubiquitous reducing sulfhydryl tripeptide, is involved in ROS detoxification and its increase may be part of an adaptive response to the oxidative stress. Glutathione related enzymes including glutathione reductase (GR) and glutathioneS-transferase (GST) also play key roles in these processes. In this study the regulatory effects of inorganic arsenite (As(III)) on the activities of GSH-related enzymes were investigated in cultured human keratinocytes. Substantial increases in GR enzyme activity and mRNA levels were shown in keratinocytes and other human cell lines after exposure to low, subtoxic, micromolar concentrations of As(III) for 24 h. Upregulation of GSH synthesis paralleled the upregulation of GR as shown by increases in glutamate-cysteine lyase (GCL) enzyme activity and mRNA levels, cystine uptake, and intracellular GSH levels. Glutathione S-transferase activity was also shown to increase slightly in keratinocytes, but not in fibroblasts or breast tumor cells. Overall the results show that sublethal arsenic induces a multicomponent response in human keratinocytes that involves upregulation of parts, but not all of the GSH system and counteracts the acute toxic effects of iAs. The upregulation of GR has not previously been shown to be an integral part of this response, although GR is critical for maintaining levels of reduced GSH.

Abstract  Environmental arsenic exposure, through drinking contaminated water, is a significant risk factor for developing vascular diseases and is associated with liver portal hypertension, vascular shunting, and portal fibrosis through unknown mechanisms. We found that the addition of low doses of arsenite to the drinking water of mice resulted in marked pathologic remodeling in liver sinusoidal endothelial cells (SECs), including SEC defenestration, capillarization, increased junctional PECAM-1 expression, protein nitration, and decreased liver clearance of modified albumin. Furthermore, the pathologic changes observed after in vivo exposure were recapitulated in isolated mouse SECs exposed to arsenic in culture. To investigate the role of NADPH oxidase-generated ROS in this remodeling, we examined the effect of arsenite in the drinking water of mice deficient for the p47 subunit of the NADPH oxidase and found that knockout mice were protected from arsenite-induced capillarization and protein nitration. Furthermore, ex vivo arsenic exposure increased SEC superoxide generation, and this effect was inhibited by addition of a Nox2 inhibitor and quenched by the cellpermeant superoxide scavenger. In addition, inhibiting either oxidant generation or Rac1-GTPase blocked ex vivo arsenic-stimulated SEC differentiation and dysfunction. Our data indicate that a Nox2-based oxidase is required for SEC capillarization and that it may play a central role in vessel remodeling following environmentally relevant arsenic exposures. [ABSTRACT FROM AUTHOR] Copyright of Journal of Clinical Investigation is the property of American Society for Clinical Investigation and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)

Abstract  Environmental factors are considered key determinants of cardiovascular disease. Although lifestyle choices such as smoking, diet, and exercise are viewed as major environmental influences, the contribution of pollutants and environmental chemicals is less clear. Accumulating evidence suggests that exposure to pollutants and chemicals could elevate the risk of cardiovascular disease. Many epidemiological studies report that exposure to fine particles present in ambient air is associated with an increase in cardiovascular mortality. Statistically significant relationships between particulate air pollution and ischemic heart disease, arrhythmias, and heart failure have been reported. Animal studies show that exposure to ambient air particles increases peripheral thrombosis and atherosclerotic lesion formation. Exposures to arsenic, lead, cadmium, pollutant gases, solvents, and pesticides have also been linked to increased incidence of cardiovascular disease. Mechanistically, these effects have been attributed to changes in the synthesis or reactivity of nitric oxide that may be caused by environmental oxidants or increased endogenous production of reactive oxygen species. Additional studies are urgently needed to: identify the contribution of individual pollutants to specific aspects of cardiovascular disease; establish causality; elucidate the underlying physiological and molecular mechanisms; estimate the relative susceptibility of diseased and healthy individuals and that of specific population groups; and determine whether pollutant exposure are risk correlates, that is, whether they influence major risk factors, such as hypertension, cholesterol, or diabetes, or whether they contribute to the absolute risk of heart disease. Collectively, these investigations could contribute to the emergent field of environmental cardiology.

Abstract  Continuous flow (CF) chemical hydride generation (CHG) and electrochemical hydride generation (ECHG)irectly coupled to a novel 40W, atmospheric pressure, 2.45GHz microwave microstrip Ar plasma exiting a microstrip wafer has beeneveloped for the emission spectrometriceterminationf As and Sb using a miniaturizedptical fiber spectrometer and a CCD-arrayetector. The experimental conditions for both procedures wereptimized with respect to the relative netntensitiesf the As I 228.8 nm and Sb I 252.8 nm lines and their signal-to-backgroundntensity ratios. Additionally, the susceptibility tonterferences from Cd, Co, Cr, Cu, Fe, Ni, Pb and Zn andther hydride-forming elementsn theeterminationf As and Sb using the CHG and ECHG techniques wasnvestigatednetail. Under theptimized conditions,t was found that ECHGs more prone tonterferences compared to CHG. Theetection limits (3sigma)f As (6 ngmL(-1)) and Sb (7 ngmL(-1))btained for the ECHG-MSP-OES method are about three times lower thann the casef the CHG-MSP-OES methodue to a two-fold lower amountf H2ntroducednto the MSPn casef the ECHG, resultingn a better plasma stability and reduced background level. The linearity ranges for both calibration curves to a concentrationf up to 5 microgmL(-1) and a precision between 2% and 7% (2 microgmL(-1) and 0.050 microgmL(-1)f As and Sb, respectively) were found for both methods. Theeveloped ECHG-MSP-OES method was validated for As through the analysisf a certified coal fly ash standard reference material (NIST SRM 1633a) after sampleissolution. Theerived concentration (140+/-8 microgg(-1)) was found to agree well with the certifiedata (145+/-15 microgg(-1)). The method was also successfully applied to the analysisf both a galvanic bath sample, which contained Sb and was spiked with As, and a tap water sample spiked with both analytes. Recovery ratesf 99-101% and a Sb concentrationf 6.6 microgmL(-1)n the galvanic bath sample were revealed. The latter value showed a good agreement with theatabtained from ICP-OES analysis, which was also used for validation purpose.

Abstract  Exposure to environmental pollutants is an important problem of environmental toxicology. Heavy metals are regarded as toxic to living organisms because of their tendency to accumulate in selected tissues. Moreover, their presence is a causative agent of various sorts of disorders, including neuro-, nephro-, carcino-, terato-, and immunological. Exposures of human to environmental chemicals can occur simultaneously from various sources. One exposure route is ingestion of hazardous chemicals through contaminated food and beverages. Considering the above-mentioned menace, efforts should be focused on the estimation of dietary intakes of potential toxic agents by consumers. Dietary exposure assessment to nonnutrients is usually performed by combining 2 sets of data--the concentration of elemental contaminants in various food products and the consumption data of these food items. A variety of approaches exist for evaluating exposure to food chemicals, and the method chosen is influenced, among others, by the intended goal, the availability of data, cost, and time frame. Moreover, it is also important to note how accurate and detailed the information concerning toxic elements intake needs to be. There are a number of sources of food consumption data currently used in exposure assessments, which range from 1 d to habitual intake. Frequently, the heavy metals for which dietary exposure is of interest are present in trace and ultra-trace quantities. Hence, an analytical technique with sufficient sensitivity is required for the accurate determination of these chemicals in food samples. It is important to remember that the accuracy of quantitative analysis is strongly dependent on the sampling and preparation steps.

Abstract  The associations between toenail levels of five trace elements and breast cancer risk were studied among a cohort of 62, 641 US women who provided toenail clippings and were free from diagnosed breast cancer in 1982. Among 433 cases of breast cancer identified during 4 years of follow-up and their matched controls, the odds ratios comparing the highest with the lowest quintiles and adjusted for established breast cancer risk factors were as follows: for arsenic, 1.12 (95% confidence interval (CI) 0.66-1.91); for copper, 0.91 (95% CI 0.59-1.42); for chromium, 0.96 (95% Cl 0.61-1.52); for iron, 0.89 (95% CI 0.56-1.40); and for zinc, 1.09 (95% CI 0.70-1.70). Among postmenopausal women, a marginally significant positive association was observed between toenail chromium levels and breast cancer risk (odds ratio = 1.71, 95% Cl 0.87-3.35) (p for trend = 0.07). However, the association between chromium and breast cancer risk was inverse among premenopausal women. Although data on the validity of toenail levels of certain of these elements are limited, these results do not provide evidence for an important effect of arsenic, copper, chromium, iron, or zinc on breast cancer risk.

Abstract  The Rönnskär smelter in Skellefteå, Sweden, produces significant environmental pollutants, such as lead, arsenic, copper, cadmium and sulphur dioxide. The purpose of the present study was to determine whether children born to women living near the smelter during pregnancy had an increased risk of childhood cancer. The study group consisted of children born between 1961 and 1990 in the municipality of Skellefteå and parish of Holmsund. Through linkage to the Swedish Cancer Registry cancer diagnoses in the study group were obtained and compared with the expected ones based on the national incidence rates. Thirteen cases of childhood cancer were identified among children born in the vicinity of the smelter against 6.7 expected (SIR 195, 95%CI 88-300). Among distant born the observed number of cases (n = 42) was similar to that expected (n = 41.8).

Abstract  The solvent extraction of arsenic(V) was investigated using heptane containing ultrafine magnetite particles and hydrophobic ammonium salt. Arsenic(V) was favorably extracted from aqueous solutions of pH ranging over 2-7, where the distribution ratio (10(3)) was independent of the pH. Although the addition of alkyl ammonium salt improved the phase separation, no notable influence was observed on the extraction of arsenic(V). Oleic acid suppressed the distribution ratio of arsenic(V) when the concentration exceeded 10(-2) M. Sulfate did not interfere with the extraction, while the presence of more than 10(-3) M phosphate decreased the distribution ratio. Metal cations including calcium(II), manganese(II), cobalt(II), nickel(II), copper(II), zinc(II) and lanthanum(III) did not give any serious interference up to the 10(-4) M level. According to equilibrium and kinetic studies, the extraction of arsenic(V) can be interpreted by the adsorption of H2AsO4- onto the surface of dispersed magnetite particles. The relationship between the amount of arsenic(V) extracted in the organic phase and that remaining in an aqueous phase followed a Langmuir-type equilibrium equation. The maximum uptake capacity was determined to be 4.8 x 10(-4) mol/g-magnetite (36 mg As/g). The arsenic(V) extracted in the organic phase was quantitatively recovered by back-extraction with an alkaline solution.

Abstract  To explore the relation between respiratory cancer mortality and exposure to airborne arsenic, methods of conditional logistic regression analysis are applied to a matched case-control study of copper smelter employees in Montana. With follow-up data for the period 1938-1977, several measures of arsenic exposure are compared. For men first employed prior to 1925, three measures--the category of maximum arsenic exposure, cumulative arsenic exposure, and time-weighted average arsenic exposure--are good predictors of respiratory cancer mortality. Within this group, there was a significantly elevated relative risk of respiratory cancer mortality associated with medium and heavy exposure to arsenic. For men first employed during 1925-1947, time-weighted average exposure to arsenic (adjusted for age at first employment) is the best predictor. In this group, men with heavy arsenic exposure and initially employed at 16.9 years had a relative risk of 6.0 in comparison to the baseline group with only light exposure to arsenic and initially employed at 31.9 years. No particular advantage is found in lagging exposures 10 years prior to death of the case in each matched set.

Abstract  U-shaped response has been frequently encountered in various biological areas including epidemiology, toxicology, and oncology. Despite its frequent observation, the theory of U-shaped response has been crippled by the lack of a robust mechanism underlying and incomplete in vitro and in vivo correlation. In the present study, a novel mechanism is provided for a U-shaped response, based on the findings of agonist-induced vasomotor tone change affected by menadione (MEN) (synthetic vitamin K3), a reactive oxygen species generator, and arsenic, an environmental pollutant, which showed typical U-shaped responses in both in vitro aortic contractile response and in vivo blood pressure. U-shaped responses by MEN and arsenic were a combined result from heterogenic susceptibilities and responses of multiple target cells composing blood vessels, that is, endothelium and smooth muscle. Notably, endothelium, a regulator of vasomotor tone, was primarily affected by low-dose stimuli, whereas smooth muscle, an effector of vascular contraction, was affected later by high-dose. The dysfunction of smooth muscle was produced by high-dose MEN-induced hydrogen peroxide, resulting in the attenuation of vascular contractile reactivity, whereas low-dose MEN-induced superoxide led to the quenching of vasodilatory nitric oxide in endothelial cells, resulting in the enhancement of vasoconstriction. This mechanistic theory, the difference in susceptibilities and responses to a common stimulus between regulator and effector components of a system, could give a new insight into the explanation of various U-shaped responses and provide a new evidence for the need of the risk assessment of toxicants with a wider dose range.

Abstract  In a previous study we reported that methylation within the promoter region of p53 was altered in human lung A549 cells exposed to arsenite over a 2-week period in culture. In the present study the methylation status of the 5′ control region of the tumor suppressor gene, von Hippel Lindau syndrome (VHL), a gene known to be silenced transcriptionally by CpG methylation was assessed. No changes in DNA methylation in VHL in human kidney UOK cell lines exposed to arsenite were seen after 4 weeks in culture, assessed by simple HpaII digestion followed by PCR amplification. Using methylation-sensitive arbitrarily-primed PCR we identified eight differentially methylated regions of genomic DNA of 300–500 bp from three UOK cell lines and from human lung A549 cells after arsenite exposure in culture. Six fragments were hypermethylated, and two were hypomethylated, relative to untreated controls. Sequence analysis revealed two DNA fragments contained repeat sequences of mammalian-apparent LTR retrotransposons, five contained promoter-like sequences, and 13 CpG islands were identified. Three fragments had 99–100% homology to regions on human chromosomes 6, 9, and 15 but these genes have not yet been identified. Our findings are consistent with a potential role for both hypermethylation and hypomethylation of DNA that coexist after exposure to arsenite. The results, in total, could support the existence of a state of DNA methylation imbalance that could conceivably disrupt appropriate gene expression in arsenite exposed cells.

Abstract  BACKGROUND: Immigrant farmworkers are a population at risk for numerous environmental and occupational exposures. The metals arsenic, lead, mercury, and cadmium are known neurotoxins to which workers can be exposed both in the US and in their country of origin. Because farmworkers are exposed to neurotoxic pesticides, they may be at risk for adverse health effects from the combined exposure. OBJECTIVES: To examine the relationship between exposure to metals, as measured in urine, with personal and work-related characteristics of Mexican migrant and seasonal farmworkers in the US. METHODS: We analyzed data on metals found in urine of 258 farmworkers recruited from 44 camps in eastern North Carolina in 2007. Geometric means and 95% confidence intervals (CI) were used to compare data with data from the National Health and Nutrition Examination Survey (NHANES). We used multivariate regression models fitted for each metal to estimate the association of creatinine-corrected urinary metals and worker characteristics related to environmental and occupational exposures. RESULTS: Geometric mean urinary metals concentrations (mug/g creatinine) exceeded NHANES reference values for arsenic (13.23 [CI 11.11, 15.35] vs. 8.55 [CI 7.23, 9.86]) and lead (1.26 [CI 1.08, 1.43] vs. 0.63 [CI 0.60, 0.66]). Age, being from the central region of Mexico, and pack years of cigarette smoking were significant predictors of metals exposure; being a current smoker and years worked in US agriculture were not. CONCLUSIONS: This first study to examine indicators of worker body burdens of metals shows that workers have body burdens related to exposures other than work in the US. Further research should address their risk for adverse health outcomes due to combined exposures to neurotoxins in pesticides.

Abstract  This study determined the accumulation of selected heavy metals (Pb, Cd, Hg and As) in tissues of wild boar. The tested animals were divided into three age groups, which allowed analysis of the statistical/mathematical relationship between their age and contamination of their tissues. For determination of heavy metal content, samples were taken from the longissimus muscle of the back and from the tail lobe of the liver. It has been stated that, in wild boar, accumulation of lead and cadmium in muscle and liver increases with age. However, statistical differences were found most frequently between the youngest and oldest animal groups only. Moreover, in no single case, was the maximum permissible level exceeded in muscle for lead, cadmium or mercury, and arsenic was not detected above 0.001 mg/kg. In the >3 year group, the maximum permissible level of cadmium (0.5 mg/kg) was exceeded in two liver samples.