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PubMed2002

Use of hydrochloric acid for determinining solid-phase arsenic partitioning in sulfidic sediments.

We examined the use of room-temperature hydrochloric acid (1-6 M) and salt solutions of magnesium chloride, sodium carbonate, and sodium sulfide for the removal of arsenic from synthetic iron monosulfides and contaminated sediments containing acid-volatile sulfides (AVS). Results indicate that acid-soluble arsenic reacts with H2S released from AVS phases and precipitates at low pH as disordered orpiment or alacranite. Arsenic sulfide precipitation is consistent with geochemical modeling in that conditions during acid extraction are predicted to be oversaturated with respect to orpiment, realgar, or both. Binding of arsenic with sulfide at low pH is sufficiently strong that 6 M HCl will not keep spiked arsenic in the dissolved fraction. Over a wide range of AVS concentrations and molar [As]/[AVS] ratios, acid extraction of arsenic from sulfide-bearing sediments will give biased results that overestimate the stability or underestimate the bioavailability of sediment-bound arsenic. Alkaline solutions of sodium sulfide and sodium carbonate are efficient in removing arsenic from arsenic sulfides and mixed iron-arsenic sulfides because of the high solubility of arsenic at alkaline pH, the formation of stable arsenic complexes with sulfide or carbonate, or both.

Arsenic↗
PubMed2006

Landfill-stimulated iron reduction and arsenic release at the Coakley Superfund Site (NH).

Arsenic is a contaminant at more than one-third of all Superfund Sites in the United States. Frequently this contamination appearsto resultfrom geochemical processes rather than the presence of a well-defined arsenic source. Here we examine the geochemical processes that regulate arsenic levels at the Coakley Landfill Superfund Site (NH), a site contaminated with As, Cr, Pb, Ni, Zn, and aromatic hydrocarbons. Long-term field observations indicate that the concentrations of most of these contaminants have diminished as a result of treatment by monitored natural attenuation begun in 1998; however, dissolved arsenic levels increased modestly over the same interval. We attribute this increase to the reductive release of arsenic associated with poorly crystalline iron hydroxides within a glaciomarine clay layer within the overburden underlying the former landfill. Anaerobic batch incubations that stimulated iron reduction in the glaciomarine clay released appreciable dissolved arsenic and iron. Field observations also suggest that iron reduction associated with biodegradation of organic waste are partly responsible for arsenic release; over the five-year study period since a cap was emplaced to prevent water flow through the site, decreases in groundwater dissolved benzene concentrations at the landfill are correlated with increases in dissolved arsenic concentrations, consistent with the microbial decomposition of both benzene and other organics, and reduction of arsenic-bearing iron oxides. Treatment of contaminated groundwater increasingly is based on stimulating natural biogeochemical processes to degrade the contaminants. These results indicate that reducing environments created within organic contaminant plumes may release arsenic. In fact, the strong correlation (>80%) between elevated arsenic levels and organic contamination in groundwater systems at Superfund Sites across the United States suggests that arsenic contamination caused by natural degradation of organic contaminants may be widespread.

Arsenic↗
PubMed2004

Effects and interactions of low doses of arsenic and UVB on keratinocyte apoptosis.

Although arsenic and ultraviolet light B (UVB) are both causes for skin cancers, lesions of arsenic-induced Bowen's disease are often confined to sun-protected skin. UVB may play a modulatory role in skin carcinogenesis by arsenic. The purpose of this study was to evaluate the effects and interactions of arsenic and UVB on cell cycle progression and apoptosis. Cultured human keratinocytes were treated with sodium arsenite (1 microM) and/or UVB (50 mJ/cm(2)) irradiation in different combinations: (i) arsenic alone, (ii) UVB alone, (iii) arsenic followed by UVB (As-UVB), and (iv) UVB followed by arsenic (UVB-As) treatments. Cell cycle analysis and BrdU pulsing revealed S phase arrest in all treatment groups and growth arrest in As-UVB and UVB-As groups. The terminal deoxynucleotidyl transferase-mediated deoxyuridine nick-end labeling assay showed a higher apoptosis rate in the UVB-As group as compared to that of the As-UVB and UVB groups. UVB irradiation significantly decreased Bcl-2 expression. In either the As-UVB or the UVB-As group, the expression of Bcl-2 was further suppressed as compared to the UVB group. The caspase-3, -8, and -9 relative activities were all increased in the UVB group; however, arsenic significantly enhanced caspase-8 and -3 relative activities in UVB-irradiated keratinocytes (the UVB-As group). Pretreatment with the caspase inhibitor(s) rescued the keratinocytes viability to different degrees with the least in the UVB-As group. Our findings revealed that arsenic enhances UVB-induced keratinocyte apoptosis via suppression of Bcl-2 expression and stimulation of caspase-8 activity. Combined UVB and arsenic treatment resulted in the antiproliferative and proapoptotic effects in keratinocytes. Our results provide the explanation for the rare occurrences of arsenical cancers in the sun-exposed skin and the potential therapeutic role of UVB in arsenic-induced Bowen's disease.

Apoptosis↗
PubMed2003

Identifying US populations for the study of health effects related to drinking water arsenic.

The US Environmental Protection Agency recently set a new maximum contaminant level (MCL) for arsenic in drinking water of 10 micro g/l. In this paper, we review the completeness and accuracy of drinking water arsenic occurrence data in the United States and identify populations exposed to elevated arsenic concentrations that would be suitable for epidemiological studies of arsenic health effects. Using existing data from the Environmental Protection Agency Arsenic Occurrence and Exposure Database and additional data from state health and environment departments and water utilities, we identified 33 counties in 11 states with an estimated mean drinking water arsenic concentration of 10 micro g/l or greater. A total of 11 of these 'confirmed' counties had an estimated mean arsenic concentration of 20 micro g/l or more and two had an estimated mean arsenic concentration 50 micro g/l or more. Based on census data, between 1950 and 1999 there were approximately 51.1 million person-years of exposure to drinking water arsenic at levels of 10 micro g/l or more, 8.2 million at levels of 20 micro g/l or more arsenic and 0.9 million at levels of 50 micro g/l or more. Mortality and incidence of diseases known to be associated with arsenic exposure can and should be examined in these counties as part of a comprehensive assessment of arsenic health effects in US populations.

Arsenic↗
PubMed2001

Arsenic extraction and speciation in carrots using accelerated solvent extraction, liquid chromatography and plasma mass spectrometry.

Arsenic present in freeze-dried carrots was extracted using accelerated solvent extraction (ASE). Several parameters, including selection of the dispersing agent, extraction time, number of extraction cycles, particle size and extraction temperature, were evaluated to optimize the ASE method. Filtering and treatment with C-18 SPE cartridges were also evaluated as part of the sample preparation procedure before speciation analysis. The method was validated by spiking single arsenical and mixed arsenical standards on the dispersing agent and on portions of freeze-dried carrot prior to extraction. LC-ICP-MS was used to determine individual arsenic species in the carrot extracts. A weak anion-exchange column was used for the separation of As(III), As(v), monomethylarsonic acid (MMA), dimethylarsinic acid and arsenobetaine. Optimized sample preparation conditions were applied to the extraction of arsenic in nine freeze-dried carrot samples. Total arsenic concentration in the carrot samples ranged from less than 20 ng g(-1) to 18.7 microg g(-1), dry mass. Extraction efficiency, defined as the ratio of the sum of individual arsenic species concentrations to total arsenic, ranged from 80 to 102% for freeze-dried carrots with arsenic concentrations greater than the limit of quantitation. Inorganic As(III) and As(v) were the only species found in samples that contained less than 400 ng g(-1) total arsenic. MMA and an unidentified arsenic compound were present in some of the samples with higher total arsenic content.

Arsenic↗
PubMed2005

Processes conducive to the release and transport of arsenic into aquifers of Bangladesh.

Arsenic is a contaminant in the groundwater of Holocene aquifers in Bangladesh, where approximately 57 million people drink water with arsenic levels exceeding the limits set by the World Health Organization. Although arsenic is native to the sediments, the means by which it is released to groundwater remains unresolved. Contrary to the current paradigm, ferric (hydr)oxides appear to dominate the partitioning of arsenic in the near surface but have a limited impact at aquifer depths where wells extract groundwater with high arsenic concentrations. We present a sequence of evidence that, taken together, suggest that arsenic may be released in the near surface and then transported to depth. We establish that (i) the only portion of the sediment profile with conditions destabilizing to arsenic in our analysis is in the surface or near-surface environment; (ii) a consistent input of arsenic via sediment deposition exists; (iii) retardation of arsenic transport is limited in the aquifers; and (iv) groundwater recharge occurs at a rate sufficient to necessitate continued input of arsenic to maintain observed concentrations. Our analyses thus lead to the premise that arsenic is liberated in surface and near-surface sediments through cyclic redox conditions and is subsequently transported to well depth. Influx of sediment and redox cycling provide a long-term source of arsenic that when liberated in the near surface is only weakly partitioned onto sediments deeper in the profile and is transported through aquifers by groundwater recharge.

Arsenic↗
PubMed2002

Methylarsonic and dimethylarsinic acids toxicity and total arsenic accumulation in edible bush beans, Phaseolus vulgaris.

The main objective was to evaluate whether arsenic accumulated in the edible pods and seeds of Phaseolus vulgaris, cv. F15 above the Spanish maximum recommended concentration for food crops, 1 mg kg(-1) on a fresh weight basis. Only organic arsenicals, methylarsonic and dimethylarsinic acids were used because they were: (1) the only arsenic species allowed for agricultural applications and (2) more mobile than inorganic species. Selection of French beans, a sensitive plant to arsenic, was based on the fact that arsenic-upward translocation is higher in sensitive than in tolerant plants. A 2 x 3 factorial experiment was conducted with two organic arsenic species (methylarsonic acid, dimethylarsinic acid) and three arsenic concentrations (0.2, 0.5, 1.0 mg l(-1)). Experimental results showed that the low bean plant tolerance to arsenic was possibly due to the high arsenic-upward transport to shoots, which could result in profound negative metabolic consequences. Even under extreme adverse conditions, arsenic residues in edible beans were below the maximum statutory limit set by the Spanish legislation. It is concluded that the major drawback of organic arsenical herbicides is that of decreased productivity rather than high arsenic intake by consumers of edible products from sensitive plant species.

Arsenicals↗
PubMed1984

Significance of arsenic metabolic forms in urine. Part I: Chemical speciation.

The aim of this research has been to develop analytical procedures whereby the various chemical forms of arsenic present in urine can be distinguished and further data on the biotransformation of absorbed arsenic can be acquired. The separation of inorganic arsenic ( InAs ), monomethylarsonic acid ( MMAA ), and dimethylarsinic acid ( DMAA ) in urine was performed by ion-exchange chromatography on AG 50 W-X8 resin. Arsenic was then measured directly on the eluted fractions by atomic absorption spectrophotometry, after the reduction of arsenic to the correspondent arsine. In 160 subjects with no occupational exposure to arsenic compounds, InAs , MMAA , DMAA each accounted for about 10% of the total arsenic urinary excretion (17.2 +/- 11.1 micrograms/1), thus indicating that in the normal population over 60% of arsenic in urine is present in other organic forms. After eating marine food, there was a marked increase of urinary output of arsenic, but no increase was observed in InAs , MMAA and DMAA urinary excretion. In the biological monitoring of exposure to inorganic arsenic, particularly in the case of high urinary excretion values, the differentiation of the excreted forms of arsenic is necessary to establish with certainty the source (industrial or alimentary) of arsenic.

Adult↗
PubMed2006

Role of oxidative stress in arsenic-induced toxicity.

Arsenic is recognized as a carcinogen for human skin, bladder, and lung, following either ingestion or inhalation; however the exact mode of action of environmentally relevant exposure has not been determined. Because arsenic in the environment exists in several oxidative states and can interact with thiols, it is thought that arsenic toxicity is mediated through oxidative stress. Production of oxygen radicals following acute in vitro exposures has been demonstrated. However, our research has chosen to focus on the role of oxidative stress following whole animal exposure to environmentally relevant doses of arsenic. Following a 28-d inhalation of arsenic or cigarette smoke or both, there was a significant decrease in both the reduced and total glutathione levels in the combined arsenic and smoke group compared to groups exposed to arsenic or smoke alone. This correlated with a 5-fold increase in DNA oxidation. Lungs processed for immunohistochemistry localization of 8-oxo-dG showed increased staining in nuclei of airway epithelium and subadjacent interstitial cells. Increases in DNA oxidation were not due to increased inflammation. Although inhalation of arsenic is an important occupational exposure, the majority of human exposures occurs through ingestion of arsenic. Our recent work has been devoted to the identification of altered pulmonary gene and protein expression following ingestion of environmentally relevant levels of arsenic in drinking water. We have found that, following chronic exposure, arsenic leads to misregulation of a number of genes and proteins in the lung. A large percentage of the altered genes and proteins are known to be regulated by redox-sensitive transcription factors, (SP1, NF kappaB, AP-1), suggesting that, at environmentally relevant levels of chronic exposure, arsenic may be acting through alteration of cellular redox status. Validation of the alterations seen in animal models of exposure is being carried out in humans.

Administration, Inhalation↗
PubMed2000

Hepatic damage caused by chronic arsenic toxicity in experimental animals.

OBJECTIVE: Noncirrhotic fibrosis of the liver is common in subjects chronically consuming ground water geologically contaminated with arsenic, but the mechanism of the hepatic fibrosis is not known. Because lipid peroxidation has been implicated in the development of several other forms of hepatic fibrosis, including iron and copper overload, we have explored the roles of oxidative stress and lipid peroxidation in the causation of hepatic fibrosis in a murine model of chronic arsenic toxicity. METHODS: Male BALB/c mice were given drinking water contaminated with arsenic (3.2 mg/L) or arsenic-free (<0.01 mg/L, control) ad libitum. Mice were sacrificed at 3, 6, 9, 12, and 15 months for examination of hepatic histology and assays of hepatic reduced glutathione content, lipid peroxidation, enzymes of the antioxidant defense system, and membrane-bound sodium/potassium ATPase (Na+/K+ ATPase). RESULTS: After 12 months of arsenic feeding, the liver weights increased significantly as did serum aspartate aminotransferase and alanine aminotransferase. After 6 months of arsenic feeding, hepatic glutathione and the enzymes glucose-6-phosphate dehydrogenase and glutathione peroxidase were significantly lower than those of the control group. Hepatic catalase activity was significantly reduced at 9 months in the arsenic-fed group, while glutathione-S-transferase and glutathione reductase activities were also significantly reduced at 12 and 15 months. Plasma membrane Na+/K+ ATPase activity was reduced after 6 months while lipid peroxidation increased significantly after 6 months of arsenic feeding. Liver histology remained normal for the first 9 months, but showed fatty infiltration after 12 months of arsenic feeding. Histologic evidence of fibrosis was observed after 15 months. CONCLUSION: We have demonstrated hepatic fibrosis due to long-term arsenic toxicity in an animal model. Initial biochemical evidence of hepatic membrane damage, probably due to reduction of glutathione and antioxidant enzymes, may be seen by 6 months. Continued arsenic feeding resulted in fatty liver with serum aminotransferase and alanine aminotransferase elevated at 12 months and hepatic fibrosis at 15 months. The murine model is proposed as relevant to epidemic human toxicity in areas of arsenic contamination.

Alanine Transaminase↗
PubMed2001

Stress-related gene expression in mice treated with inorganic arsenicals.

Arsenic (As) is an environmental chemical of high concern for human health. Acute toxicity of arsenic is dependent on its chemical forms and proximity to high local arsenic concentrations is one of the mechanisms for cell death. This study was designed to define acute arsenic-induced stress-related gene expression in vivo. Mice were injected sc with either sodium arsenite [As(III), 100 micromol/kg], sodium arsenate [As(V), 300 micromol/kg], or saline. To examine stress-related gene expression, livers were removed 3 h after arsenic injection for RNA and protein extraction. The Atlas Mouse Stress/Toxicology array revealed that the expression of genes related to stress, DNA damage, and metabolism was altered by acute arsenic treatments. Expression of heme oxygenase 1 (HO-1), a hallmark for arsenic-induced stress, was increased 10-fold, along with increases in heat shock protein-60 (HSP60), DNA damage inducible protein GADD45, and the DNA excision repair protein ERCC1. Downregulation of certain cytochrome P450 enzymes occurred with arsenic treatment. Multiprobe RNase protection assay revealed the activation of the c-Jun/AP-1 transcription complex after arsenic treatments. Western blot analysis further confirmed the enhanced production of arsenic-induced stress proteins such as HO-1, HSP70, HSP90, metallothionein, the metal-responsive transcription factor MTF-1, nuclear factor kappa B and c-Jun/AP-1. Increases in caspase-1 and cytokines such as tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 were also evident. In summary, this study profiled the gene expression pattern in mice treated with inorganic arsenicals, which adds to our understanding of acute arsenic poisoning and toxicity.

Animals↗
PubMed2002

Measurement of arsenic bioavailability in soil using a primate model.

Several studies have shown limited absorption of arsenic from soils. This has led to increased interest in including measurements of arsenic relative bioavailability from soils in the calculation of risks to human health posed by arsenic-contaminated sites. Most of the information in the literature regarding arsenic bioavailability from soils comes from studies of mining and smelter sites in the western United States. It is unclear whether these observations are relevant to other types of arsenic-contaminated sites. In order to obtain information regarding arsenic bioavailability for other types of sites, relative bioavailability of arsenic from selected soil samples was measured in a primate model. Sodium arsenate was administered to five male Cebus apella monkeys by the intravenous and oral routes, and blood, urine, and feces were collected. Pharmacokinetic behavior of arsenic after intravenous administration and the fractions of dose excreted in urine and feces after both intravenous and oral doses were consistent with previous observations in humans. Soil samples from five waste sites in Florida (one from an electrical substation, one from a wood preservative treatment site, two from pesticide sites, and one from a cattle-dip vat site) were dried and sieved. Soil doses were prepared from these samples and administered orally to the monkeys. Relative bioavailability was assessed based on urinary excretion of arsenic following the soil dose compared with excretion following an oral dose of arsenic in solution. Differences in bioavailability were observed for different sites, with relative bioavailability ranging from 10.7 +/- 4.9% (mean +/- standard deviation) to 24.7 +/- 3.2% for the five soil samples. These observations, coupled with data in the literature, suggest limited oral bioavailability of arsenic in soils from a variety of types of arsenic-contaminated sites.

Administration, Oral↗
PubMed2004

In vivo percutaneous absorption of arsenic from water and CCA-treated wood residue.

This study was conducted to evaluate the dermal absorption of arsenic from residues present on the surface of wood preserved with chromated copper arsenate (CCA). The research reported herein used methods parallel to those of earlier research on the dermal absorption of radiolabeled arsenic (R. C. Wester et al., 1993, Fund. Appl. Toxicol. 20, 336-340), with modifications to allow use of environmental matrices that are not radiolabeled. These modifications include the surface area of application and dietary intake of arsenic, thus maximizing the potential for detection of dermally absorbed arsenic in exposed animals above diet-associated background levels of exposure. Two forms of arsenic were administered in this work. The first, arsenic in solution, was applied to the skin of monkeys to calibrate the model against prior absorption research and to serve as the basis of comparison for absorption of arsenic from CCA-treated wood residues. The second substrate was residue that resides on the surface of CCA-treated wood. Results from this research indicate that this study methodology can be used to evaluate dermally absorbed arsenic without the use of a radiolabel. Urinary excretion of arsenic above background levels can be measured following application of soluble arsenic, and absorption rates (0.6-4.4% absorption) are consistent with prior research using the more sensitive, radiolabeled technique. Additionally, the results show that arsenic is poorly absorbed from CCA-treated wood residues (i.e., does not result in urinary arsenic excretion above background levels).

Administration, Topical↗
PubMed1989

Relation of arsenic exposure to lung cancer among tin miners in Yunnan Province, China.

The relation of mining and smelting exposure to arsenic and lung cancer was studied among tin miners in Yunnan Province in the People's Republic of China. Interviews were conducted in 1985 with 107 living tin miners who had lung cancer and an equal number of age matched controls from among tin miners without lung cancer to obtain information on risk factors for lung cancer including detailed history of employment and tobacco use. Occupational history was combined with industrial hygiene data to estimate cumulative arsenic exposure. Similar methods were also used to estimate radon exposure for simultaneous evaluation in this analysis. The results indicate that subjects in the highest quarter of cumulative arsenic exposure have a relative risk of 22.6 compared with subjects without exposure after adjusting for tobacco and radon exposure, and a positive dose response relation was observed. Simultaneous evaluation of arsenic and tobacco exposure indicates a greater risk for arsenic, whereas simultaneous assessment of arsenic and radon exposure suggests radon to be the greater risk. There is no evidence of synergism between arsenic and tobacco exposure. Among arsenic exposed individuals, cases of lung cancer have longer duration but lower average intensity of arsenic exposure than controls, indicating that duration of exposure to arsenic may be more important than intensity in the aetiology of lung cancer. Finally, risk of lung cancer among workers exposed to arsenic only in mining is only slightly less than for miners whose exposure to arsenic was limited to smelting, although risks are highest when workers were exposed to both mining and smelting.

Adult↗
PubMed2001

Association of blood arsenic levels with increased reactive oxidants and decreased antioxidant capacity in a human population of northeastern Taiwan.

Arsenic is a notorious environmental toxicant known as both a carcinogen and an atherogen in human beings, but the pathogenic mechanisms are not completely understood. In cell culture studies, trivalent arsenic enhanced oxidative stress in a variety of mammalian cells, and this association may be closely associated with the development of arsenic-related diseases. To investigate the effect of arsenic exposure on oxidative stress in humans, we conducted a population study to determine the relationships of blood arsenic to reactive oxidants and antioxidant capacity at the individual level. We recruited 64 study subjects ages 42-75 years from residents of the Lanyang Basin on the northeast coast of Taiwan, where arsenic content in well water varies from 0 to > or = 3,000 microg/L. We used a chemiluminescence method, with lucigenin as an amplifier for measuring superoxide, to measure the plasma level of reactive oxidants. We used the azino-diethyl-benzthiazoline sulphate method to determine the antioxidant capacity level in plasma of each study subject. We determined arsenic concentration in whole blood by hydride formation with an atomic absorption spectrophotometer. The average arsenic concentration in whole blood of study subjects was 9.60 +/- 9.96 microg/L (+/- SD) with a range from 0 to 46.50 microg/L. The level of arsenic concentration in whole blood of study subjects showed a positive association with the level of reactive oxidants in plasma (r = +0.41, p = 0.001) and an inverse relationship with the level of plasma antioxidant capacity (r = -0.30, p = 0.014). However, we found no significant association (p = 0.266) between levels of plasma reactive oxidants and antioxidant capacity. Our results also show that the lower the primary arsenic methylation capability, the lower the level of plasma antioxidant capacity (p = 0.029). These results suggest that ingestion of arsenic-contaminated well water may cause deleterious effects by increasing the level of reactive oxidants and decreasing the level of antioxidant capacity in plasma of individuals. Persistent oxidative stress in peripheral blood may be a mechanism underlying the carcinogenesis and atherosclerosis induced by long-term arsenic exposure.

Adult↗
PubMed2003

Gene expression of inflammatory molecules in circulating lymphocytes from arsenic-exposed human subjects.

Long-term arsenic exposure is associated with an increased risk of vascular diseases including ischemic heart disease, cerebrovascular disease, and carotid atherosclerosis. The pathogenic mechanisms of arsenic atherogenicity are not completely clear. A fundamental role for inflammation in atherosclerosis and its complications has become appreciated recently. To investigate molecular targets of inflammatory pathway possibly involved in arsenic-associated atherosclerosis, we conducted an exploratory study using cDNA microarray and enzyme-linked immunosorbent assay to identify genes with differential expression in arsenic-exposed yet apparently healthy individuals. As an initial experiment, array hybridization was performed with mRNA isolated from activated lymphocytes of 24 study subjects with low (0-4.32 microg/L), intermediate (4.64-9.00 microg/L), and high (9.60-46.5 microg/L) levels of blood arsenic, with each group comprising eight age-, sex-, and smoking frequency-matched individuals. A total of 708 transcripts of known human genes were analyzed, and 62 transcripts (8.8%) showed significant differences in the intermediate or high-arsenic groups compared with the low-level arsenic group. Among the significantly altered genes, several cytokines and growth factors involving inflammation, including interleukin-1 beta, interleukin-6, chemokine C-C motif ligand 2/monocyte chemotactic protein-1 (CCL2/MCP1), chemokine C-X-C motif ligand 1/growth-related oncogene alpha, chemokine C-X-C motif ligand 2/growth-related oncogene beta, CD14 antigen, and matrix metalloproteinase 1 (interstitial collagenase) were upregulated in persons with increased arsenic exposure. Multivariate analyses on 64 study subjects of varying arsenic exposure levels showed that the association of CCL2/MCP1 plasma protein level with blood arsenic remained significant after adjustment for other risk factors of cardiovascular diseases. The results of this gene expression study indicate that the expression of inflammatory molecules may be increased in human subjects after prolonged exposure to arsenic, which might be a contributory factor to the high risk of atherosclerosis in arseniasis-endemic areas in Taiwan. Further multidisciplinary studies, including molecular epidemiologic investigations, are needed to elucidate the role of arsenic-associated inflammation in the development of atherosclerosis and subsequent cardiovascular disease.

Arsenic↗
PubMed1981

The carcinogenicity of arsenic.

A carcinogenic role of inorganic arsenic has been suspected for nearly a century. Exposure to inorganic arsenic compounds occurs in some occupational groups, e.g., among smelter workers and workers engaged in the production and use of arsenic containing pesticides. Substantial exposure can also result from drinking water in certain areas and the use of some drugs. Tobacco and wine have had high As concentrations due to the use of arsenic containing pesticides. Inorganic arsenic compounds interfere with DNA repair mechanisms and an increased frequency of chromosomal aberrations have been observed among exposed workers and patients. Epidemiological data show that inorganic arsenic exposure can cause cancer of the lung and skin. The evidence of an etiologic role of arsenic for angiosarcoma of the liver is highly suggestive; however, the association between arsenic and cancer of other sites needs further investigation. No epidemiological data are available on exposure to organic arsenic compounds and cancer. Animal carcinogenicity studies involving exposure to various inorganic and organic arsenic compounds by different routes have been negative, with the possible exception of some preliminary data regarding lung cancer and leukemia. Some studies have indicated an increased mortality from lung cancer in populations living near point emission sources of arsenic into the air. The role of arsenic cannot be evaluated due to lack of exposure data. Epidemiological data suggest that the present WHO standard for drinking water (50 micrograms As/l.) provides only a small safety margin with regard to skin cancer.

Air Pollutants↗
PubMed2006

Global gene expression associated with hepatocarcinogenesis in adult male mice induced by in utero arsenic exposure.

Our previous work has shown that exposure to inorganic arsenic in utero produces hepatocellular carcinoma (HCC) in adult male mice. To explore further the molecular mechanisms of transplacental arsenic hepatocarcinogenesis, we conducted a second arsenic transplacental carcinogenesis study and used a genomewide microarray to profile arsenic-induced aberrant gene expression more extensively. Briefly, pregnant C3H mice were given drinking water containing 85 ppm arsenic as sodium arsenite or unaltered water from days 8 to 18 of gestation. The incidence of HCC in adult male offspring was increased 4-fold and tumor multiplicity 3-fold after transplacental arsenic exposure. Samples of normal liver and liver tumors were taken at autopsy for genomic analysis. Arsenic exposure in utero resulted in significant alterations (p < 0.001) in the expression of 2,010 genes in arsenic-exposed liver samples and in the expression of 2,540 genes in arsenic-induced HCC. Ingenuity Pathway Analysis revealed that significant alterations in gene expression occurred in a number of biological networks, and Myc plays a critical role in one of the primary networks. Real-time reverse transcriptase-polymerase chain reaction and Western blot analysis of selected genes/proteins showed > 90% concordance. Arsenic-altered gene expression included activation of oncogenes and HCC biomarkers, and increased expression of cell proliferation-related genes, stress proteins, and insulin-like growth factors and genes involved in cell-cell communications. Liver feminization was evidenced by increased expression of estrogen-linked genes and altered expression of genes that encode gender-related metabolic enzymes. These novel findings are in agreement with the biology and histology of arsenic-induced HCC, thereby indicating that multiple genetic events are associated with transplacental arsenic hepatocarcinogenesis.

Animals↗