Arsenolipids in Plankton from High- and Low-Nutrient Oceanic Waters Along a Transect in the North Atlantic.

Although the natural occurrence of arsenic-containing lipids (arsenolipids) in marine organisms is now well established, the possible role of these unusual compounds in organisms and in the cycling of arsenic in marine systems remains largely unexplored. We report the finding of arsenolipids in 61 plankton samples collected from surface marine waters of high- and low-nutrient content along a transect spanning the Gulf Stream in the North Atlantic Ocean. Using high-performance liquid chromatography (HPLC) coupled to both elemental and molecular mass spectrometry, we show that all 61 plankton samples contained six identifiable arsenolipids, namely, three arsenosugar phospholipids (AsPL958, 10-13%; AsPL978, 13-25%; and AsPL1006, 7-10% of total arsenolipids), two arsenic-containing hydrocarbons (AsHC332, 4-10% and AsHC360, 1-2%), and a methoxy-sugar arsenolipid that contained phytol (AsSugPhytol, 1-3%). The relative amounts of the six arsenolipids showed clear dependence on the nutrient status of the ambient water with plankton collected from high-nutrient waters having less of the arsenosugar phospholipids and more of the three non-P containing arsenolipids compared to low-nutrient waters. By combining these first field data of arsenolipids in plankton with reported global phytoplankton productivity, we estimate that the oceans' phytoplankton transform per year 50 000-100 000 tons of arsenic into arsenolipids.

Correction to: Low-moderate arsenic exposure and respiratory health in American Indian communities in the Strong Heart Study.

The original version of this article [1], published on 28 November 2019, contained incorrect title. In this Correction the affected part of the article is shown.

Rice Consumption and Subclinical Lung Disease in US Adults: Observational Evidence From the Multi-Ethnic Study of Atherosclerosis.

Rice accumulates arsenic, an established lung toxicant. Little is known about the association of rice consumption with arsenic-related health effects, particularly interstitial lung disease. Between 2000 and 2002, 6,814 white, black, Hispanic, and Chinese adults from 6 US cities were enrolled in the Multi-Ethnic Study of Atherosclerosis. We included 2,250 participants who had spirometry data, 2,557 with full-lung computed tomography (CT) scans, and 5,710 with cardiac CT scans. Rice consumption and 310 participants with urinary arsenic were assessed at baseline. Spirometry and full-lung CT-derived measures of total lung capacity and high attenuation area (HAA), and interstitial lung abnormalities were measured at examination 5. Cardiac CT-derived HAA was measured at 1-3 visits. Twelve percent of participants reported eating at least 1 serving of rice daily. Comparing data between that group with those who ate less than 1 serving weekly, the mean difference for forced vital capacity was -102 (95% confidence interval (CI): -198, -7) mL, and for forced expiratory volume in 1 second was -90 (95% CI: -170, -11) mL after adjustment for demographics, anthropometrics, dietary factors, and smoking. The cross-sectional adjusted percent difference for total lung capacity was -1.33% (95% CI: -4.29, 1.72) and for cardiac-based HAA was 3.66% (95% CI: 1.22, 6.15). Sensitivity analyses for urinary arsenic were consistent with rice findings. Daily rice consumption was associated with reduced lung function and greater cardiac-based HAA.

Dietary determinants of inorganic arsenic exposure in the Strong Heart Family Study.

BACKGROUND: Chronic exposure to inorganic arsenic (iAs) in the US occurs mainly through drinking water and diet. Although American Indian (AI) populations have elevated urinary arsenic concentrations compared to the general US population, dietary sources of arsenic exposure in AI populations are not well characterized. METHODS: We evaluated food frequency questionnaires to determine the major dietary sources of urinary arsenic concentrations (measured as the sum of arsenite, arsenate, monomethylarsonate, and dimethylarsinate, ΣAs) for 1727 AI participants in the Strong Heart Family Study (SHFS). We compared geometric mean ratios (GMRs) of urinary ΣAs for an interquartile range (IQR) increase in reported food group consumption. Exploratory analyses were stratified by gender and study center. RESULTS: In fully adjusted generalized estimating equation models, the percent increase (95% confidence interval) of urinary ΣAs per increase in reported food consumption corresponding to the IQR was 13% (5%, 21%) for organ meat, 8% (4%, 13%) for rice, 7% (2%, 13%) for processed meat, and 4% (1%, 7%) for non-alcoholic drinks. In analyses stratified by study center, the association with organ meat was only observed in North/South Dakota. Consumption of red meat [percent increase -7% (-11%, -3%)] and fries and chips [-6% (-10%, -2%)] was inversely associated with urinary ΣAs. CONCLUSIONS: Organ meat, processed meat, rice, and non-alcoholic drinks contribute to ΣAs exposure in the SHFS population. Organ meat is a unique source of ΣAs exposure for North and South Dakota participants and may reflect local food consumption. Further studies should comprehensively evaluate drinking water arsenic in SHFS communities and determine the relative contribution of diet and drinking water to total arsenic exposure.

Low-moderate arsenic exposure and respiratory in American Indian communities in the Strong Heart Study.

BACKGROUND: Arsenic exposure through drinking water is an established lung carcinogen. Evidence on non-malignant lung outcomes is less conclusive and suggests arsenic is associated with lower lung function. Studies examining low-moderate arsenic (< 50 µg/L), the level relevant for most populations, are limited. We evaluated the association of arsenic exposure with respiratory health in American Indians from the Northern Plains, the Southern Plains and the Southwest United States, communities with environmental exposure to inorganic arsenic through drinking water. METHODS: The Strong Heart Study is a prospective study of American Indian adults. This analysis used urinary arsenic measurements at baseline (1989-1991) and spirometry at Visit 2 (1993-1995) from 2132 participants to evaluate associations of arsenic exposure with airflow obstruction, restrictive pattern, self-reported respiratory disease, and symptoms. RESULTS: Airflow obstruction was present in 21.5% and restrictive pattern was present in 14.4%. The odds ratio (95% confidence interval) for obstruction and restrictive patterns, based on the fixed ratio definition, comparing the 75th to 25th percentile of arsenic, was 1.17 (0.99, 1.38) and 1.27 (1.01, 1.60), respectively, after adjustments, and 1.28 (1.02, 1.60) and 1.33 (0.90, 1.50), respectively, based on the lower limit of normal definition. Arsenic was associated with lower percent predicted FEV1 and FVC, self-reported emphysema and stopping for breath. CONCLUSION: Low-moderate arsenic exposure was positively associated with restrictive pattern, airflow obstruction, lower lung function, self-reported emphysema and stopping for breath, independent of smoking and other lung disease risk factors. Findings suggest that low-moderate arsenic exposure may contribute to restrictive lung disease.

The Association of Arsenic Exposure and Arsenic Metabolism With the Metabolic Syndrome and Its Individual Components: Prospective Evidence From the Strong Heart Family Study.

Inorganic arsenic exposure is ubiquitous, and both exposure and interindividual differences in its metabolism have been associated with cardiometabolic risk. However, the associations of arsenic exposure and arsenic metabolism with the metabolic syndrome (MetS) and its individual components are relatively unknown. We used Poisson regression with robust variance to evaluate the associations of baseline arsenic exposure (urinary arsenic levels) and metabolism (relative percentage of arsenic species over their sum) with incident MetS and its individual components (elevated waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, hypertension, and elevated fasting plasma glucose) in 1,047 participants from the Strong Heart Family Study, a prospective family-based cohort study in American Indian communities (baseline visits were held in 1998-1999 and 2001-2003, follow-up visits in 2001-2003 and 2006-2009). Over the course of follow-up, 32% of participants developed MetS. An interquartile-range increase in arsenic exposure was associated with a 1.19-fold (95% confidence interval: 1.01, 1.41) greater risk of elevated fasting plasma glucose concentration but not with other individual components of the MetS or MetS overall. Arsenic metabolism, specifically lower percentage of monomethylarsonic acid and higher percentage of dimethylarsinic acid, was associated with higher risk of overall MetS and elevated waist circumference but not with any other MetS component. These findings support the hypothesis that there are contrasting and independent associations of arsenic exposure and arsenic metabolism with metabolic outcomes which may contribute to overall diabetes risk.

Arsenic-gene interactions and beta-cell function in the Strong Heart Family Study.

We explored arsenic-gene interactions influencing pancreatic beta-cell activity in the Strong Heart Family Study (SHFS). We considered 42 variants selected for associations with either beta-cell function (31 variants) or arsenic metabolism (11 variants) in the SHFS. Beta-cell function was calculated as homeostatic model - beta corrected for insulin resistance (cHOMA-B) by regressing homeostatic model - insulin resistance (HOMA-IR) on HOMA-B and adding mean HOMA-B. Arsenic exposure was dichotomized at the median of the sum of creatinine-corrected inorganic and organic arsenic species measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS). Additive GxE models for cHOMA-B were adjusted for age and ancestry, and accounted for family relationships. Models were stratified by center (Arizona, Oklahoma, North Dakota and South Dakota) and meta-analyzed. The two interactions between higher vs. lower arsenic and SNPs for cHOMA-B that were nominally significant at P < 0.05 were with rs10738708 (SNP overall effect -3.91, P = 0.56; interaction effect with arsenic -31.14, P = 0.02) and rs4607517 (SNP overall effect +16.61, P = 0.03; interaction effect with arsenic +27.02, P = 0.03). The corresponding genes GCK and TUSC1 suggest oxidative stress and apoptosis as possible mechanisms for arsenic impacts on beta-cell function. No interactions were Bonferroni-significant (1.16 × 10-3). Our findings are suggestive of oligogenic moderation of arsenic impacts on pancreatic ß-cell endocrine function, but were not Bonferroni-significant.

Dose and Diet - Sources of Arsenic Intake in Mouse in Utero Exposure Scenarios.

In humans, early life exposure to inorganic arsenic is associated with adverse health effects. Inorganic arsenic in utero or in early postnatal life also produces adverse health effects in offspring of pregnant mice that consumed drinking water containing low part per billion levels of inorganic arsenic. Because aggregate exposure of pregnant mice to inorganic arsenic from both drinking water and food has not been fully evaluated in experimental studies, quantifying arsenic exposure of the developing mouse is problematic. Here, we determined levels of total arsenic and arsenic species in natural ingredient rodent diets that are composed of many plant and animal-derived foodstuffs and in a purified ingredient rodent diet that is composed of a more restricted mixture of foodstuffs. In natural ingredient diets, total arsenic levels ranged from ∼60 to ∼400 parts per billion, and in the purified ingredient diet, total arsenic level was 13 parts per billion. Inorganic arsenic was the predominant arsenic species in trifluoroacetic acid extracts of each diet. Various exposure scenarios were evaluated using information on inorganic arsenic levels in diet and drinking water and on daily food and water consumption of pregnant mice. In a scenario in which pregnant mice consumed drinking water with 10 parts per billion of inorganic arsenic and a natural ingredient diet containing 89 parts per billion of inorganic arsenic, drinking water contributed only ∼20% of inorganic arsenic intake. Quantitation of arsenic species in diets used in studies in which drinking water is the nominal source of arsenic exposure provides more accurate dosimetry and improves understanding of dose-response relations. Use of purified ingredient diets will minimize the discrepancy between the target dosage level and the actual dosage level attained in utero exposure studies designed to evaluate effects of low level exposure to inorganic arsenic.

Arsenobetaine in Seawater: Depth Profiles from Selected Sites in the North Atlantic.

Arsenic occurs in marine waters, typically at concentrations of 1-2 µg As kg-1, primarily as the inorganic species arsenate. Marine animals, however, contain extremely high levels of arsenic (typically 2000-20 000 µg As kg-1 wet mass), most of which is present as arsenobetaine, an organic form of arsenic that has never been found in seawater. We report a method based on ion-exchange preconcentration and HPLC/mass spectrometry to measure arsenobetaine in seawater, and apply the method to samples of seawater collected at various depths from seven sites in the North Atlantic. Arsenobetaine was detected in most samples at levels ranging from 0.5 to 10 ng As kg-1, and was found at depths down to 4900 m. Furthermore, we report the presence of 15 additional organoarsenicals in seawater, 14 of which had never been detected in marine waters. The arsenobetaine depth profile was related, albeit weakly, to that of chlorophyll; this relationship probably reflects arsenobetaine's release to water from marine animals associated with the euphotic zone rather than its direct biosynthesis by primary producers. Future application of the new method for seawater analysis will shed new light on the biogeochemical cycle of marine arsenic.

Urinary tungsten and incident cardiovascular disease in the Strong Heart Study: An interaction with urinary molybdenum.

BACKGROUND: Tungsten (W) interferes with molybdenum (Mo) binding sites and has been associated with prevalent cardiovascular disease (CVD). We evaluated if (1) W exposure is prospectively associated with incident CVD and (2) the association between urinary W levels and incident CVD is modified by urinary Mo levels. METHODS: We estimated multi-adjusted hazard ratios (HRs) for incident CVD outcomes by increasing W levels for 2726 American Indian participants in the Strong Heart Study with urinary metal levels measured at baseline (1989-1991) and CVD events ascertained through 2008. RESULTS: Increasing levels of baseline urinary W were not associated with incident CVD. Fully-adjusted HRs (95% CIs) of incident CVD comparing a change in the IQR of W levels for those in the lowest and highest tertile of urinary Mo were 1.05 (0.90, 1.22) and 0.80 (0.70, 0.92), respectively (p-interaction = 0.02); for CVD mortality, the corresponding HRs were 1.05 (0.82, 1.33) and 0.73 (0.58, 0.93), respectively (p-interaction = 0.03). CONCLUSIONS: The association between W and CVD incidence and mortality was positive although non-significant at lower urinary Mo levels and significant and inverse at higher urinary Mo levels. Although prior cross-sectional epidemiologic studies in the general US population found positive associations between urinary tungsten and prevalent cardiovascular disease, our prospective analysis in the Strong Heart Study indicates this association may be modified by molybdenum exposure.

Quantification of acyclovir in dermal interstitial fluid and human serum by ultra-high-performance liquid-high-resolution tandem mass spectrometry for topical bioequivalence evaluation.

Time-concentration curves for the topical anti-viral drug acyclovir can provide valuable information for drug development. Open flow microperfusion is used for continuous sampling of dermal interstitial fluid but it requires validated methods for subsequent sample analysis. Therefore, we developed a sensitive, selective and high-throughput ultra-high-performance liquid chromatography-high-resolution tandem mass spectrometry method to determine acyclovir in human dermal interstitial fluid and serum. We validated the method over a concentration range of 0.1-25 ng/mL for a sample volume of just 20 µL and employed cation-exchange solid-phase extraction in a fully automated sample treatment procedure. Short- and long-term sample stability data and the analysis of 5000 samples from a clinical trial demonstrate the successful application of our method.

Quantifying Inorganic Arsenic and Other Water-Soluble Arsenic Species in Human Milk by HPLC/ICPMS.

Because the toxicity of arsenic depends on its chemical form, risk assessments of arsenic exposure must consider the type of arsenic compound, and hence they require sensitive and robust methods for their determination. Furthermore, the assessment should include studies on the most vulnerable people within a population, such as newborns and infants, and thus there is a need to quantify arsenic species in human milk. Herein we report a method for the determination of arsenic species at low concentrations in human milk by HPLC/ICPMS. Comparison of single and triple quadrupole mass analysers showed comparable performance, although the triple quadrupole instrument more efficiently overcame the problem of ArCl+ interference, from the natural chloride present in milk, without the need for gradient elution HPLC conditions. The method incorporates a protein precipitation step with trifluoroacetic acid followed by addition of dichloromethane or dibromomethane to remove the lipids. The aqueous phase was subjected to anion-exchange and cation-exchange/mixed mode chromatography with aqueous ammonium bicarbonate and pyridine buffer solutions as mobile phases, respectively. For method validation, a human milk sample was spiked with defined amounts of dimethylarsinate, arsenobetaine, and arsenate. The method showed good recoveries (99-103%) with detection limits (in milk) in the range of 10 ng As kg-1. The method was further tested by analyzing two Norwegian human milk samples where arsenobetaine, dimethylarsinate, and a currently unknown As species were found, but iAs was not detected.

Arsenic Methyltransferase is Involved in Arsenosugar Biosynthesis by Providing DMA.

Arsenic is an ubiquitous toxic element in the environment, and organisms have evolved different arsenic detoxification strategies. Studies on arsenic biotransformation mechanisms have mainly focused on arsenate (As(V)) reduction, arsenite (As(III)) oxidation, and arsenic methylation; little is known, however, about the pathway for the biosynthesis of arsenosugars, which are significant arsenic transformation products. Here, the involvement of As(III) S-Adenosylmethionine methyltransferase (ArsM) in arsenosugar synthesis is demonstrated for the first time. Synechocystis sp. PCC 6803 incubated with As(III) or monomethylarsonic acid (MMA(V)) produced dimethylarsinic acid (DMA(V)) and arsenosugars, as determined by high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC/ICPMS). Arsenosugars were also detected in the cells when they were exposed to DMA(V). A mutant strain Synechocystis ΔarsM was constructed by disrupting arsM in Synechocystis sp. PCC 6803. Methylation of arsenic species was not observed in the mutant strain after exposure to arsenite or MMA(V); when Synechocystis ΔarsM was incubated with DMA(V), arsenosugars were detected in the cells. These results suggest that ArsM is a required enzyme for the methylation of inorganic arsenicals, but not required for the synthesis of arsenosugars from DMA, and that DMA is the precursor of arsenosugar biosynthesis. The findings will stimulate more studies on the biosynthesis of complex organoarsenicals, and lead to a better understanding of the bioavailability and function of the organoarsenicals in biological systems.

Chronic arsenic exposure and risk of carotid artery disease: The Strong Heart Study.

BACKGROUND: Inorganic arsenic exposure from naturally contaminated groundwater is related to vascular disease. No prospective studies have evaluated the association between arsenic and carotid atherosclerosis at low-moderate levels. We examined the association of long-term, low-moderate inorganic arsenic exposure with carotid arterial disease. METHODS: American Indians, 45-74 years old, in Arizona, Oklahoma, and North and South Dakota had arsenic concentrations (sum of inorganic and methylated species, µg/g urine creatinine) measured from baseline urine samples (1989-1991). Carotid artery ultrasound was performed in 1998-1999. Vascular disease was assessed by the carotid intima media thickness (CIMT), the presence of atherosclerotic plaque in the carotid, and by the number of segments containing plaque (plaque score). RESULTS: 2402 participants (mean age 55.3 years, 63.1% female, mean body mass index 31.0kg/m2, diabetes 45.7%, hypertension 34.2%) had a median (interquintile range) urine arsenic concentration of 9.2 (5.00, 17.06) µg/g creatinine. The mean CIMT was 0.75mm. 64.7% had carotid artery plaque (3% with >50% stenosis). In fully adjusted models comparing participants in the 80th vs. 20th percentile in arsenic concentrations, the mean difference in CIMT was 0.01 (95% confidence interval (95%CI): 0.00, 0.02) mm, the relative risk of plaque presence was 1.04 (95%CI: 0.99, 1.09), and the geometric mean ratio of plaque score was 1.05 (95%CI: 1.01, 1.09). CONCLUSIONS: Urine arsenic was positively associated with CIMT and increased plaque score later in life although the association was small. The relationship between urinary arsenic and the presence of plaque was not statistically significant when adjusted for other risk factors. Arsenic exposure may play a role in increasing the severity of carotid vascular disease.

Toxicity of two classes of arsenolipids and their water-soluble metabolites in human differentiated neurons.

Arsenolipids are lipid-soluble organoarsenic compounds, mainly occurring in marine organisms, with arsenic-containing hydrocarbons (AsHCs) and arsenic-containing fatty acids (AsFAs) representing two major subgroups. Recently, toxicity studies of several arsenolipids showed a high cytotoxic potential of those arsenolipids in human liver and bladder cells. Furthermore, feeding studies with Drosophila melanogaster indicated an accumulation of arsenolipids in the fruit fly's brain. In this study, the neurotoxic potential of three AsHCs, two AsFAs and three metabolites (dimethylarsinic acid, thio/oxo-dimethylarsenopropanoic acid) was investigated in comparison to the toxic reference arsenite (iAsIII) in fully differentiated human brain cells (LUHMES cells). Thereby, in the case of AsHCs both the cell number and cell viability were reduced in a low micromolar concentration range comparable to iAsIII, while AsFAs and the applied metabolites were less toxic. Mechanistic studies revealed that AsHCs reduced the mitochondrial membrane potential, whereas neither iAsIII nor AsFAs had an impact. Furthermore, neurotoxic mechanisms were investigated by examining the neuronal network. Here, AsHCs massively disturbed the neuronal network and induced apoptotic effects, while iAsIII and AsFAs showed comparatively lesser effects. Taking into account the substantial in vitro neurotoxic potential of the AsHCs and the fact that they could transfer across the physiological barriers of the brain, a neurotoxic potential in vivo for the AsHCs cannot be excluded and needs to be urgently characterized.

A 2-O-Methylriboside Unknown Outside the RNA World Contains Arsenic.

Lipid-soluble arsenic compounds, also called arsenolipids, are ubiquitous marine natural products of currently unknown origin and function. In our search for clues about the possible biological roles of these compounds, we investigated arsenic metabolism in the unicellular green alga Dunaliella tertiolecta, and discovered an arsenolipid fundamentally different from all those previously identified; namely, a phytyl 5-dimethylarsinoyl-2-O-methyl-ribofuranoside. The discovery is of particular interest because 2-O-methylribosides have, until now, only been found in RNA. We briefly discuss the significance of the new lipid in biosynthesis and arsenic biogeochemical cycling.

Estimation of Inorganic Arsenic Exposure in Populations With Frequent Seafood Intake: Evidence From MESA and NHANES.

The sum of urinary inorganic arsenic (iAs) and methylated arsenic (monomethylarsonate and dimethylarsinate (DMA)) species is the main biomarker of iAs exposure. Assessing iAs exposure, however, is difficult in populations with moderate-to-high seafood intakes. In the present study, we used subsamples from the Multi-Ethnic Study of Atherosclerosis (2000-2002) (n = 310) and the 2003-2006 National Health and Nutrition Examination Survey (n = 1,175). We calibrated urinary concentrations of non-seafood-derived iAs, DMA, and methylarsonate, as well as the sum of inorganic and methylated arsenic species, in the Multi-Ethnic Study of Atherosclerosis and of DMA in the National Health and Nutrition Examination Survey by regressing their original concentrations by arsenobetaine and extracting model residuals. To confirm that calibrated biomarkers reflected iAs exposure but not seafood intake, we compared urinary arsenic concentrations by levels of seafood and rice intakes. Self-reported seafood intakes, estimated n-3 polyunsaturated fatty acid levels, and measured n-3 polyunsaturated fatty acid levels were positively associated with the original urinary arsenic biomarkers. Using the calibrated arsenic biomarkers, we found a marked attenuation of the associations with self-reported seafood intake and estimated or measured n-3 fatty acids, whereas associations with self-reported rice intake remained similar. Our residual-based method provides estimates of iAs exposure and metabolism for each participant that no longer reflect seafood intake and can facilitate research about low-to-moderate levels of iAs exposure in populations with high seafood intakes.

Peripheral Arterial Disease and Its Association With Arsenic Exposure and Metabolism in the Strong Heart Study.

At high levels, inorganic arsenic exposure is linked to peripheral arterial disease (PAD) and cardiovascular disease. To our knowledge, no prior study has evaluated the association between low-to-moderate arsenic exposure and incident PAD by ankle brachial index (ABI). We evaluated this relationship in the Strong Heart Study, a large population-based cohort study of American Indian communities. A total of 2,977 and 2,966 PAD-free participants who were aged 45-74 years in 1989-1991 were reexamined in 1993-1995 and 1997-1999, respectively, for incident PAD defined as either ABI <0.9 or ABI >1.4. A total of 286 and 206 incident PAD cases were identified for ABI <0.9 and ABI >1.4, respectively. The sum of inorganic and methylated urinary arsenic species (∑As) at baseline was used as a biomarker of long-term exposure. Comparing the highest tertile of ∑As with the lowest, the adjusted hazard ratios were 0.57 (95% confidence interval (CI): 0.32, 1.01) for ABI <0.9 and 2.24 (95% CI: 1.01, 4.32) for ABI >1.4. Increased arsenic methylation (as percent dimethylarsinate) was associated with a 2-fold increased risk of ABI >1.4 (hazard ratio = 2.04, 95% CI: 1.02, 3.41). Long-term low-to-moderate ∑As and increased arsenic methylation were associated with ABI >1.4 but not with ABI <0.9. Further studies are needed to clarify whether diabetes and enhanced arsenic metabolism increase susceptibility to the vasculotoxic effects of arsenic exposure.

Imaging by Elemental and Molecular Mass Spectrometry Reveals the Uptake of an Arsenolipid in the Brain of Drosophila melanogaster.

Arsenic-containing lipids (arsenolipids) are natural products of marine organisms such as fish, invertebrates, and algae, many of which are important seafoods. A major group of arsenolipids, namely, the arsenic-containing hydrocarbons (AsHC), have recently been shown to be cytotoxic to human liver and bladder cells, a result that has stimulated interest in the chemistry and toxicology of these compounds. In this study, elemental laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) and molecular matrix-assisted laser desorption/ionization (MALDI-)MS were used to image and quantify the uptake of an AsHC in the model organism Drosophila melanogaster. Using these two complementary methods, both an enrichment of arsenic and the presence of the AsHC in the brain were revealed, indicating that the intact arsenolipid had crossed the blood-brain barrier. Simultaneous acquisition of quantitative elemental concentrations and molecular distributions could allow new insight into organ-specific enrichment and possible transportation processes of arsenic-containing bioactive compounds in living organisms.

Metal mixtures in urban and rural populations in the US: The Multi-Ethnic Study of Atherosclerosis and the Strong Heart Study.

BACKGROUND: Natural and anthropogenic sources of metal exposure differ for urban and rural residents. We searched to identify patterns of metal mixtures which could suggest common environmental sources and/or metabolic pathways of different urinary metals, and compared metal-mixtures in two population-based studies from urban/sub-urban and rural/town areas in the US: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Strong Heart Study (SHS). METHODS: We studied a random sample of 308 White, Black, Chinese-American, and Hispanic participants in MESA (2000-2002) and 277 American Indian participants in SHS (1998-2003). We used principal component analysis (PCA), cluster analysis (CA), and linear discriminant analysis (LDA) to evaluate nine urinary metals (antimony [Sb], arsenic [As], cadmium [Cd], lead [Pb], molybdenum [Mo], selenium [Se], tungsten [W], uranium [U] and zinc [Zn]). For arsenic, we used the sum of inorganic and methylated species (∑As). RESULTS: All nine urinary metals were higher in SHS compared to MESA participants. PCA and CA revealed the same patterns in SHS, suggesting 4 distinct principal components (PC) or clusters (∑As-U-W, Pb-Sb, Cd-Zn, Mo-Se). In MESA, CA showed 2 large clusters (∑As-Mo-Sb-U-W, Cd-Pb-Se-Zn), while PCA showed 4 PCs (Sb-U-W, Pb-Se-Zn, Cd-Mo, ∑As). LDA indicated that ∑As, U, W, and Zn were the most discriminant variables distinguishing MESA and SHS participants. CONCLUSIONS: In SHS, the ∑As-U-W cluster and PC might reflect groundwater contamination in rural areas, and the Cd-Zn cluster and PC could reflect common sources from meat products or metabolic interactions. Among the metals assayed, ∑As, U, W and Zn differed the most between MESA and SHS, possibly reflecting disproportionate exposure from drinking water and perhaps food in rural Native communities compared to urban communities around the US.