Selenium-associated differentially expressed microRNAs and their targeted mRNAs across the placental genome in two U.S. birth cohorts.

Selenium is an important micronutrient for foetal development. MicroRNAs play an important role in the function of the placenta, in communication between the placenta and maternal systems, and their expression can be altered through environmental and nutritional cues. To investigate the associations between placental selenium concentration and microRNA expression in the placenta, our observational study included 393 mother-child pairs from the New Hampshire Birth Cohort Study (NHBCS) and the Rhode Island Child Health Study (RICHS). Placental selenium concentrations were quantified using inductively coupled plasma mass spectrometry, and microRNA transcripts were measured using RNA-seq. We fit negative binomial additive models for assessing the association between selenium and microRNAs. We used the microRNA Data Integration Portal (mirDIP) to predict the target mRNAs of the differentially expressed microRNAs and verified the relationships between miRNA and mRNA targets in a subset of samples using existing whole transcriptome data (N = 199). We identified a non-monotonic association between selenium concentration and the expression of miR-216a-5p/miR-217-5p cluster (effective degrees of freedom, EDF = 2.44 and 2.08; FDR = 3.08 × 10-5) in placenta. Thirty putative target mRNAs of miR-216a-5p and/or miR-217-5p were identified computationally and empirically and were enriched in selenium metabolic pathways (driven by selenoprotein coding genes, TXNRD2 and SELENON). Our findings suggest that selenium influences placental microRNA expression. Further, miR-216a-5p and its putative target mRNAs could be the potential mechanistic targets of the health effect of selenium.

Correlates of Manual Therapy and Acupuncture Use Among Rural Patients Seeking Conventional Pain Management: A Cross-sectional Study.

OBJECTIVE: In this cross-sectional study, we examined correlates of manual therapy (spinal manipulation, massage therapy) and/or acupuncture use in a population engaging in conventional pain care in West Virginia. METHODS: Participants were patients (aged 18+ years) from 4 Appalachian pain and rheumatology clinics. Of those eligible (N = 343), 88% completed an anonymous survey including questions regarding health history, pain distress (Short Form Global Pain Scale), prescription medications, and current use of complementary health approaches for pain management. We used age-adjusted logistic regression to assess the relation of sociodemographic, lifestyle, and health-related factors to use of manual therapies and/or acupuncture for pain (complete-case N = 253). RESULTS: The majority of participants were white (92%), female (56%), and middle aged (mean age, 54.8 ± 13.4 years). Nearly all reported current chronic pain (94%), and 56% reported ≥5 comorbidities (mean, 5.6 ± 3.1). Manual therapy and/or acupuncture was used by 26% of participants for pain management (n = 66). Current or prior opioid use was reported by 37% of those using manual therapies. Manual therapy and/or acupuncture use was significantly elevated in those using other complementary health approaches (adjusted odds ratio, 3.0; 95% confidence interval, 1.5-5.8). Overall Short Form Global Pain Scale scores were not significantly associated with use of manual therapies and/or acupuncture after adjustment (adjusted odds ratio per 1-point increase, 1.01; 95% confidence interval, 1.00-1.03). CONCLUSION: We found no evidence for an association of pain-related distress and use of manual therapies and/or acupuncture, but identified a strong association with use of dietary supplements and mind-body therapies. Larger studies are needed to further examine these connections in the context of clinical outcomes and cost-effectiveness in rural adults given their high pain burden and unique challenges in access to care.

Relationship between mercury and selenium concentrations in tissues from stranded odontocetes in the northern Gulf of Mexico.

Odontocetes are apex predators that, despite accumulating mercury (Hg) to high concentrations in their tissues, show few signs of Hg toxicity. One method of Hg detoxification in odontocetes includes the sequestering of Hg in toxicologically inert mercury selenide (HgSe) compounds. To explore the tissue-specific accumulation of Hg and Se and the potential protective role of Se against Hg toxicity, we measured the concentrations of total mercury (THg) and selenium (Se) in multiple tissues from 11 species of odontocetes that stranded along the northern Gulf of Mexico coast [Florida (FL) and Louisiana (LA)]. Tissues were collected primarily from bottlenose dolphins (Tursiops truncatus; n = 93); however, individuals from species in the following 8 genera were also sampled: Feresa (n = 1), Globicephala (n = 1), Grampus (n = 2), Kogia (n = 5), Mesoplodon (n = 1), Peponocephala (n = 4), Stenella (n = 9), and Steno (n = 1). In all species, mean THg concentrations were greatest in the liver and lowest in the blubber, lung, or skin. In contrast, in most species, mean Se concentrations were greatest in the liver, lung, or skin, and lowest in the blubber. For all species combined, Se:Hg molar ratios decreased with increasing THg concentration in the blubber, kidney, liver, lung, and skin following an exponential decay relationship. In bottlenose dolphins, THg concentrations in the kidney, liver, and lung were significantly greater in FL dolphins compared to LA dolphins. On average, in bottlenose dolphins, Se:Hg molar ratios were approximately 1:1 in the liver and >1:1 in blubber, kidney, lung, and skin, suggesting that Se likely protects against Hg toxicity. However, more research is necessary to understand the variation in Hg accumulation within and among species and to assess how Hg, in combination with other environmental stressors, influences odontocete population health.

Selenium-associated DNA methylation modifications in placenta and neurobehavioral development of newborns: An epigenome-wide study of two U.S. birth cohorts.

BACKGROUND/AIM: Selenium (Se) levels in pregnancy have been linked to neurobehavioral development of the offspring. DNA methylation is a potential mechanism underlying the impacts of environmental exposures on fetal development; however, very few studies have been done elucidating the role of DNA methylation linking prenatal Se and child neurobehavior. We aimed to investigate the associations between placental Se concentration and epigenome-wide DNA methylation in two U.S. cohorts, and to assess the association between Se-related DNA methylation modifications and newborns' neurobehavior. METHODS: We measured placental Se concentrations in 343 newborns enrolled in the New Hampshire Birth Cohort Study and in 141 newborns in the Rhode Island Child Health Study. Genome-wide placental DNA methylation was measured by HumanMethylation450 BeadChip, and newborn neurobehavioral development was assessed by the NICU Network Neurobehavioral Scales (NNNS). We meta-analyzed the associations between placental Se concentration and DNA methylation in each cohort, adjusting for covariates. We also fit multiple linear regression and ordinal logistic regression for methylation and newborn NNNS summary scores. RESULTS: We identified five Se-related differentially methylated CpG sites. Among them was cg09674502 (GFI1), where selenium concentration was positively associated with methylation (ß-coefficient = 1.11, FDR-adjusted p-value = 0.045), and where we observed that a one percent methylation level increase was associated with a 15% reduced odds of higher muscle tone in the arms, legs and trunk of newborns, (OR [95% Confidence Interval, CI] = 0.85 [0.77, 0.95]). We also observed for each interquartile range (IQR) increase in selenium concentration in the placenta, there was 1.76 times greater odds of higher hypotonicity (OR [95% CI] = 1.76 [1.12, 2.82]). CONCLUSIONS: Placental selenium concentration was inversely associated with muscle tone of newborns, and hypermethylation of GFI1 could be a potential mechanism underlying this association.

Mercury and selenium concentrations, and selenium:mercury molar ratios in small cetaceans taken off St. Vincent, West Indies.

This study measured the concentration of total mercury (THg) and selenium (Se), and calculated the Se:Hg molar ratios in the muscle, blubber, liver, and kidney of small cetaceans (false killer whale, Pseudorca crassidens; killer whale, Orcinus orca; Risso's dolphin, Grampus griseus; short-finned pilot whale, Globicephala macrorhynchus; and dolphins of the genus Stenella) taken for human consumption off St. Vincent, West Indies. Overall, 122 samples were analyzed; mean THg concentrations (µg/g dry weight) were highest in the liver (730), followed by the kidney (274), muscle (76.4), and blubber (4.57). To explain variability in muscle THg concentrations, carbon (δ13C) and nitrogen (δ15N) stable isotope ratios were analyzed to explore differences in dietary carbon source and relative trophic position, respectively, among species. There was no relationship between δ15N and THg concentration, but there was a positive relationship between δ13C and THg concentration. On average for each species, the Se:Hg molar ratios were >1 in blubber and <1 in muscle. All liver samples and the majority of kidney, muscle, and blubber samples exceeded the FAO/WHO human consumption advisory level of 1 µg/g wet weight. Based on our estimations, consuming only 6.6 g of muscle a week would exceed the MeHg provisional tolerable weekly intake of 1.6 µg MeHg/kg body weight/week for a 60 kg person. Given the high THg concentration in these cetaceans and the frequency at which these tissues are consumed, this is a potential human health issue that warrants further investigation.

Toenail-Based Metal Concentrations and Young-Onset Breast Cancer.

Several metals have carcinogenic properties, but their associations with breast cancer are not established. We studied cadmium, a metalloestrogen, and 9 other metals-arsenic, cobalt, chromium, copper, mercury, molybdenum, lead, tin, and vanadium--in relation to young-onset breast cancer (diagnosis age <50 years), which tends to be more aggressive than and have a different risk profile from later-onset disease. Recent metal exposure was measured by assessing element concentrations, via inductively coupled plasma mass spectrometry, in toenail clippings of 1,217 disease-discordant sister pairs in the US-based Sister (2003-2009) and Two Sister (2008-2010) studies. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. After correcting for differential calendar time of sample collection, no statistically significant associations were observed between any metals and breast cancer. Vanadium had the largest odds ratio (for fourth vs. first quartile, odds ratio = 1.54, 95% confidence interval: 0.75, 3.16; P for trend = 0.21). The association between cadmium and young-onset breast cancer was near null, with no evidence of a dose-response relationship (for fourth vs. first quartile, odds ratio = 0.95, 95% confidence interval: 0.64, 1.43; P for trend = 0.64). Positive associations between urinary cadmium concentrations and breast cancer have been reported in case-control studies, but we observed no such association between young-onset breast cancer and toenail concentrations of any assessed metals.

Maternal exposure to selenium and cadmium, fetal growth, and placental expression of steroidogenic and apoptotic genes.

BACKGROUND: Cadmium (Cd) and selenium (Se) antagonistically influence redox balance and apoptotic signaling, with Cd potentially promoting and Se inhibiting oxidative stress and apoptosis. Alterations to placental redox and apoptotic functions by maternal exposure to Cd and Se during pregnancy may explain some of the Cd and Se associations with fetal development. OBJECTIVES: Investigate associations between Cd and Se concentrations in maternal toenails with placental expression patterns of tumor necrosis factor (TNF) and steroidogenic genes involved in redox reactions and test associations with fetal growth. METHODS: In a sub-sample from the Rhode Island Child Health Study (n = 173), we investigated the relationships between: (1) maternal toenail Cd and Se concentrations and fetal growth using logistic regression, (2) Cd and Se interactions with factor scores from placental TNF and steroidogenic expression patterns (RNAseq) using linear models, and (3) TNF and steroidogenic expression factors with fetal growth via analysis of covariance. RESULTS: Se was associated with decreased odds of intrauterine growth restriction (IUGR) (OR = 0.27, p-value = 0.045). Cd was associated with increased odds of IUGR (OR = 1.95, p-value = 0.13) and small for gestational age (SGA) births (OR = 1.46, p-value = 0.11), though not statistically significant. Cd and Se concentrations were antagonistically associated with placental TNF and steroidogenic expression patterns, which also differed by birth size. CONCLUSIONS: Se may act as an antagonist to Cd and as a modifiable protective factor in fetal growth restriction, and these data suggest these effects may be due to associated variations in the regulation of genes involved in placental redox balance and/or apoptotic signaling.

Spatial differences in trace element bioaccumulation in turtles exposed to a partially remediated coal fly ash spill.

Large-scale releases of environmental contaminants from industrial facilities can cause considerable damage to surrounding ecosystems and require remediation. The expense and/or undesirable environmental side effects of physical removal may constrain remediation efforts. In 2008, approximately 4.1 million m3 of fly ash were released into the Emory River at a coal-burning power plant in Kingston, Tennessee, USA. Approximately 390 000 m3 of fly ash were not removed (hereafter "residual ash"), to avoid disturbing underlying legacy contamination from unrelated historical industrial activity. In 2011 and 2012, the authors measured trace element concentrations in an assemblage of freshwater turtles in 2 rivers impacted by the spill and in a third river that was unaffected. Concentrations of arsenic, copper, iron, mercury, manganese, selenium, and zinc were higher in turtles from rivers affected by the spill but low relative to concentrations known to be toxic to other vertebrates. Concentrations of some trace elements decreased with distance from the original spill site but were not strongly affected by nearby volumes of residual ash. Among-species differences in trace element bioaccumulation and/or the relatively low spatial resolution of available data on residual ash volumes may have obscured this effect. The results suggest that the spill influenced turtle bioaccumulation of trace elements but that distance from the spill site may be a more important factor than residual ash in influencing postremediation bioaccumulation. Environ Toxicol Chem 2017;36:201-211. © 2016 SETAC.

Auricular acupuncture for spinal cord injury related neuropathic pain: a pilot controlled clinical trial.

OBJECTIVE: To obtain preliminary data on the effects of an auricular acupuncture protocol, Battlefield Acupuncture (BFA), on self-reported pain intensity in persons with chronic Spinal Cord Injury (SCI) and neuropathic pain. DESIGN: Pilot randomized delayed entry single center crossover clinical trial at an outpatient rehabilitation and integrative medicine hospital center. METHODS: Chronic (> one year post injury) ASIA impairment scale A through D individuals with SCI with injury level from C3 through T12 and below level neuropathic pain with at least five on the Numeric Rating Scale (NRS) were recruited. Twenty-four subjects were randomized to either an eight-week once weekly ten-needle BFA protocol (n = 13) or to a waiting list followed by the BFA protocol (n = 11). OUTCOME MEASURES: The primary outcome measure was change in the pain severity NRS. Secondary outcome was the Global Impression of Change. RESULTS: Demographically there were no significant differences between groups. Mean pain scores at baseline were higher in acupuncture than control subjects (7.75 ± 1.54 vs. 6.25 ± 1.04, P = 0.027). Although both groups reported significant reduction in pain during the trial period, the BFA group reported more pain reduction than the delayed entry group (average change in NRS at eight weeks -2.92 ± 2.11 vs. -1.13 ± 2.14, P = 0.065). There was a significant difference in groups when a group-by-time interaction in a mixed-effect repeated measures model (P = 0.014). CONCLUSION: This pilot study has provided proof of concept that BFA has clinically meaningful effect on the modulation of SCI neuropathic pain.

Placental Metal Concentrations in Relation to Maternal and Infant Toenails in a U.S. Cohort.

Metal contaminants cross the placenta, presenting a heightened risk of perturbing fetal development. Information about placental concentrations and transfer of multiple potentially toxic metals from low to moderate exposure is lacking. We measured concentrations of Cd, Pb, Hg, Mn, Se, and Zn in 750 placentas collected from women enrolled in the New Hampshire Birth Cohort Study and examined the correlation between elements, and profiles of potentially toxic metals (Cd, Pb, Hg, and Mn) stratified by nutrient concentrations (Zn and Se) using principal components analyses. We further examined the indirect effects of maternal metal concentrations on infant metal concentrations through placental metal concentrations using structural equation models. Placental metal concentrations were all correlated, particularly Zn and Mn, and Zn and Cd, and the principal component of metals differed by stratum of high versus low Zn and Se. Associations were observed between placenta and maternal toenail Se (ß = 63.49; P < 0.0001) and Pb (ß = 0.90; P < 0.0001) but not other metals. Structural equation models did not indicate any statistically significant indirect effects through placental metal concentrations. Placental metal concentrations may represent a distinct biomarker of metal exposure and adverse health impacts to the fetus, particularly those stemming from the placenta.

Is the inverse association between selenium and bladder cancer due to confounding by smoking?

Selenium has been linked to a reduced risk of bladder cancer in some studies. Smoking, a well-established risk factor for bladder cancer, has been associated with lower selenium levels in the body. We investigated the selenium-bladder cancer association in subjects from Maine, New Hampshire, and Vermont in the New England Bladder Cancer Case-Control Study. At interview (2001-2005), participants provided information on a variety of factors, including a comprehensive smoking history, and submitted toenail samples, from which we measured selenium levels. We estimated odds ratios and 95% confidence intervals among 1,058 cases and 1,271 controls using logistic regression. After controlling for smoking, we saw no evidence of an association between selenium levels and bladder cancer (for fourth quartile vs. first quartile, odds ratio (OR) = 0.98, 95% confidence interval (CI): 0.77, 1.25). When results were restricted to regular smokers, there appeared to be an inverse association (OR = 0.76, 95% CI: 0.58, 0.99); however, when pack-years of smoking were considered, this association was attenuated (OR = 0.91, 95% CI: 0.68, 1.20), indicating potential confounding by smoking. Despite some reports of an inverse association between selenium and bladder cancer overall, our results, combined with an in-depth evaluation of other studies, suggested that confounding from smoking intensity or duration could explain this association. Our study highlights the need to carefully evaluate the confounding association of smoking in the selenium-bladder cancer association.

The effects of a remediated fly ash spill and weather conditions on reproductive success and offspring development in tree swallows.

Animals are exposed to natural and anthropogenic stressors during reproduction that may individually or interactively influence reproductive success and offspring development. We examined the effects of weather conditions, exposure to element contamination from a recently remediated fly ash spill, and the interaction between these factors on reproductive success and growth of tree swallows (Tachycineta bicolor) across nine colonies. Females breeding in colonies impacted by the spill transferred greater concentrations of mercury (Hg), selenium (Se), strontium, and thallium to their eggs than females in reference colonies. Parental provisioning of emerging aquatic insects resulted in greater blood Se concentrations in nestlings in impacted colonies compared to reference colonies, and these concentrations remained stable across 2 years. Egg and blood element concentrations were unrelated to reproductive success or nestling condition. Greater rainfall and higher ambient temperatures during incubation were later associated with longer wing lengths in nestlings, particularly in 2011. Higher ambient temperatures and greater Se exposure posthatch were associated with longer wing lengths in 2011 while in 2012, blood Se concentrations were positively related to wing length irrespective of temperature. We found that unseasonably cold weather was associated with reduced hatching and fledging success among all colonies, but there was no interactive effect between element exposure and inclement weather. Given that blood Se concentrations in some nestlings exceeded the lower threshold of concern, and concentrations of Se in blood and Hg in eggs are not yet declining, future studies should continue to monitor exposure and effects on insectivorous wildlife in the area.

Influence of relative trophic position and carbon source on selenium bioaccumulation in turtles from a coal fly-ash spill site.

Selenium (Se) is a bioaccumulative constituent of coal fly-ash that can disrupt reproduction of oviparous wildlife. In food webs, the greatest enrichment of Se occurs at the lowest trophic levels, making it readily bioavailable to higher consumers. However, subsequent enrichment at higher trophic levels is less pronounced, leading to mixed tendencies for Se to biomagnify. We used stable isotopes ((1)(5)N and (13)C) in claws to infer relative trophic positions and relative carbon sources, respectively, of seven turtle species near the site of a recently-remediated coal fly-ash spill. We then tested whether Se concentrations differed with relative trophic position or relative carbon source. We did not observe a strong relationship between δ(15)N and Se concentration. Instead, selenium concentrations decreased with increasing δ(13)C among species. Therefore, in an assemblage of closely-related aquatic vertebrates, relative carbon source was a better predictor of Se bioaccumulation than was relative trophic position.

A review of recent developments in the speciation and location of arsenic and selenium in rice grain.

Rice is a staple food yet is a significant dietary source of inorganic arsenic, a class 1, nonthreshold carcinogen. Establishing the location and speciation of arsenic within the edible rice grain is essential for understanding the risk and for developing effective strategies to reduce grain arsenic concentrations. Conversely, selenium is an essential micronutrient and up to 1 billion people worldwide are selenium-deficient. Several studies have suggested that selenium supplementation can reduce the risk of some cancers, generating substantial interest in biofortifying rice. Knowledge of selenium location and speciation is important, because the anti-cancer effects of selenium depend on its speciation. Germanic acid is an arsenite/silicic acid analogue, and location of germanium may help elucidate the mechanisms of arsenite transport into grain. This review summarises recent discoveries in the location and speciation of arsenic, germanium, and selenium in rice grain using state-of-the-art mass spectrometry and synchrotron techniques, and illustrates both the importance of high-sensitivity and high-resolution techniques and the advantages of combining techniques in an integrated quantitative and spatial approach.

Pancreatic cancer risk and levels of trace elements.

BACKGROUND AND AIMS: Knowledge on the aetiology of exocrine pancreatic cancer (EPC) is scant. The best established risk factor for EPC is tobacco smoking. Among other carcinogens, tobacco contains cadmium, a metal previously associated with an increased risk of EPC. This study evaluated the association between concentrations of trace elements in toenails and EPC risk. METHODS: The study included 118 EPC cases and 399 hospital controls from eastern Spain. Levels of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. OR and 95% CI, adjusted for potential confounders, were calculated using logistic regression. RESULTS: Significantly increased risks of EPC were observed among subjects whose concentrations of cadmium (OR 3.58, 95% CI 1.86 to 6.88; p(trend)=5×10(-6)), arsenic (OR 2.02, 95% CI 1.08 to 3.78; p(trend)=0.009) and lead (OR 6.26, 95% CI 2.71 to 14.47; p(trend)=3×10(-5)) were in the highest quartile. High concentrations of selenium (OR 0.05, 95% CI 0.02 to 0.15; p(trend)=8×10(-11)) and nickel (OR 0.27, 95% CI 0.12 to 0.59; p(trend)=2×10(-4)) were inversely associated with the risk of EPC. CONCLUSION: Novel associations are reported of lead, nickel and selenium toenail concentrations with pancreas cancer risk. Furthermore, the results confirm previous associations with cadmium and arsenic. These novel findings, if replicated in independent studies, would point to an important role of trace elements in pancreatic carcinogenesis.

[Effect of electroacupuncture on expression of spinal neuronal nitric oxide synthase protein and mRNA in rats with neuropathic pain].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on expression of neuronal nitric oxide synthase (nNOS) protein and mRNA in the spinal cord in rats with chronic constrictive injury (CCI) of the sciatic nerve so as to explore its mechanisms underlying pain relief. METHODS: Thirty-six male SD rats were randomly divided into sham operation (control) group (n = 12), CCI model group (n = 12) and EA group (n = 12). EA was applied to bilateral "Weizhong" (BL 40) and "Huan-tiao" (GB 30) on the injured side for 30 min, once a day for 7 days (from the 11th day on after CCI). The mechanical and thermal pain thresholds were measured before and after CCI. Spinal nNOS protein and mRNA expression levels were detected by Western blot and reverse transcription-polymerase chain reaction (RT-PCR), respectively. RESULTS: In comparison with the control group, both mechanical and thermal pain thresholds were significantly lower in the model group (P < 0.01). Compared with the model group, the two types of pain threshold were increased considerably on the 16th day in the EA group (P < 0.01). In comparison with the control group, the spinal nNOS protein and mRNA expression levels were increased significantly in the model group (P < 0.05, P < 0.01). In comparison with the model group, both nNOS protein and mRNA expression levels in the spinal cord were down-regulated obviously in the EA group (P < 0.05). CONCLUSION: Electroacupuncture can alleviate neuropathic pain in CCI rats, which is closely related to its effect in down-regulating the expression of nNOS protein and mRNA in the spinal cord.

Lung cancer in a U.S. population with low to moderate arsenic exposure.

BACKGROUND: Little is known about the carcinogenic potential of arsenic in areas with low to moderate concentrations of arsenic (< 100 microg/L) in drinking water. OBJECTIVES: We examined associations between arsenic and lung cancer. METHODS: A population-based case-control study of primary incident lung cancer was conducted in 10 counties in two U.S. states, New Hampshire and Vermont. The study included 223 lung cancer cases and 238 controls, each of whom provided toenail clippings for arsenic exposure measurement by inductively coupled-plasma mass spectrometry. We estimated odds ratios (ORs) of the association between arsenic exposure and lung cancer using unconditional logistic regression with adjustment for potential confounders (age, sex, race/ethnicity, smoking pack-years, education, body mass index, fish servings per week, and toenail selenium level). RESULTS: Arsenic exposure was associated with small-cell and squamous-cell carcinoma of the lung [OR = 2.75; 95% confidence interval (CI), 1.00-7.57] for toenail arsenic concentration > or = 0.114 microg/g, versus < 0.05 microg/g. A history of lung disease (bronchitis, chronic obstructive pulmonary disease, or fibrosis) was positively associated with lung cancer (OR = 2.86; 95% CI, 1.39-5.91). We also observed an elevated risk of lung cancer among participants with a history of lung disease and toenail arsenic > or = 0.05 microg/g (OR = 4.78; 95% CI, 1.87-12.2) than among individuals with low toenail arsenic and no history of lung disease. CONCLUSION: Although this study supports the possibility of an increased risk of specific lung cancer histologic types at lower levels of arsenic exposure, we recommend large-scale population-based studies.

Selenomethionine biotransformation and incorporation into proteins along a simulated terrestrial food chain.

Selenium is an essential trace element in vertebrates, but there is a narrow concentration range between dietary requirement and toxicity threshold. Although a great deal is known about the biochemistry of Se from a nutritional perspective, considerably less attention has been focused on the specific biochemistry of Se as an environmental toxicant. Recent advances in hyphenated analytical techniques have provided the capability of quantifying specific chemical forms of Se in biological tissues as well as the distribution of Se among macromolecules. We applied liquid chromatography coupled to inductively coupled plasma mass spectrometryto investigate biotransformations of selenomethionine along a simulated terrestrial food chain consisting of selenomethionine exposed crickets (Acheta domesticus) fed to western fence lizards (Sceloporus occidentalis). Evidence was obtained for selenomethionine biotransformation as well as for sex-specific differences in the metabolism of Se compounds and their subsequent incorporation into proteins in the lizard. The results demonstrate the complexities involved in trophic transfer of Se due to the potential for extensive biotransformation and the species- and even sex-specific nature of these biotransformations.

Isolation and partial characterization of proteins involved in maternal transfer of selenium in the western fence lizard (Sceloporus occidentalis).

Selenium from dietary exposure is efficiently transferred from mother to offspring in oviparous vertebrates, where it can cause severe teratogenic effects. We isolated and partially characterized proteins involved in maternal transfer of selenium in the oviparous lizard Sceloporus occidentalis using size-exclusion chromatography, inductively coupled plasma-mass spectrometry, and polyacrylamide gel electrophoresis. Selenium from dietary selenomethionine exposure was incorporated into at least three egg proteins. One of these proteins was lipovitellin. The other two proteins may be part of a previously unknown mechanism of maternal transfer of Se that is independent of vitellogenesis or albumin secretion. Our results suggest at least three pathways for maternal transfer of Se in vertebrates that may vary in importance depending on the species.

Characterzation of colloidal and humic-bound Ni and U in the "dissolved" fraction of contaminated sediment extracts.

The dissolved phase of environmental aqueous samples is generally defined by filtration at 0.2 microm or even 0.45 microm. However, it is also acknowledged that colloids <0.2 microm suspended in the aqueous phase can be important for determining contaminant availability and mobility. We have used flow field-flow fractionation (FI FFF) and size exclusion chromatography (SEC) coupled to UV-absorbance (UVA) and inductively coupled plasma mass spectrometry (ICP-MS) to study the dissolved organic matter (DOM) and colloidal binding of U and Ni in water extracts of sediments collected from a contaminated area of the Savannah River Site, a U.S. Department of Energy former nuclear materials production and processing facility, near Aiken, SC. High-performance SEC-UVA-ICP-MS was well-suited to the separation of DOM overthe molecular weight (MW) range of approximately 200-7000 Da. The ICP-MS element specific data indicated that a significant fraction of U was associated with DOM. Uranium exhibited a bimodal distribution and the other fraction was greater than the exclusion limit for the column and coeluted with Al. Flow FFF was used to size this fraction as colloidal with an approximate effective spherical diameter of 0.09-0.12 microm. Element specific ICP-MS data confirmed that U and Al were associated with the colloidal phase. High-field FI FFF was also applicable to sizing DOM but resolution was poorer than SEC. The results of this study suggest that "dissolved" U at this site is predominantly either complexed by DOM or bound to a colloidal fraction while Ni is predominately present as labile complexes or the free cation and, therefore, potentially bioavailable.