Occupational Lead Exposure Ototoxicity Evaluated With Distortion-Product Otoacoustic Emissions.

OBJECTIVES: To evaluate the extent of hearing loss among pottery workers in Mexico exposed to lead. DESIGN: The authors conducted a cross-sectional study including 315 adult pottery workers. Auditory function was evaluated by air conduction pure-tone audiometry (pure-tone average) and distortion-product otoacoustic emission (DPOAE) levels (amplitude and signal-to-noise ratio). Lead exposure was assessed with a single blood sample test and classified as low, medium, and high according to blood lead tertiles. Logistic regression models were calculated for the association between blood lead levels, pure-tone average, and DPOAE records. RESULTS: Median (25th-75th) blood lead levels were 14 µg/dL (7.5-22.6 µg/dL). The audiometric pattern and DPOAE records were similar across blood lead levels groups in all frequencies, and no statistically significant differences were found. Adjusted logistic regression models showed no increase in the odds for hearing thresholds >25 dB (HL) and DPOAE absence associated with blood lead levels, and no dose-response pattern was observed ( p > 0.05). CONCLUSIONS: Given the results from this cross-sectional study, no association was found between blood lead levels and hearing loss assessed with DPOAE. Future longitudinal work should consider chronic lead exposure estimates among underrepresented populations, which can potentially inform safer work practices to minimize the risk of ototoxicity.

Arsenic and the epigenome: interindividual differences in arsenic metabolism related to distinct patterns of DNA methylation.

Biotransformation of inorganic arsenic (iAs) is one of the factors that determines the character and magnitude of the diverse detrimental health effects associated with chronic iAs exposure, but it is unknown how iAs biotransformation may impact the epigenome. Here, we integrated analyses of genome-wide, gene-specific promoter DNA methylation levels of peripheral blood leukocytes with urinary arsenical concentrations of subjects from a region of Mexico with high levels of iAs in drinking water. These analyses revealed dramatic differences in DNA methylation profiles associated with concentrations of specific urinary metabolites of arsenic (As). The majority of individuals in this study had positive indicators of As-related disease, namely pre-diabetes mellitus or diabetes mellitus (DM). Methylation patterns of genes with known associations with DM were associated with urinary concentrations of specific iAs metabolites. Future studies will determine whether these DNA methylation profiles provide mechanistic insight into the development of iAs-associated disease, predict disease risk, and/or serve as biomarkers of iAs exposure in humans.

Relationship between urinary biomarkers of early kidney damage and exposure to inorganic toxins in a pediatric population of Apizaco, Tlaxcala, Mexico.

BACKGROUND: In recent years, chronic kidney disease has increased in the pediatric population and has been related to environmental factors. In the diagnosis of kidney damage, in addition to the traditional parameters, early kidney damage biomarkers, such as kidney injury molecule 1, cystatin C, and osteopontin, among others, have been implemented as predictors of early pathological processes. OBJECTIVE: This study aimed to evaluate the relationship between exposure to environmental pollutants and early kidney damage biomarkers. METHODS: A cross-sectional pilot study was conducted in February 2016 and involved 115 apparently healthy children aged 6-15 residing in Apizaco, Tlaxcala. Participant selection was carried out randomly from among 16,472 children from the municipality of Apizaco. A socio-demographic questionnaire included  age, sex, education, duration of residence in the area, occupation, water consumption and dietary habits, pathological history, and some non-specific symptoms. Physical examination included blood pressure, weight, and height. The urine concentrations of urinary aluminum, total arsenic, boron, calcium, chromium, copper, mercury, potassium, sodium, magnesium, manganese, molybdenum, lead, selenium, silicon, thallium, vanadium, uranium, and zinc, were measured. Four of the 115 participants selected for the study were excluded due to an incomplete questionnaire or lack of a medical examination, leaving a final sample population of 111 participants. RESULTS: The results showed a mean estimated glomerular filtration rate of 89.1 ± 9.98 mL/min/1.73m2 and a mean albumin/creatinine ratio of 12.9 ± 16.7 mg/g urinary creatinine. We observed a positive and significant correlation between estimated glomerular filtration rate with fluoride, total arsenic and lead, and a correlation of albumin/creatinine ratio with fluoride, vanadium, and total arsenic. There was also a significant correlation between the early kidney damage biomarkers and fluoride, vanadium, and total arsenic, except for cystatin C. CONCLUSION: In conclusion, our results show that four urinary biomarkers: α1-microglobulin, cystatin C, kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin are related to environmental exposure to urinary fluoride, vanadium, and total arsenic in our pediatric population.

Effect of smoking on the redox status of knee osteoarthritis: A preliminary study.

Even though smoking has been scarcely studied in osteoarthritis (OA) etiology, it is considered a controversial risk factor for the disease. Exposure to tobacco smoke has been reported to promote oxidative stress (OS) as part of the damage mechanism. The aim of this study was to assess whether smoking increases cartilage damage through the generation of OS. Peripheral blood (PB) and synovial fluid (SF) samples from patients with OA were analyzed. The samples were stratified according to smoking habit, Kellgren-Lawrence score, pain, and cotinine concentrations in PB. Malondialdehyde (MDA), methylglyoxal (MGO), advanced protein oxidation products (APOPs), and myeloperoxidase (MPO) were assessed; the activity of antioxidant enzymes such as gamma-glutamyl transferase (GGT), glutathione S-transferase (GST) and catalase (CAT), as well as the activity of arginase, which favors the destruction of cartilage, was determined. When stratified by age, for individuals <60 years, the levels of MDA and APOPs and the activity of MPO and GST were higher, as well as antioxidant system activity in the smoking group (OA-S). A greater degree of pain in the OA-S group increased the concentrations of APOPs and arginase activity (P < 0.01 and P < 0.05, respectively). Arginase activity increased significantly with a higher degree of pain (P < 0.01). Active smoking can be an important risk factor for the development of OA by inducing systemic OS in young adults, in addition to reducing antioxidant enzymes in older adults and enhancing the degree of pain and loss of cartilage.

Identification of the GST-T1 and GST-M1 null genotypes using high resolution melting analysis.

Glutathione S-transferases, including GST-T1 and GST-M1, are known to be involved in the phase II detoxification pathways for xenobiotics as well as in the metabolism of endogenous compounds. Polymorphisms in these genes have been linked to an increased susceptibility to carcinogenesis and associated with risk factors that predispose to certain inflammatory diseases. In addition, GST-T1 and GST-M1 null genotypes have been shown to be responsible for interindividual variations in the metabolism of arsenic, a known human carcinogen. To assess the specific GST genotypes in the Mexican population chronically exposed to arsenic, we have developed a multiplex High Resolution Melting PCR (HRM-PCR) analysis using a LightCycler480 instrument. This method is based on analysis of the PCR product melting curve that discriminates PCR products according to their lengths and base sequences. Three pairs of primers that specifically recognize GST-T1, GST-M1, and ß-globin, an internal control, to produce amplicons of different length were designed and combined with LightCycler480 High Resolution Melting Master Mix containing ResoLight, a completely saturating DNA dye. Data collected from melting curve analysis were evaluated using LightCycler480 software to determine specific melting temperatures of individual melting curves representing target genes. Using this newly developed multiplex HRM-PCR analysis, we evaluated GST-T1 and GST-M1 genotypes in 504 DNA samples isolated from the blood of individuals residing in Zimapan, Lagunera, and Chihuahua regions in Mexico. We found that the Zimapan and Lagunera populations have similar GST-T1 and GST-M1 genotype frequencies which differ from those of the Chihuahua population. In addition, 14 individuals have been identified as carriers of the double null genotype, i.e., null genotypes in both GST-T1 and GST-M1 genes. Although this procedure does not distinguish between biallelic (+/+) and monoallelic (+/-) genotypes, it can be used in an automated workflow as a simple, sensitive, and time and money saving procedure for rapid identification of the GST-T1 and GST-M1 positive or null genotypes.

Epigenetic changes in individuals with arsenicosis.

Inorganic arsenic (iAs) is an environmental toxicant currently poisoning millions of people worldwide, and chronically exposed individuals are susceptible to arsenicosis or arsenic poisoning. Using a state-of-the-art technique to map the methylomes of our study subjects, we identified a large interactome of hypermethylated genes that are enriched for their involvement in arsenic-associated diseases, such as cancer, heart disease, and diabetes. Notably, we have uncovered an arsenic-induced tumor suppressorome, a complex of 17 tumor suppressors known to be silenced in human cancers. This finding represents a pivotal clue in unraveling a possible epigenetic mode of arsenic-induced disease.

NADPH oxidase participates in the oxidative damage caused by fluoride in rat spermatozoa. Protective role of α-tocopherol.

Fluorosis, caused by drinking water contaminated with inorganic fluoride, is a public health problem in many areas around the world. The aim of this study was to evaluate oxidative stress in spermatozoa caused by fluoride and NADPH oxidase in relationship to fluoride. Four experimental groups of male Wistar rats were administered with deionized water, NaF, at a dose equivalent to 5 mg fluoride kg⁻¹ per 24 h, NaF plus 20 mg kg⁻¹ per 24 h α-tocopherol, or α-tocopherol alone for 60 days. We evaluated several spermatozoa parameters in the four groups: standard quality analysis, superoxide dismutase (SOD) activity, the generation of reactive oxygen species (ROS), NADPH oxidase activity, TBARS formation, ultrastructural analyses of spermatozoa using transmission electron microscopy and in vitro fertilization (IVF) capacity. After 60 days of treatment, urinary excretion of fluoride was not modified by α-tocopherol. Spermatozoa from fluoride-treated rats exhibited a significant increase in the generation of ROS, accompanied by a significant increase in NADPH oxidase activity. The increase in ROS generation was significantly diminished by diphenylene iodonium, an inhibitor of NADPH oxidase activity. In contrast, a decrease in the generation of ROS, an increase in SOD activity and the prevention of TBARS formation process were observed in spermatozoa of rats exposed to fluoride plus α-tocopherol. Finally, α-tocopherol treatment prevented the IVF incapacity observed in the spermatozoa from fluoride-treated rats. These results suggest that NADPH oxidase participates in the oxidative stress damage caused by subchronic exposure to fluoride.

Tissue levels of arsenicals and skin tumor response following administration of monomethylarsonous acid and arsenite to K6/ODC mice.

The effects of monomethylarsonous acid (MMA[III]) and arsenite, administered in drinking water on tissue levels of arsenicals, cytogenetics, and mouse skin tumorigenicity were determined. A low-methionine diet modified the pattern of arsenical tissue concentrations and decreased the tissue arsenical concentrations, particularly in kidney and urinary bladder, less so in liver, and had little effect in the lungs. In mice given 75 ppm arsenite and a low-methionine diet, the urinary bladder tissue levels were only 29%, 26%, and 38% of the inorganic arsenic (iAs), MMA, and dimethylarsinic acid (DMA) concentrations found in mice eating the control diet. In K6/ODC transgenic mice that consumed a normal diet (Purina 5002), a 26-week drinking water exposure to 10 ppm arsenite resulted in 5% of the treated animals having squamous skin tumors. Exposure to 10, 50, 75, or 150 ppm MMA(III) caused 5%, 6.7%, 5%, or 0% tumor-bearing animals. A low-methionine diet did not markedly change the incidence of skin tumors--10 ppm arsenite led to 10% tumors. With a low-methionine diet, 10 and 50 ppm, MMA(III) caused 5% and 6.7% tumor-bearing animals. In comparing the frequency of tumors in the concurrent control groups (1/70, 1.4%) with the frequency of tumors in the pooled arsenical-treated responsive groups (8/122, 6.6%), there is an excess of 6 mouse skin tumors observed in the pooled arsenical-responsive treatment groups compared to the expected number of tumors based on frequency of tumors observed in concurrent control mice. In summary, studies with MMA(III) and arsenite-treated K6/ODC transgenic mice showed (1) a low-methionine diet substantially altered mouse tissue arsenical levels and (2) numerically elevated incidence of mouse skin tumors following arsenical exposures.

Non-optimal levels of dietary selenomethionine alter splenocyte response and modify oxidative stress markers in female mice.

Many studies evaluating the effects of selenium (Se) status on immunity utilize inorganic Se, although selenomethionine (Se-Met) has been suggested to be more bioavailable and less toxic. In the current study, we investigated the effects of dietary Se-Met on immune system function and cellular redox status in C57BL/6N female mice fed with low (0.02 ppm), sufficient (0.2 ppm, control group), or excess Se-Met (2 ppm) in the diet for 50 days. Low Se-Met intake reduced glutathione peroxidase (GPx) activity and glutathione concentration without modifying lipoperoxidation. While low Se-Met intake also reduced the number of B cells in the spleen, it increased mitogen-induced proliferation, IL-4 and IL-12 secretion when compared to the sufficient Se-Met intake group. In comparison to controls, excess Se-Met intake increased splenocyte proliferation and reduced B cell numbers, IL-4, and IL-12 secretion without affecting oxidative stress markers. These data suggest that Se-Met supplementation should be carefully evaluated as it many influence immune function.

An integrated pharmacokinetic and pharmacodynamic study of arsenite action 2. Heme oxygenase induction in mice.

Heme oxygenase (HO) is the rate-limiting enzyme in heme degradation and its activity has a significant impact on intracellular heme pools. Rat studies indicate that HO induction is a sensitive, dose-dependent response to arsenite (As(III)) exposure in both liver and kidney. The objective of this study was to evaluate the relationship of HO induction to administered As(III) dose, and concentrations of inorganic arsenic (iAs) in tissues and urine. Levels of iAs, mono- (MMA) and dimethylated arsenic (DMA) as well as HO activity were determined in liver, lung and kidney over time in female B6C3F1 mice given a single oral dose of 0, 1, 10, 30 or 100 micromol/kg As(III). Increased HO activity was a time and dose-dependent response in liver and kidney, but not in lung. Activity peaked in the 4-6 h time range in liver and kidney with the responsiveness in liver being approximately 2- to 3-fold greater than kidney. The lowest observed effect levels (LOELs) in this study for HO induction are 30 and 100 micromol/kg, respectively, in liver and kidney. The predominant form of arsenic (As) was iAs in liver at all doses, whereas DMA was the predominant form of As in kidney at all doses. Three- to four-fold higher levels of iAs were achieved in liver compared to kidney. MMA was the least abundant form of As in liver and kidney, never exceeding more than 20% of the total As present. The concentration of iAs in tissue or urine demonstrated the strongest correlation with HO activity in both liver and kidney. Results of this study suggest that HO induction is a biomarker of effect that is specific for tissue iAs because a high, but nontoxic, acute dose of DMA (5220 micromol/kg) did not induce HO in mice. Thus, HO induction has potential for use as a biomarker of effect for inorganic arsenic exposure and may be used as an indicator response to further the development of a biologically-based dose response model for As.

Induction of DNA damage by free radicals generated either by organic or inorganic arsenic (AsIII, MMAIII, and DMAIII) in cultures of B and T lymphocytes.

The aim of this work is based in the premise that inorganic arsenic (AsIII) and trivalentmethylated metabolites monomethylarsonous (MMAIII) and dimethylarsinous (DMAIII) participate in DNA damage through the generation of reactive oxygen species (ROS). We have utilized two lymphoblastic lines, Raji (B cells) and Jurkat (T cells), which were treated with the trivalent arsenic species (dose: 0-100 microM) and analyzed by two assays (comet assay and flow cytometry) in the determination of DNA damage and ROS effects in vivo. The results showed that the damage to the DNA and the generation of ROS are different in both cellular lines with respect to the dose of organic arsenic, and the order of damage is MMAIII>DMAIII>AsIII. This fact suggests that the DMAIII is not always the more cytotoxic intermediary xenobiotic, as has already been reported in another study.

Prenatal Exposure to Sodium Arsenite Alters Placental Glucose 1, 3, and 4 Transporters in Balb/c Mice.

Inorganic arsenic (iAs) exposure induces a decrease in glucose type 4 transporter (GLUT4) expression on the adipocyte membrane, which may be related to premature births and low birth weight infants in women exposed to iAs at reproductive age. The aim of this study was to analyze the effect of sodium arsenite (NaAsO2) exposure on GLUT1, GLUT3, and GLUT4 protein expression and on placental morphology. Female Balb/c mice (n = 15) were exposed to 0, 12, and 20 ppm of NaAsO2 in drinking water from 8th to 18th day of gestation. Morphological changes and GLUT1, GLUT3, and GLUT4 expression were evaluated in placentas by immunohistochemical and image analysis and correlated with iAs and arsenical species concentration, which were quantified by atomic absorption spectroscopy. NaAsO2 exposure induced a significant decrease in fetal and placental weight (P < 0.01) and increases in infarctions and vascular congestion. Whereas GLUT1 expression was unchanged in placentas from exposed group, GLUT3 expression was found increased. In contrast, GLUT4 expression was significantly lower (P < 0.05) in placentas from females exposed to 12 ppm. The decrease in placental GLUT4 expression might affect the provision of adequate fetal nutrition and explain the low fetal weight observed in the exposed groups.

Fluoride exposure regulates the elongation phase of protein synthesis in cultured Bergmann glia cells.

Fluoride is an environmental pollutant present in dental products, food, pesticides and water. The latter, is the greatest source of exposure to this contaminant. Structural and functional damages to the central nervous system are present in exposed population. An established consequence of the neuronal is the release of a substantial amount of glutamate to the extracellular space, leading to an excitotoxic insult. Glutamate exerts its actions through the activation of specific plasma membrane receptors and transporters present in neurons and in glia cells and it is the over-activation of glutamate receptors and transporters, the biochemical hallmark of neuronal and oligodendrocyte cell death. In this context, taking into consideration that fluoride leads to degeneration of cerebellar cells, we took the advantage of the well-established model of cerebellar Bergmann glia cultures to gain insight into the molecular mechanisms inherent to fluoride neurotoxicity that might be triggered in glia cells. We could establish that fluoride decreases [(35)S]-methionine incorporation into newly synthesized polypeptides, in a time-dependent manner, and that this halt in protein synthesis is the result of a decrease in the elongation phase of translation, mediated by an augmentation of eukaryotic elongation factor 2 phosphorylation. These results favor the notion of glial cells as targets of fluoride toxicity and strengthen the idea of a critical involvement of glia cells in the function and dysfunction of the brain.

Oxidative stress, redox signaling, and autophagy: cell death versus survival.

SIGNIFICANCE: The molecular machinery regulating autophagy has started becoming elucidated, and a number of studies have undertaken the task to determine the role of autophagy in cell fate determination within the context of human disease progression. Oxidative stress and redox signaling are also largely involved in the etiology of human diseases, where both survival and cell death signaling cascades have been reported to be modulated by reactive oxygen species (ROS) and reactive nitrogen species (RNS). RECENT ADVANCES: To date, there is a good understanding of the signaling events regulating autophagy, as well as the signaling processes by which alterations in redox homeostasis are transduced to the activation/regulation of signaling cascades. However, very little is known about the molecular events linking them to the regulation of autophagy. This lack of information has hampered the understanding of the role of oxidative stress and autophagy in human disease progression. CRITICAL ISSUES: In this review, we will focus on (i) the molecular mechanism by which ROS/RNS generation, redox signaling, and/or oxidative stress/damage alter autophagic flux rates; (ii) the role of autophagy as a cell death process or survival mechanism in response to oxidative stress; and (iii) alternative mechanisms by which autophagy-related signaling regulate mitochondrial function and antioxidant response. FUTURE DIRECTIONS: Our research efforts should now focus on understanding the molecular basis of events by which autophagy is fine tuned by oxidation/reduction events. This knowledge will enable us to understand the mechanisms by which oxidative stress and autophagy regulate human diseases such as cancer and neurodegenerative disorders.

Antioxidant gene therapy against neuronal cell death.

Oxidative stress is a common hallmark of neuronal cell death associated with neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, as well as brain stroke/ischemia and traumatic brain injury. Increased accumulation of reactive species of both oxygen (ROS) and nitrogen (RNS) has been implicated in mitochondrial dysfunction, energy impairment, alterations in metal homeostasis and accumulation of aggregated proteins observed in neurodegenerative disorders, which lead to the activation/modulation of cell death mechanisms that include apoptotic, necrotic and autophagic pathways. Thus, the design of novel antioxidant strategies to selectively target oxidative stress and redox imbalance might represent important therapeutic approaches against neurological disorders. This work reviews the evidence demonstrating the ability of genetically encoded antioxidant systems to selectively counteract neuronal cell loss in neurodegenerative diseases and ischemic brain damage. Because gene therapy approaches to treat inherited and acquired disorders offer many unique advantages over conventional therapeutic approaches, we discussed basic research/clinical evidence and the potential of virus-mediated gene delivery techniques for antioxidant gene therapy.

Effect of selenomethionine supplementation in food on the excretion and toxicity of arsenic exposure in female mice.

Selenium (Se) is an essential component of several major metabolic pathways and controls immune function. Arsenic (As) is a human carcinogen with immunotoxic and genotoxic activities, functioning mainly by producing oxidative stress. Due to the ability of Se to interact with As and to possibly block its toxic effects, we investigated the impact of dietary Se-methionine (Se-Met) supplementation on the toxicity of As exposure in vivo in a mouse model. Sufficient and excess levels of Se-Met (0.2 and 2 ppm, respectively) were fed to C57BL/6N female mice exposed to sodium arsenite (3, 6 and 10 mg/kg) in tap water for 9 days. We observed that As exposure increased Se-Met excretion in the urine. Se-Met supplementation increased the relative liver weight and decreased the concentration of total liver proteins in animals exposed to 10 mg/kg of As. Se-Met supplementation maintained a normal pool of glutathione in the liver and increased glutathione peroxidase concentration, although the lipoperoxidation level was increased by Se-Met even without As exposure. Se-Met supplementation helped to maintain the CD4/CD8 ratio of lymphocytes in the spleen, although it increased the proportion of B cells. Se-Met supplementation prior to As exposure increased the secretion of interleukin-4, IL-12 and interferon-γ and the stimulation index of the spleen cells in in vitro assays. Se-Met intake improved the basal immunological parameters but did not reduce the damage caused by oxidative stress after low-dose As exposure.

Arsenite exposure downregulates EAAT1/GLAST transporter expression in glial cells.

Chronic exposure to inorganic arsenic severely damages the central nervous system (CNS). Glutamate (GLU) is the major excitatory amino acid and is highly neurotoxic when levels in the synaptic cleft are not properly regulated by a family of Na⁺-dependent excitatory amino acid transporters. Within the cerebellum, the activity of the Bergmann glia Na⁺-dependent GLU/aspartate transporter (GLAST) excitatory amino acid transporter 1 (EAAT1/GLAST) accounts for more than 90% of GLU uptake. Because exposure to the metalloid arsenite results in CNS toxicity, we examined whether EAAT1/GLAST constitutes a molecular target. To this end, primary cultures of chick cerebellar Bergmann glial cells were exposed to sodium arsenite for 24 h, and EAAT1/GLAST activity was evaluated via ³H-D-aspartate uptake. A sharp decrease in GLU transport was observed, and kinetic studies revealed protein kinase A, protein kinase C, and p38 mitogen-activated protein kinase-dependent decreases in K(M) and V(max) concomitant with diminished chglast transcription. To gain insight into the molecular mechanisms involved in these phenomena, we investigated the generation of reactive oxidative species and the lipid peroxidative damage caused by arsenite exposure. None of these responses were found, although we did observe an increase in nuclear factor (erythroid-derived 2)-like 2 DNA-binding activity correlated with a rise in total glutathione levels. Our results clearly suggest that EAAT1/GLAST is a molecular target of arsenite and support the critical involvement of glial cells in brain function and dysfunction.

Molecular mechanisms of fluoride toxicity.

Halfway through the twentieth century, fluoride piqued the interest of toxicologists due to its deleterious effects at high concentrations in human populations suffering from fluorosis and in in vivo experimental models. Until the 1990s, the toxicity of fluoride was largely ignored due to its "good reputation" for preventing caries via topical application and in dental toothpastes. However, in the last decade, interest in its undesirable effects has resurfaced due to the awareness that this element interacts with cellular systems even at low doses. In recent years, several investigations demonstrated that fluoride can induce oxidative stress and modulate intracellular redox homeostasis, lipid peroxidation and protein carbonyl content, as well as alter gene expression and cause apoptosis. Genes modulated by fluoride include those related to the stress response, metabolic enzymes, the cell cycle, cell-cell communications and signal transduction. The primary purpose of this review is to examine recent findings from our group and others that focus on the molecular mechanisms of the action of inorganic fluoride in several cellular processes with respect to potential physiological and toxicological implications. This review presents an overview of the current research on the molecular aspects of fluoride exposure with emphasis on biological targets and their possible mechanisms of involvement in fluoride cytotoxicity. The goal of this review is to enhance understanding of the mechanisms by which fluoride affects cells, with an emphasis on tissue-specific events in humans.

Arsenic(III) methylation in betaine-nontronite clay-water suspensions under environmental conditions.

This paper reports arsenic methylation in betaine-nontronite clay-water suspensions under environmental conditions. Two nontronites (<0.05 mm), NAu-1 (green color, Al-enriched) and NAu-2 (brown color, Al-poor, contains tetrahedral Fe) from Uley Mine - South Australia were selected for this study. Betaine (pK(a)=1.83) was selected as methyl donor. The reaction between 5 g L(-1) clay, 20 ppm As(III), and 0.4M betaine at 7< or =pH(0)< or =9 under anoxic conditions was studied. The presence of nontronite clays were found to favor As(III) conversion to monomethylarsenic (MMA). Arsenic conversion was found to be as high as 50.2 ng MMA/ng As(III)(0). Conversion of As was found to be more quantitative in the presence of NAu-2 ((Na(0.72)) [Si(7.55) Al(0.16)Fe(0.29)][Al(0.34) Fe(3.54) Mg(0.05)] O(20)(OH)(4)) than NAu-1 ((Na(1.05)) [Si(6.98) Al(0.95)Fe(0.07)][Al(0.36) Fe(3.61) Mg(0.04)] O(20)(OH)(4)). The inherent negative charge at the nontronite tetrahedral layer stabilizes positively charged organic intermediate-reaction species, thereby leading to decreases in the overall methylation activation energy. The outcome of this work shows that nontronite clays catalyze As methylation to MMA via non-enzymatic pathway(s) under environmental conditions.