Impact of DNA repair polymorphisms on DNA instability biomarkers induced by lead (Pb) in workers exposed to the metal.

Although the mechanisms of Pb-induced genotoxicity are well established, a wide individual's variation response is seen in biomarkers related to Pb toxicity, despite similar levels of metal exposure. This may be related to intrinsic variations, such as genetic polymorphisms; moreover, very little is known about the impact of genetic variations related to DNA repair system on DNA instability induced by Pb. In this context, the present study aimed to assess the impact of SNPs in enzymes related to DNA repair system on biomarkers related to acute toxicity and DNA damage induced by Pb exposure, in individuals occupationally exposed to the metal. A cross-sectional study was run with 154 adults (males, >18 years) from an automotive batteries' factory, in Brazil. Blood lead levels (BLL) were determined by ICP-MS; biomarkers related to acute toxicity and DNA instability were monitored by the buccal micronucleus cytome (BMNCyt) assay and genotyping of polymorphisms of MLH1 (rs1799977), OGG1 (rs1052133), PARP1 (rs1136410), XPA (rs1800975), XPC (rs2228000) and XRCC1 (rs25487) were performed by TaqMan assays. BLL ranged from 2.0 to 51 µg dL-1 (mean 20 ± 12 µg dL-1) and significant associations between BLL and BMNCyt biomarkers related to cellular proliferation and cytokinetic, cell death and DNA damage were observed. Furthermore, SNPs from the OGG1,XPA and XPC genes were able to modulate interactions in nuclear bud formation (NBUDs) and micronucleus (MNi) events. Taken together, our data provide further evidence that polymorphisms related to DNA repair pathways may modulate Pb-induced DNA damage; studies that investigate the association between injuries to genetic material and susceptibilities in the workplace can provide additional information on the etiology of diseases and the determination of environmentally responsive genes.

Selenium Biofortification Enhanced Grain Yield and Alleviated the Risk of Arsenic and Cadmium Toxicity in Rice for Human Consumption.

Arsenic (As) and Cadmium (Cd) are toxic to rice plants. However, selenium (Se) has the potential to regulate As and Cd toxicity. The present study aimed to evaluate the co-exposure to As5+ and Se6+ species in two rice cultivars, BRS Pampa and EPAGRI 108. The plants were divided into six groups and cultivated until complete maturation of the grains, under greenhouse conditions. Regarding total As and inorganic As (i-As) accumulation in grains, the highest concentrations were found for BRS Pampa. For Se, EPAGRI 108 presented the highest concentration of inorganic and organic Se (i-Se and o-Se). The exposure assessments showed that Se biofortification can mitigate the As accumulation in rice and, consequently, the risk of As and Cd toxicity in grains for human consumption. The combined effect of As and Se in rice plants could represent an alternative to biofortify this food in a safe way and with a higher percentage of bioavailable Se. Although Se is able to mitigate As toxicity in rice plants, in the present study we showed that co-exposure in different cultivars under the same growing conditions may present different responses to As and Se exposure.

Influence of Agaricus bisporus Mushroom on Pb Toxicokinetic in Pregnant Rats.

(Pb) is a toxic metal, responsible for several damages to human health. Agaricus bisporus (Ab) is a mushroom with promising antioxidant properties to be used as an alternative chelator in Pb intoxication. The aim was to understand the Pb toxicokinetic and the potential of Ab as a protective agent. A total of 20 female Wistar rats were distributed into 4 groups (n = 5/group): Control (receiving water); Group Ab 100 mg/kg (gavage); Group Pb 100 mg/L in water; and Group Ab + Pb-100 mg/kg + 100 mg/L (gavage and water). Pb administration occurred daily until the 19th day of pregnancy. On day 19 of gestation, the rats were euthanized, and the blood and tissues were collected for Pb measurement, using an inductively coupled plasma mass spectrometer. The results showed that the levels of Pb in the blood, placenta, and liver of the mothers, and in the brain of the fetuses increased significantly in the Pb group. On the other hand, the combined exposure to Pb + Ab showed a significant decrease in the metal concentration in relation to the Pb group, returning to normal levels. Kidney and bone lead levels also increased significantly in the Pb group. However, in the combined exposure group, levels did not return to the control amounts; there was protection, but the Pb concentration was still significantly higher than in the control. In the brain, no significant differences were observed. In conclusion, we suggest A. bisporus is a natural chelator, because the co-administration of the mushroom was able to interact with Pb ions, minimizing the Pb absorption and distribution. These effects are suggested since A. bisporus have antioxidants and beta glucan that interact with Pb, chelating it and, thus, reducing its toxic effects.

Cellular prion protein offers neuroprotection in astrocytes submitted to amyloid ß oligomer toxicity.

The cellular prion protein (PrPC), in its native conformation, performs numerous cellular and cognitive functions in brain tissue. However, despite the cellular prion research in recent years, there are still questions about its participation in oxidative and neurodegenerative processes. This study aims to elucidate the involvement of PrPC in the neuroprotection cascade in the presence of oxidative stressors. For that, astrocytes from wild-type mice and knockout to PrPC were subjected to the induction of oxidative stress with hydrogen peroxide (H2O2) and with the toxic oligomer of the amyloid ß protein (AßO). We observed that the presence of PrPC showed resistance in the cell viability of astrocytes. It was also possible to monitor changes in basic levels of metals and associate them with an induced damage condition, indicating the precise role of PrPC in metal homeostasis, where the absence of PrPC leads to metallic unbalance, culminating in cellular vulnerability to oxidative stress. Increased caspase 3, p-Tau, p53, and Bcl2 may establish a relationship between a PrPC and an induced damage condition. Complementarily, it has been shown that PrPC prevents the internalization of AßO and promotes its degradation under oxidative stress induction, thus preventing protein aggregation in astrocytes. It was also observed that the presence of PrPC can be related to translocating SOD1 to cell nuclei under oxidative stress, probably controlling DNA damage. The results of this study suggest that PrPC acts against oxidative stress activating the cellular response and defense by displaying neuroprotection to neurons and ensuring the functionality of astrocytes.

Metals in Brazilian family farming grapes and estimated daily intake.

The aim of this study was to determine concentrations of metals in peel, pulp, and seeds of grapes obtained from family farms in Brazil, compare them to the maximum threshold levels and to evaluate the risk by estimating the daily intake (EDI). Grape samples were collected from farms and levels of Cd, Cr, Cu, Mn, Ni, Pb and Zn were assessed via ICP-MS. The highest metal levels were found in grape peels, Cu at the highest concentration (107.6 mg kg-1). Cr, Cu, and Pb were found at concentrations which exceeded maximum threshold levels. The EDI of Cd, Cu and Pb through consumption of grapes for the assessed Brazilian population was 0.29, 1822 and 3.02 µg/kg bw/day, respectively. The EDI of Cu was above the Provisionary Tolerable Daily Intake (PTDI). Thus, there are possible health risks due to the occurrence of Cu in Brazilian grapes.

Elemental plasma content and urinary excretion in vineyard farmers occupationally exposed to pesticides in southern Brazil.

This is a cross-sectional study with data and biological material collection from vineyard farmers in southern Brazil. An interview was carried out through a questionnaire developed according to the reference guide of the state government. Plasma and urine samples were screened for Aluminum, Chromium, Manganese, Copper, Nickel, Cobalt, Zinc, Arsenic, Selenium, Cadmium, Antimony, Barium, Mercury, Lead and Uranium, with a technique for fast determination of these elemental contents in biological material utilizing dynamic reaction cell inductively coupled mass spectrometry. Principal component analysis was used to identify associations between these elemental contents in biological samples and the information obtained from the interviews. The farmers showed some trace elements in plasma and urine at a higher concentration than unexposed populations from other studies. This study highlights recent findings of trace elements in biological material and their association with characteristics of pesticide use. In addition, it also contributes to the gap in the literature regarding trace elements content in plasma and urine of workers exposed to pesticides.

Occupational exposure to potentially toxic elements in the foundry industry: an integrated environmental and biological monitoring.

Industrial foundry processes release metal dust and fumes into the environment. Our study evaluated the exposure to potentially toxic elements in foundry workers. The assessed samples consisted of air particulate matter (n = 42), urine (n = 194), and blood (n = 167). Six workers had high concentrations of arsenic (As) in urine and one of them had a high cadmium (Cd) content in blood, according to Biological Exposure Index from the American Conference of Governmental Industrial Hygienists. The work task significantly influenced the concentrations of cobalt (Co), copper (Cu), iron (Fe), and manganese (Mn) in air, barium (Ba) in urine, and lead (Pb) and cesium (Cs) in blood, while the employment years affected concentrations of Mn, tin (Sn), and uranium (U) in urine and iodine (I) in blood. Arsenic, Pb, Co, and Cd in particulate matter and biological matrices presented significant covariation by working activity, supporting the occupational exposure. In this study, subjects were occupationally exposed to multiple potentially toxic elements. Carcinogenic and noncarcinogenic risks were associated with As, Co, Ni, and Mn exposure.

Cellular prion protein activates Caspase 3 for apoptotic defense mechanism in astrocytes.

The cellular prion protein (PrPC) is anchored in the plasma membrane of cells, and it is highly present in cells of brain tissue, exerting numerous cellular and cognitive functions. The present study proves the importance of PrPC in the cellular defense mechanism and metal homeostasis in astrocytes cells. Through experimental studies using cell lines of immortalized mice astrocytes (wild type and knockout for PrPC), we showed that PrPc is involved in the apoptosis cell death process by the activation of Caspase 3, downregulation of p53, and cell cycle maintenance. Metal homeostasis was determined by inductively coupled plasma mass spectrometry technique, indicating the crucial role of PrPC to lower intracellular calcium. The lowered calcium concentration and the Caspase 3 downregulation in the PrPC-null astrocytes resulted in a faster growth rate in cells, comparing with PrPC wild-type one. The presence of PrPC shows to be essential to cell death and healthy growth. In conclusion, our results show for the first time that astrocyte knockout cells for the cellular prion protein could modulate apoptosis-dependent cell death pathways.

Iron Oxide Nanomaterials for the Removal of Cr(VI) and Pb(II) from Contaminated River After Mariana Mining Disaster.

If not properly treated, water contaminated with chromium (Cr(VI)) and lead (Pb(II)) can cause severe damage to health due to the accumulation of those toxic metals in the human body. Therefore, in this work, three iron oxides, i.e., δ-FeOOH, cystine-functionalized δ-FeOOH (Cys-δ-FeOOH), and Fe3O4, were synthesized and used as adsorbents for Cr(VI) and Pb(II) in water. The results indicated that the Cr(VI) is best adsorbed on cys-δ-FeOOH followed by δ-FeOOH and Fe3O4. It was because of the enhanced interaction between Cr(VI) and the cysteine functional groups on the δ-FeOOH surface. The Cr(VI) adsorption capacity of cys-δ-FeOOH, δ-FeOOH, and Fe3O4 was 217, 14, and 8 mg g-1, respectively. On the other hand, Pb(II) was preferentially adsorbed directly on δ-FeOOH achieving a maximum Pb(II) adsorption capacity of 174 mg g-1. The Pb(II) adsorption capacity of cys-δ-FeOOH and Fe3O4 was 97 and 74 mg g-1, respectively. The Cr(VI) adsorption on cys-δ-FeOOH was best described by the Langmuir-Freundlich model, whereas Pb(II) adsorption on δ-FeOOH followed the Langmuir model. Both Cr(VI) and Pb(II) adsorption on the adsorbents was well-fitted to pseudo-second-order kinetics. The Cr(VI) was more quickly adsorbed by cys-δ-FeOOH (h0 = 0.10 mg g-1 min-1) while the initial adsorption rate of Pb(II) onto δ-FeOOH was significantly faster (h0 = 16.34 mg g-1 min-1). Finally, the synthesized adsorbents were efficient to remove Cr(VI) and Pb(II) from water samples of the Doce river after the environmental disaster of Mariana city, Brazil, thus showing its applicability to remediate real water samples.

Occupational exposure of foundry workers assessed by the urinary concentrations of 18 elements and arsenic species.

BACKGROUND: Some raw materials applied in Fe foundry industries may contain potentially toxic elements. Thus, foundry worker's occupational exposure is a constant health concern. METHOD: In this study, 194 urine samples from foundry workers were analyzed by inductively coupled plasma mass spectrometry for biomonitoring of Al, As, Ba, Cd, Co, Cr, Cs, Cu, Fe, I, Mn, Ni, Pb, Sb, Sn, Se, U and Zn. Moreover, arsenic speciation was performed in representative samples of production sector workers (group A) and administration sector workers (group B). RESULTS: Concentrations of As, Pb, Cd, Cu, Cs, I, Sb in urines from group A were higher than those found for group B. Samples of group A presented Cs, Ni, Mn, Pb, U and Zn concentrations higher than values reported for exposed workers assessed by other studies. Forty-four samples from group A exceed As-reference limits. Group A had approximately seven times more inorganic As (as arsenite) and 14 times more organic As (as dimethyl As) than group B. A statistically significant difference was observed in the elemental concentration in the workers' urine by the time in the function. Moreover, alcohol consumption is probably influencing the urine concentration of As, Ba, Cd, Co, Cu, Fe, I, Se and Zn. CONCLUSION: The monitored foundry workers are exposed to potentially toxic elements and more attention must be given to their health. Therefore, workplace safety conditions must be improved, and constant biomonitoring is necessary to ensure workers' health.

Isolation and characterization of bacteria from a brazilian gold mining area with a capacity of arsenic bioaccumulation.

In Paracatu, a city in Minas Gerais State (Brazil), the gold mineral extraction produces wastes that contribute to environmental contamination by arsenic. This work describes the evaluation of arsenic concentration from soil of a gold mining area in Paracatu and the selection of arsenic resistant bacteria. In the process of culturing enrichment, 38 bacterial strains were isolated and the minimum inhibitory concentration (MIC) was determined in solid medium for each strain. Three bacterial strains named P1C1Ib, P2Ic and P2IIB were resistant to 3000 mg L-1 of arsenite. Analysis of 16S rDNA gene sequences revealed that these bacteria belong to Bacillus cereus and Lysinibacillus boronitolerans species. After cultivation of the strains P1C1Ib, P2Ic and P2IIIb, 69.38%-71.88% of arsenite and 82.39%-85.72% of arsenate concentrations were reduced from the culture medium, suggesting the potential application of theses strains in bioremediation processes.

Determination of 17α-ethinylestradiol and toxic metals in surface waters, and estimation of daily intake.

The presence of substances such as hormones and toxic metal in aquatic ecosystem is interesting to the scientific community due to their adverse effects. We quantified 17α-ethynylestradiol (EE2) and toxic metals in the surface waters from Sorocaba and Pirajibu Rivers, in São Paulo State, and we estimated the daily intake for hormone, based on the amount of water consumed. EE2, Cd, Hg, As, Pb, and Mn were seasonally quantified in six different locations along the rivers. EE2 was evaluated by high-performance liquid chromatography. Toxic metals were determined by inductively coupled plasma mass spectrometer. Considering the entire sample year, EE2 concentrations ranged from 4.5 to 48.2 µg L-1. Comparing Sorocaba and Pirajibu rivers, the sample point in the entrance of the Pirajibu River through the city of Itu, São Paulo State, had higher amounts of EE2. Regarding metals, all results are according to the Brazilian and World Health Organization guidelines for drinking-water quality, except for Mn levels, which were higher than the limits in Autumn season in two locations. The estimated daily intake ranged from 13.45 to 40.9 µg/day/person. In conclusion, concentrations of EE2 in the Sorocaba and Pirajibu Rivers were higher than in other countries. The levels were as high as an intake of one pill for each person every day (considering an oral contraceptive has 0.03 mg of ethinylestradiol). Even though concentrations of toxic elements are in accordance with the Brazilian Regulation and World Health Organization, legislation for hormones and drugs needs to advance.

Availability of arsenic in rice grains by in vitro and in vivo (humans) assays.

BACKGROUND: Rice grains are consumed by approximately half of the world's population. This cereal has higher arsenic (As) concentrations in grains than wheat or barley. Arsenic determination in food and/or in vitro studies are important for risk assessment; however, it is not enough to assess the real human exposure. METHOD: In vitro bioaccessibility was carried out in husked-rice using gastric and intestinal solutions similar to humans. Also, As naturally found in husked-rice was evaluated by in vivo bioavailability in humans. For this purpose, diets from the 1st and 2nd days were free of foods known to be high in As; 3rd and 4th days the diets were composed by rice and water and; 5th and 6th the diet was similar the 1st and 2nd days. During all experimentation, a representative aliquot of each meal, blood and urine were collected for total As (t-As) determination. Arsenic species were determined in the urine. RESULTS: t-As in husked rice varied from 157.3 ±â€¯30.6 to 240.2 ±â€¯85.2 µg kg-1. The in vitrobioaccessible fractions ranged from 91 to 94%. Inorganic As (i-As) ranged from 99.7 ±â€¯11.2 to 159.5 ±â€¯29.4 µg kg-1. For the in vivo assay, t-As concentrations in the woman and man blood were about 3 µg mL-1 from the 1st to 6th day. Arsenic from the rice ingested was excreted by urine about 72 h after ingestion. The t-As and dimethyl As (DMA) in urine ranged from 3.59 to 47.17 and 1.02 to 2.55 µg g-1 creatinine for the volunteers, indicating a two-fold DMA-increase in urine after ingestion of husked-rice. CONCLUSION: After rice ingestion, As was quickly metabolized. The higher As concentrations were found in urine 72 h after rice ingestion. The main As-specie found in urine was DMA, indicating that methylation of As from rice followed by urine excretion is the main biological pathway for As excretion.

A high-throughput analytical tool for quantification of 15 metallic nanoparticles supported on carbon black.

Metallic nanoparticles (NPs) have been widely used in different areas of science. Usually, they are immobilized on a low-cost support for catalysis purposes. However, there is a lack of studies for specific methods for analytical quantification since the extraction of these metallic NPs from the matrix is still a challenge. In this work, 15 metallic NPs were synthesized (Pt, Pd, Au, Ag, Rh, Ru, Nb, Mn, Co, Cu, Zr, Sn, Ce, Ni and W) supported on a commercial carbon black (Vulcan XC72). Then, six different methods were employed for sample preparation and further determination by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The results can be divided in three groups concerning the extraction of metallic NPs: the first group could be extracted from the matrix with nitric acid, for the second one it was necessary to employ a digestion at 25 °C (room temperature), and finally a third group which was found to be independent of acid and temperature. These findings can contribute to future research in the field of catalysis to improve their characterization regarding the metallic NPs.

Lead, Cadmium, and Arsenic Bioaccessibility of 24 h Duplicate Diet Ingested by Preschool Children Attending Day Care Centers in Brazil.

Lead, known as a metal with high neurotoxicity to children, cadmium, which is a carcinogenic and bioaccumulative contaminant, and arsenic, a class 1 carcinogenic according to the International Agency for Research on Cancer, are toxic elements (TEs) whose relevant route of exposure may be diet. We determined the bio-accessible fraction of lead, cadmium, and arsenic from the diet of preschool children from two day care centers (DCC). A cross-sectional study was conducted with 64 one⁻four-year-old children from two DCCs where the 24-h duplicate diet samples were collected. The diet samples were analyzed by ICP-MS for lead, cadmium, and arsenic total concentrations (n = 64) and their bio-accessibility were analyzed for a subsample (n = 10). The dietary intake (DI) mean for lead, cadmium, and arsenic were 0.18 ± 0.11 µg kg-1 bw, 0.08 ± 0.04 µg kg-1 bw, and 0.61 ± 0.41 µg kg-1 bw, respectively. All DI calculated for TEs, considering total intake, were found lower than the tolerable limits (TL) (European Union, or World Health Organization, WHO, when applicable) except for one child's Pb intake. Bio-accessibilities ranged between 0% to 93%, 0% to 103%, and 0% to 69%, for lead, cadmium, and arsenic, respectively. Although DI for TEs has been found lower than TL, these reference values have been recently decreased or withdrawn since it was for lead and arsenic whose TL were withdrawn by WHO.

Occupational Exposure to Pesticides in Tobacco Fields: The Integrated Evaluation of Nutritional Intake and Susceptibility on Genomic and Epigenetic Instability.

Pesticides used at tobacco fields are associated with genomic instability, which is proposed to be sensitive to nutritional intake and may also induce epigenetic changes. We evaluated the effect of dietary intake and genetic susceptibility polymorphisms in MTHFR (rs1801133) and TERT (rs2736100) genes on genomic and epigenetic instability in tobacco farmers. Farmers, when compared to a nonexposed group, showed increased levels of different parameters of DNA damage (micronuclei, nucleoplasmic bridges, and nuclear buds), evaluated by cytokinesis-block micronucleus cytome assay. Telomere length (TL) measured by quantitative PCR was shorter in exposed individuals. Global DNA methylation was significantly decreased in tobacco farmers. The exposed group had lower dietary intake of fiber, but an increase in cholesterol; vitamins such as B6, B12, and C; ß-carotene; and α-retinol. Several trace and ultratrace elements were found higher in farmers than in nonfarmers. The MTHFR CT/TT genotype influenced nucleoplasmic bridges, nuclear buds, and TL in the exposed group, whereas TERT GT/TT only affected micronucleus frequency. We observed a positive correlation of TL and lipids and an inverse correlation of TL and fibers. The present data suggest an important role of dietary intake and subjects' genetic susceptibility to xenobiotics-induced damages and epigenetic alterations in tobacco farmers occupationally exposed to mixtures of pesticides.

Lead (Pb) exposure induces disturbances in epigenetic status in workers exposed to this metal.

Previous studies showed that lead (Pb) exposure may modulate gene expression by changes in the epigenetic status. However, little is known about the impact of Pb exposure and alterations on DNA methylation patterns in humans exposed to this metal. The aim of this study was to assess the consequences of exposure to Pb on DNA global methylation, in order to gain a better understanding of the interactions between Pb exposure and epigenetic effects. The study included 100 male workers employed in automotive battery factories from Paraná State, Brazil. Concentrations of Pb in blood (B-Pb) and plasma (P-Pb) were determined by ICP-MS, the percentage (%) of global DNA methylation was determined by quantification of 5-methylcytosine using indirect ELISA, and sociodemographic data collected by questionnaire by trained interviewers. The mean age was 37 ± 10 (18-67 years); 18% of participants were smokers, while 32% reported consumption of alcoholic beverages. The B-Pb and P-Pb levels were 20 ± 11 and 0.56 ± 0.64 µg/dl, respectively; % global DNA methylation was 2.8 ± 1.1% (ranging from 1.1 to 6.5%). B-Pb and P-Pb concentrations were significantly correlated. Furthermore, a marked association was noted between Pb biomarkers and DNA global methylation. Taken together, our data demonstrated that Pb exposure induced alterations on DNA global methylation in workers who were exposed to the metal and consequently may result in disturbances in the regulation of gene expression, leading to potentially several health adverse effect outcomes.