Blood levels of 21 metals and metalloids in riverside villagers of the Brazilian Amazon: A human biomonitoring study with associations with sociodemographic, dietary, and lifestyle factors.

Human biomonitoring of toxic and essential trace elements is critically important for public health protection. Amazonian riverine communities exhibit distinctive dietary patterns, heavily reliant on locally sourced fish, fruits, and vegetables. These habits may result in unique exposure profiles compared to urban populations. However, comprehensive assessments of their exposure to toxic and essential metals are lacking, representing a critical gap in understanding the health risks faced by these communities. This study aimed to establish baseline levels of 21 metals and metalloids in human blood and explore the influence of sociodemographic factors, dietary habits, and lifestyle choices as potential sources of exposure to these elements. A cross-sectional biomonitoring investigation was conducted with 1,024 individuals from 13 communities in the Tapajós and Amazon Basins (Pará, Brazil). Most of the elements in study was determined for the first time in the region. Blood samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). The levels of all elements were summarized by quantiles and compared with cutoff values from other Brazilian populations. Multiple linear regression was used to assess possible associations between element concentrations and sociodemographic characteristics, dietary habits, and lifestyle choices. High detection rates (64%-100%) were observed, indicating the widespread presence of these elements. Elevated blood concentrations were found for mercury (median 21.1 µg.L-1, interquartile range: 12-34 µg.L-1), selenium (median 166 µg.L-1, interquartile range: 137-208 µg.L-1), and lead (median 34 µg.L-1, interquartile range: 20.8-64 µg.L-1). Regression analysis revealed a positive association between mercury levels and fish consumption, while manioc flour intake showed no relationship to lead levels. In conclusion, our findings emphasize the need for continued monitoring and public policy development for these vulnerable populations. Further studies should assess long-term trends and investigate the health implications of prolonged exposure to diverse chemicals in Amazonian riverside communities.

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.

Acute Toxicity and DNA Instability Induced by Exposure to Low Doses of Triclosan and Phthalate DEHP, and Their Combinations, in vitro.

Triclosan (TCS) is an antimicrobial agent widely used in personal care products (PCP) and the di-(2-ethyl hydroxy-phthalate) (DEHP) is a chemical compound derived from phthalic acid, used in medical devices and plastic products with polyvinyl chloride (PVCs). As result of their extensive use, TCS and DEHP have been found in the environment and previous studies demonstrated the association between their exposure and toxic effects, mostly in aquatic organisms, but there is a shortage in the literature concerning the exposure of TCS and DEHP in human cells. The aim of the present study was to assess the impact of exposure to TCS and DEHP, as well as their combinations, on biomarkers related to acute toxicity and DNA instability, in HepG2 cells, by use of cytokinesis-block micronucleus cytome (CBMNCyt) assay. For that, the cultures were exposed to TCS, DEHP and combinations at doses of 0.10, 1.0, and 10 µM for the period of 4 h and the parameters related to DNA damage (i.e., frequencies of micronuclei (MN) and nuclear buds (NBUDs), to cell division (i.e., nuclear division index (NDI) and nuclear division cytotoxic index (NDCI) and to cell death (apoptotic and necrotic cells) were scored. Clear mutagenic effects were seen in cells treated with TCS, DEHP at doses of 1.0 and 10 µM, but no combined effects were observed when the cells were exposed to the combinations of TCS + DEHP. On the other hand, the combination of the toxicants significantly increased the frequencies of apoptotic and necrotic cells, as well as induced alterations of biomarkers related to cell viability (NDI and NDCI), when compared to the groups treated only with TCS or DEHP. Taken together, the results showed that TCS and DEHP are also able to induce acute toxicity and DNA damage in human cells.

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.

Comparative in vitro study of photodynamic activity of hypericin and hypericinates in MCF-7 cells.

In this work we present a comparative in vitro study of photodynamic activity between hypericin (HYP) and some hypericinates (hypericin ionic pair with lysine or N-methylglucamine) in human mammary adenocarcinoma cells (MCF-7). The toxicity and phototoxicity of hypericin and hypericinates were compared, as well as their cellular uptake and localization and mutagenic, genotoxic and clonogenic capacity. Our results demonstrate that different cationic moieties promote differences in the hypericinate solubility in a biological environment, and can influence the cellular localization and the phototoxicity of the photosensitizer. It was verified that hypericinates have better efficiency to generate singlet oxygen than HYP, and a lower aggregation in biological medium. In vitro assays have shown that HYP and the hypericinates are able to permeate the MCF-7 cell membrane and accumulated in organelles near the nucleus. The difference in location, however, was not determinant to the cell death mechanism, and a higher prevalence of apoptosis for all studied compounds occurred. The photodynamic studies indicated that hypericinates were more effective than HYP and were able to inhibit the formation of cellular colonies, suggesting a possible ability to prevent the recurrence of tumors. It also appears that all compounds have relative safety for mutagenicity and genotoxicity, which opens up a further safe route for application in in vivo studies.

Generation of Advanced Glycation End-Products (AGEs) by glycoxidation mediated by copper and ROS in a human serum albumin (HSA) model peptide: reaction mechanism and damage in motor neuron cells.

Glucose, in the presence of reactive oxygen species (ROS), acts as an as an oxidative agent and drives deleterious processes in Diabetes Mellitus. We have studied the mechanism and the toxicological effects of glucose-dependent glycoxidation reactions driven by copper and ROS, using a model peptide based on the exposed sequence of Human Serum Albumin (HSA) and containing a lysine residue susceptible to copper complexation. The main products of these reactions are Advanced Glycation End-products (AGEs). Carboxymethyl lysine and pyrraline condensed on the model peptide, generating a Modified Peptide (MP). These products were isolated, purified, and tested on cultured motor neuron cells. We observed DNA damage, enhancement of membrane roughness, and formation of domes. We evaluated nuclear abnormalities by the cytokinesis-blocked micronucleus assay and we measured cytostatic and cytotoxic effects, chromosomal breakage, nuclear abnormalities, and cell death. AGEs formed by glycoxidation caused large micronucleus aberrations, apoptosis, and large-scale nuclear abnormalities, even at low concentrations.

Potential risks of the residue from Samarco's mine dam burst (Bento Rodrigues, Brazil).

On November 5th, 2015, Samarco's iron mine dam - called Fundão - spilled 50-60 million m3 of mud into Gualaxo do Norte, a river that belongs to Rio Doce Basin. Approximately 15 km2 were flooded along the rivers Gualaxo do Norte, Carmo and Doce, reaching the Atlantic Ocean on November 22nd, 2015. Six days after, our group collected mud, soil and water samples in Bento Rodrigues (Minas Gerais, Brazil), which was the first impacted area. Overall, the results, water samples - potable and surface water from river - presented chemical elements concentration according to Brazilian environmental legislations, except silver concentration in surface water that ranged from 1.5 to 1087 µg L-1. In addition, water mud-containing presented Fe and Mn concentrations approximately 4-fold higher than the maximum limit for water bodies quality assessment, according to Brazilian laws. Mud particle size ranged from 1 to 200 µm. SEM-EDS spot provided us some semi quantitative data. Leaching/extraction tests suggested that Ba, Pb, As, Sr, Fe, Mn and Al have high potential mobilization from mud to water. Low microbial diversity in mud samples compared to background soil samples. Toxicological bioassays (HepG2 and Allium cepa) indicated potential risks of cytotoxicity and DNA damage in mud and soil samples used in both assays. The present study provides preliminary information aiming to collaborate to the development of future works for monitoring and risk assessment.

Genotoxic assessment on river water using different biological systems.

This paper reports genotoxicity and toxicity data in water samples collected in Sinos River, an important water course in the hydrographic region of Guaíba Lake, Rio Grande do Sul State, south of Brazil. This river is exposed to intense anthropic influence by numerous shoes, leather, petrochemical, and metallurgy industries. Water samples were collected at two moments (winter 2006 and spring 2006) at five sites of Sinos River and evaluated using in vitro V79 Chinese hamster lung fibroblasts (cytotoxicity, comet assay and micronucleus test) and Allium cepa test (toxicity and micronucleus test). Comet and micronucleus tests revealed that water samples collected exerted cytotoxic, toxic, genotoxic and mutagenic effects. The results showed the toxic action of organic and inorganic agents found in the water samples in all sites of Sinos River, for both data collections. The main causes behind pollution were the domestic and industrial toxic discharges. The V79 and A. cepa tests were proved efficient to detect toxicity and genotoxicity caused by complex mixtures. This study also showed the need for constant monitoring in sites with strong environmental degradation caused by industrial discharges and urban sewages.