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Exposure of tobacco workers handling dried tobacco leaves has been linked to an increased risk of toxicity and respiratory illness due to the presence of nicotine and other chemicals. This study aimed to evaluate the DNA damage caused by the exposure of tobacco growers during the dry leaf classification process and the relation to cellular mechanisms. A total of 86 individuals participated in the study, divided into a group exposed to dry tobacco (n = 44) and a control group (n = 42). Genotoxicity was evaluated using the alkaline comet assay and lymphocyte micronucleus (MN) assay (CBMN-Cyt), and measurement of telomere length. The levels of oxidative and nitrosative stress were evaluated through the formation of thiobarbituric acid reactive species, and nitric oxide levels, respectively. The inorganic elements were measured in the samples using particle-induced X-ray emission method. The combination of variables was demonstrated through principal component analysis and the interactions were expanded through systems biology. Comet assay, MN, death cells, thiobarbituric acid reactive species, and nitrosative stress showed a significant increase for all exposed groups in relation to the control. Telomere length showed a significant decrease for exposed women and total exposed group in relation to men and control groups, respectively. Bromine (Br) and rubidium (Rb) in the exposed group presented higher levels than control groups. Correlations between nitrate and apoptosis; Br and MN and necrosis; and Rb and telomeres; besides age and DNA damage and death cells were observed. The systems biology analysis demonstrated that tobacco elements can increase the nuclear translocation of NFKB dimers inducing HDAC2 expression, which, associated with BRCA1 protein, can potentially repress transcription of genes that promote DNA repair. Dry tobacco workers exposed to dry leaves and their different agents showed DNA damage by different mechanisms, including redox imbalance.

Coal is a mixture of several chemicals, many of which have mutagenic and carcinogenic effects and a key contributor to the global burden of mortality and disease. Previous studies suggest that coal is related to telomeric shortening in individuals occupationally exposed, however little is known about the effects of mining and burning coal on the telomeres of individuals living nearby. Therefore, the aim of this study was to evaluate the influence of this exposure on genomic instability of individuals who live near coal activities, besides correlating results with individual characteristics, inflammatory responses, oxidative stress and inorganic elements. The study involved 80 men participants from three cities around a thermoelectric power plant and one city unexposed to coal and byproducts. DNA was isolated from peripheral blood samples from all individuals and telomeres (TL) were measured by quantitative real time polymerase chain reaction (qPCR). No significant difference was observed between exposed individuals (6.227 ± 2.884 pb) when compared to the unexposed group (5.638 ± 2.452 bp). Nevertheless, TL decrease was associated with age and risk for cardiovascular disease. Higher concentrations of Si and P in blood samples were associated with longer telomeres length. No correlations were observed between TL with comet assay, micronucleus test, oxidative stress, and inflammatory results. Further studies are needed to determine whether these alterations are associated with diseases and premature deaths.

Pollution of aquatic ecosystems is associated with the discharge of mainly industrial and urban effluents, which may cause damage to public health. This study aims to evaluate the cytotoxic, genotoxic, and mutagenic potential of surface water samples under the influence of different anthropogenic effluents in a human-derived liver cell line (HepG2). Samples were collected in Esteio and Sapucaia streams (Rio Grande do Sul; Brazil), which flow into the Sinos River, a source of water supply for more than one million people. Physicochemical and microbiological analyses were performed as well as an analysis of inorganic elements using the PIXE technique (Particle-Induced X-Ray Emission). The presence of pharmaceutical compounds and caffeine was evaluated by gas chromatography coupled to mass spectrometry. The cytotoxicity, genotoxicity, and mutagenicity of the samples were evaluated in HepG2 cells by cell viability assays, alkaline Comet Assay and Cytokinesis-block micronucleus (CBMN) assay. We verified alterations in the physicochemical and microbiological parameters and detected caffeine, diethyltoluamide, and different inorganic elements that corresponded to elements from domestic and industrial effluents and agricultural runoff. Although the samples in the concentration used were not cytotoxic, water samples from all sites induced DNA damage. However, it is difficult to attribute these damages to a specific substance since the factors are a complex mixture of different compounds. Despite this, it is observed that both urban and industrial contributions had a similar effect in the cells evaluated. Such results demonstrate the need to perform biomonitoring of surface waters under anthropogenic influence, especially those that flow into rivers that are a source of public supply water. We also highlight the need for research into emerging pollutants in these aquatic environments.

Tobacco farming has been proving to induce poor health outcomes in agricultural workers, genomic instability being the triggering one. This study evaluated influence of PON1 (paraoxonase 1), SOD2 (superoxide dismutase), OGG1 (8-oxoguanine glycosylase), XRCC1 (X-ray repair cross-complementing protein 1), and XRCC4 (X-ray repair cross-complementing protein 4) genes polymorphisms on DNA damage in 121 subjects occupationally exposed to pesticides mixtures and nicotine at tobacco fields and 121 non-exposed individuals. Inorganic elements (Cl, P, S and Zn) and cotinine levels were found increased in farmers, confirming exposure. Results show higher frequencies of buccal micronucleus (MN), nuclear buds (NBUD), binucleated cells (BN) and damage index (comet assay), reduced telomere length (TL), and increased parameters of oxidative stress in farmers compared to non-exposed individuals. PON1 Gln/Gln genotype was associated with increased MN frequency. SOD2 Val/Val showed association with increased frequency of MN and NBUD and decreased antioxidant activity. The XRCC1 Arg/Arg showed protective effect for MN, BN and TL, which was also positively influenced by OGG1 -/Cys. MN was decreased in XRCC4 -/Ile farmers. These genotypes also showed a risk for antioxidant activity. Our study proposes that PON1 and SOD2 variants play a role in xenobiotic-metabolizing system in farmers, while base excision repair (BER) pathway could be the repair mechanism involved in genomic instability suffered by tobacco farmers.

Environmental exposure to pollution generated by mining and burning coal is inevitable for people living nearby. Therefore, the aim of this study was to evaluate the influence of coal dust on health conditions and genomic instability of individuals who live near coal mines and thermoelectric power plants, and to relate the results to inorganic elements and inflammatory responses. Thus, we evaluated 284 individuals from four cities in the south of Brazil around a region with coal mines and a thermoelectric power plant (one city was considered a negative control). The results of the Comet assay and Micronucleus (MN) test did not show a genotoxic or mutagenic effect related to environmental exposure to coal, but the inflammatory cytokine tumor necrosis factor-α (TNF-α) was increased in all cities around the power plant when compared to the control conditions. Higher levels of MN were associated with body mass index and cardiovascular risk, and higher levels of Damage Index (DI), TNF-α and interleukin1β (IL-1β) with number of cigarettes/day. Principal component analysis (PCA) was used to integrate DNA damage and inflammatory results with inorganic elements. This study also demonstrated the relationship between zinc and MN, copper, and interleukin10 (IL-10), and among silicon and sulfur with DI and nucleoplasmic bridge. A relationship was also observed between the reduction of inorganic elements and both aging and quality of health. The use of different methodologies and the relationship between the results obtained in these studies, including different lifestyles, can increase the understanding of the interaction between this mineral and the health status of residents of regions affected by coal pollution.

Excess fluoride in water can produce changes in tooth enamel mineralization and lead to diseases such as dental or skeletal fluorosis. The present study aimed to assess the genotoxic effects, oxidative stress, and osteoblastic mineralization induced by fluorosilicic acid (FA) in murine bone marrow-derived mesenchymal stem cells (BM-MSCs). BM-MSCs were isolated from the femurs and tibias of rats and cultured under standard conditions. Cells exposure occurred for 3, 7, 14, and 21 days to different concentrations of FA (0.6-9.6 mg/L). Cytotoxicity was observed in 14 and 21 days of exposure for all concentrations of FA (cell proliferation below 60%), and for 3 and 7 days, in which the proliferation was above 80%. Alkaline comet assay results demonstrated significant increased damage at concentrations of 0.3-2.4 mg/L, and the micronucleus test showed increased rates for micronucleus (1.2-2.4 mg/L) and nuclear buds (NBUDs) (0.3-2.4 mg/L) (P < 0.05/Dunnett's test). An alkaline comet assay modified by repair endonuclease (FPG) was used to detect oxidized nucleobases, which occurred at 0.6 mg/L. The oxidative stress was evaluated by lipid peroxidation (TBARS) and antioxidant activity (TAC). Only lipid peroxidation was increased at concentrations of 0.6 mg/L and 1.2 mg/L (P < 0.001/Tukey's test). The osteogenesis process determined the level of extracellular matrix mineralization. The mean concentration of Alizarin red increased significantly in 14 days at the 0.6 mg/L concentration group (P < 0.05/Tukey's test) compared to the control group, and a significant difference between the groups regarding the activity of alkaline phosphatase (ALP) was observed. Unlike other studies, our results indicated that FA in BM-MSCs at concentrations used in drinking water induced genotoxicity, oxidative stress, and acceleration of bone mineralization.