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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.

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.