Chronic occupational exposure endured by tobacco farmers from Brazil and association with DNA damage

Abstract

Tobacco farming is an important economic income in Brazil, although it has been challenged as regard the occupational exposure to both pesticides and nicotine endured by farmers. Chronic occupational exposure to complex mixtures can lead to health hazardous. We examined genomic instability and epigenetic changes in tobacco farmers occupationally exposed to pesticide mixtures and nicotine at tobacco fields. DNA damage was assessed by alkaline comet assay in blood cells. Genomic DNA was isolated, and telomere length was measured using quantitative polymerase chain reaction assay. We measured 5-methyl-2'-deoxycytidine, a marker of global DNA methylation, and p16 promoter methylation. The oxidative profile was evaluated by trolox equivalent antioxidant capacity and lipid peroxidation (thiobarbituric acid reactive substances) in serum. Exposure parameters, plasma cotinine and inorganic element levels, were also measured. DNA damage was significantly elevated for farmers in relation to unexposed group (P < 0.001; Mann-Whitney test) and positively associated with years of exposure. Inverse relationship between DNA damage and total equivalent antioxidant activity was demonstrated for exposed and unexposed groups. Exposed group showed significantly shorter telomeres (P < 0.001; unpaired t-test) and DNA hypomethylation (P < 0.001; unpaired t-test), as well as p16 hypermethylation (P = 0.003; Mann-Whitney test). Lipid peroxidation was increased for exposed group in relation to unexposed one (P = 0.02; Mann-Whitney test) and presented a positive correlation with global DNA methylation (P = 0.0264). Farmers have increased plasma cotinine levels (P < 0.001) and inorganic elements (phosphorus, sulphur and chlorine) in relation to unexposed group. Elevated oxidative stress levels due to chronic occupational pesticide mixtures and nicotine exposure in tobacco farmers were associated with higher DNA damage, shorter telomeres and altered DNA methylation. Telomere-accelerated attrition due to exposure may be potential intermediate step before a disease state.

Associação de dados clínicos e laboratoriais de residentes da área rural com exposição crônica ao glifosato

“…The main form of pesticide application reported by the study volunteers was the costal pump, which is cited by several authors as an additional factor of exposure, followed by application using tractors without a booth, which is mistakenly treated as safe by volunteers using majority, only ear protectors during application using this vehicle. These results are consistent with other studies carried out in other regions of Brazil, showing a great use of this pesticide and the absence of care at the time of use (Cattelan et al, 2018;Kahl et al, 2018;Santos et al, 2019).…”

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

“…Recently, a consortium called Agricultural Health Study (AHS) has approached the influence of exposure to pesticides in crop farms to telomere length, although those studies are not clear which pesticides, whether as pure or mixture use, and which crop are being investigated [ 44 , 45 ]. Our group demonstrated shorter telomere length in tobacco farmers, exposed to both pesticides and nicotine from tobacco leaves, is associated with increased oxidative stress levels and trace and ultratrace element status [ 17 , 46 ]. Along with the available data in literature, the influence of pesticides on telomere length demonstrates that occupational exposure to pesticides presents a long-term effect on farmers [ 7 , 11 , 13 , 21 , 30 , 31 , 42 , 44 , 47 ].…”

“…It has been suggested that Ni carcinogenic potential relates to its ability to accelerate epigenetic changes including DNA methylation. On a former study from our group, the shorter TL in tobacco farmers was related to hypermethylation of the p16 gene [ 46 ]. Nickel was found to promote gene-specific hypermethylation of the tumor suppressor p16 in several studies (reviewed by [ 70 ]).…”

Detection and Comparative Analysis of Methylomic Biomarkers of Rheumatoid Arthritis

“…Ttest evaluated the statistical significance of a feature's differential values between two groups of samples (Kim, 2015;Gharbali et al, 2018;Jankowski et al, 2018). This study focused on the differential methylated residues between the RA patients and the siblings and assumed the independences between the two groups of samples (Lotsch et al, 2013;Kahl et al, 2018).…”