Base excision repair (OGG1 and XRCC1) and metabolism (PON1) gene polymorphisms act on modulation of DNA damage and immune parameters in tobacco farmers

Mutat Res Genet Toxicol Environ Mutagen. 2018 Dec;836(Pt B):9-18. doi: 10.1016/j.mrgentox.2018.04.001. Epub 2018 Apr 4.

Abstract

Pesticides are one of the most frequently investigated chemical, due to their multiple uses in agricultural and public health areas. This study evaluates lymphocytes CBMN (cytokinesis-block micronucleus cytome assay), inflammatory markers, inorganic elements in blood samples, and the relationship of these parameters with XRCC1Arg194Trp, OGG1Ser326Cys and PON1Gln192Arg polymorphisms in a population of tobacco farmers. The study population comprised 129 agricultural workers exposed to pesticides and 91 nonexposed. Farmers had significantly increased NPB (nuclear plasmatic bridge), MN (micronucleus) and NBUD (nuclear bud) frequencies, as well as IL-6 (interleukin 6) and TNF-α (tumor necrosis factor alpha) serum levels, and decreased cytokines CD4+/CD8+ ratio. In the exposed group, XRCC1 Trp/- was correlated with decreased NDI (nuclear division index), and OGG1 Cys/- was associated with higher levels of NPB and decreased levels of IL-6. The combined effects of PON1 Arg/- and XRCC1 Arg/Arg were associated with increased NPB frequencies. In addition, the combination of PON1 Arg/- with XRCC1 Trp/- or OGG1 Cys/- influenced in increased levels of necrosis in farmers. Furthermore, tobacco farmers showed a positive correlation between TNF-α levels and NPB, CD4+/CD8+ ratio and NBUD; and IL-6 levels with both MN and NDI. The duration of years of work at tobacco fields was correlated positively with NBUD frequency. Sulfur, chlorine and potassium were found at increased levels in the exposed group when compared to the nonexposed one. These findings provide evidence that tobacco farmers' exposure have increased DNA damage and alter the immune system's response, and that XRCC1 and OGG1 polymorphisms could influence both biomarkers results.

Keywords: Inflammation; Micronucleus test; OGG1; Occupational exposure; Pesticides; Susceptibility.

MeSH terms

  • Adult
  • Aryldialkylphosphatase / genetics*
  • Case-Control Studies
  • DNA Damage*
  • DNA Glycosylases / genetics*
  • Farmers / statistics & numerical data
  • Female
  • Humans
  • Inflammation Mediators / blood*
  • Interleukin-6 / blood
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Lymphocytes / pathology
  • Male
  • Nicotiana / adverse effects*
  • Occupational Exposure / adverse effects
  • Occupational Exposure / analysis
  • Polymorphism, Genetic*
  • Tumor Necrosis Factor-alpha / blood
  • X-ray Repair Cross Complementing Protein 1 / genetics*

Substances

  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • Aryldialkylphosphatase
  • PON1 protein, human
  • DNA Glycosylases
  • oxoguanine glycosylase 1, human