DNA damage in a Chilean population exposed to pesticides and its association with PON1 (Q192R and L55M) susceptibility biomarker

Environ Mol Mutagen. 2022 Apr;63(4):215-226. doi: 10.1002/em.22485. Epub 2022 May 26.

Abstract

The active ingredients in pesticides are known to be genotoxic that can cause mutations, chromosomal aberrations, or other types of DNA damage. Early detection of genotoxicity reduces the risk of developing diseases such as cancer or suffering from reproductive disorders. In turn, the genotoxic risk depends on the intrinsic capability of the individual to metabolize and eliminate the xenobiotic from the organism. This study aimed to determine if two polymorphisms of paraoxonase-1 (PON1), which is involved in the metabolism of several organophosphate (OP) pesticides, are predictors of susceptibility to DNA damage in agricultural workers and inhabitants of rural areas chronically exposed to pesticides. A cross-sectional study was made considering three groups: agricultural workers (occupational exposure, OE, n = 85), rural inhabitants (environmental exposure, EE, n = 60), and an unexposed group conformed by people living far from agricultural areas (U, n = 33). The level of individual DNA damage was measured using the comet assay, and genotyping was done to determine the PON1 Q192R and L55M polymorphisms. Acetylcholinesterase and butyrilcholinesterase activities were also measured to determine exposure to OP. Individuals belonging to EE and OE groups displayed higher levels of DNA damage compared with U group (p < .001). OP exposure was the main predictor of genotoxicity (β = 16.19; 95% CI: 1.85, 30.52), instead of PON1 polymorphisms (β = -12.20; 95% CI: -27.87, 3.48). These results confirm the genotoxic effects of pesticide exposure and suggest that the catalytic efficiency of PON1 to metabolize OP pesticides becomes negligible in individuals with a history of long-term environmental or occupational exposure to these substances.

Keywords: Chilean population; PON1 polymorphisms; cholinesterases; genotoxicity; pesticides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Aryldialkylphosphatase* / genetics
  • Biomarkers
  • Chile
  • Cross-Sectional Studies
  • DNA Damage
  • Humans
  • Organophosphorus Compounds / toxicity
  • Pesticides* / toxicity

Substances

  • Biomarkers
  • Organophosphorus Compounds
  • Pesticides
  • Acetylcholinesterase
  • Aryldialkylphosphatase
  • PON1 protein, human