Mechanism underlying the effect of long-term exposure to low dose of pesticides on DNA integrity

Environ Toxicol. 2018 Apr;33(4):476-487. doi: 10.1002/tox.22534. Epub 2018 Jan 23.


Pesticides, including herbicides, insecticides and fungicides, are widely used in intensive agriculture. Recently, the long-term effects of pesticide exposure were found to be associated with many diseases. In this study, we evaluated the long-term effect of low-level exposure to a mixture of pesticides on DNA damage response (DDR) in relation to individual detoxifying variability. A residential population chronically exposed to pesticides was enrolled, biological/environmental pesticide levels; paroxonase 1 (PON-1) activity and 192 Q/R polymorphism and DDR were evaluated at three different periods of pesticide exposure. OGG1-dependent DNA repair activity was decreased in relation to pesticide exposure. The increase of DNA lesions and pesticide levels in the intensive pesticide-spraying period was independent on PON-1 activity. Next, human bronchial epithelial and neuronal cells were used as a model for in vitro evaluation of the mechanistic effect of pesticides. Pesticides induced mitochondrial dysfunction leading to ROS formation. ROS from mitochondria induced DNA damage, which in turn induced OGG1-dependent DNA repair activity through 8-oxoguanine DNA glycosylase 1 (OGG1) expression and activation. Even though OGG1 was overexpressed, an inhibition of its activity, associated with DNA lesion accumulation, was found at prolonged pesticide-exposure. A post-translational regulation of OGG1 by pesticide may be postulated. Taken together, long-term exposure to low-levels of pesticides affects DDR resulting in accumulation of DNA lesions that eventually may lead to cancer or neurological disorders.

Keywords: DNA damage response; OGG1; chronic pesticide exposure; mitochondria destabilization; paraxonase 1 activity.

MeSH terms

  • Adolescent
  • Adult
  • Aryldialkylphosphatase / metabolism
  • Cell Line
  • DNA Damage / drug effects*
  • DNA Glycosylases / genetics*
  • DNA Repair / drug effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mitochondria / metabolism
  • Pesticides / toxicity*
  • Polymorphism, Genetic
  • Reactive Oxygen Species / metabolism
  • Young Adult


  • Pesticides
  • Reactive Oxygen Species
  • Aryldialkylphosphatase
  • DNA Glycosylases
  • oxoguanine glycosylase 1, human