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

Renata Alleva, Nicola Manzella, Simona Gaetani, Tiziana Bacchetti, Massimo Bracci, Veronica Ciarapica, Federica Monaco, Battista Borghi, Monica Amati, Gianna Ferretti, Marco Tomasetti

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)476-487
Number of pages12
JournalEnvironmental Toxicology
Volume33
Issue number4
DOIs
Publication statusPublished - Apr 2018

Keywords

  • 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

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