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

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

Author information

1
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
2
International Society of Doctors for the Environment (ISDE), Arezzo, Italy.
3
Department of Molecular and Clinical Sciences, Polytechnic University of Marche, Ancona, Italy.
4
Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona, Italy.
5
Department of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy.

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.

KEYWORDS:

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

PMID:
29359425
DOI:
10.1002/tox.22534
[Indexed for MEDLINE]

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