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In this study, we evaluated the long\u2010term effect of low\u2010level 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\u20101) activity and 192 Q\/R polymorphism and DDR were evaluated at three different periods of pesticide exposure. OGG1\u2010dependent DNA repair activity was decreased in relation to pesticide exposure. The increase of DNA lesions and pesticide levels in the intensive pesticide\u2010spraying period was independent on PON\u20101 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\u2010dependent DNA repair activity through 8\u2010oxoguanine 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\u2010exposure. A post\u2010translational regulation of OGG1 by pesticide may be postulated. Taken together, long\u2010term exposure to low\u2010levels of pesticides affects DDR resulting in accumulation of DNA lesions that eventually may lead to cancer or neurological disorders.<\/jats:p>","DOI":"10.1002\/tox.22534","type":"journal-article","created":{"date-parts":[[2018,1,23]],"date-time":"2018-01-23T08:32:39Z","timestamp":1516696359000},"page":"476-487","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Mechanism underlying the effect of long\u2010term exposure to low dose of pesticides on <scp>DNA<\/scp> integrity"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7327-3833","authenticated-orcid":false,"given":"Renata","family":"Alleva","sequence":"first","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy"},{"name":"International Society of Doctors for the Environment (ISDE) Arezzo 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