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

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.

Awareness of Cancer Risk Factors and Its Signs and Symptoms in Northern Tanzania: a Cross-Sectional Survey in the General Population and in People Living with HIV

“…With the majority of the population as small-scale farmers with substantial fertilizer use, the question of pesticide use is important for these residents. Use of certain pesticides, DDT (dichlorodiphenyltrichloroethane) in particular, has been investigated in relation to cancer, but is a probable and not a confirmed carcinogen (group 2A (updated in 2017 [33,44,45]. In Kilimanjaro, pesticides have been used for more than six decades on coffee plantations and recently opened horticulture farms.…”

Oxidative stress and DNA damage in agricultural workers after exposure to pesticides

“…Some investigations report that oxidative stress and DNA damage caused by pesticide exposure are involved in mechanisms linking pesticide exposure with adverse health effects [19][20][21].…”

Genetic profile for the detection of susceptibility to poisoning by exposure to pesticides

“…Pesticides or some of their metabolites are xenobiotics that are toxic to humans; thus, some genes express enzymes which metabolize pesticides and their metabolites. The complex CYP450 plays an important role in phase 1 xenobiotic metabolism and consist of a broad family of monooxygenases, where each enzyme is highly polymorphic [9,31]. Glutathione transferases (GST) are a family of phase 2 metabolizing enzymes which catalyze the catabolism of electrophilic xenobiotics that produce free radical-induced oxidative stress, where the isoform π (GSTP1) is the variant that metabolizes pesticides [13,32,33].…”

“…Glutathione transferases (GST) are a family of phase 2 metabolizing enzymes which catalyze the catabolism of electrophilic xenobiotics that produce free radical-induced oxidative stress, where the isoform π (GSTP1) is the variant that metabolizes pesticides [13,32,33]. PON1 is a phase 2 xenobiotic metabolizing enzyme that metabolizes organophosphate-type pesticides, thus avoiding cholinergic poisoning of farmers exposed to this type of pesticide [31,[34][35].…”