Increased N7‐methyldeoxyguanosine DNA adducts after occupational exposure to pesticides and influence of genetic polymorphisms of paraoxonase‐1 and glutathione S‐transferase M1 and T1

Abstract

There are concerns about genetic risks associated with long-term exposure to pesticides as these compounds may damage DNA, resulting in mutations that eventually lead to cancer, neurological, and reproductive adverse health effects. This study assessed DNA damage in intensive agricultural workers exposed to pesticides by determining the levels of N7-methyldeoxyguanosine (N7-MedG), an adduct known to be a robust biomarker of recent exposure to chemical methylating agents. A cohort of 39 plastic greenhouse workers was assessed for changes in lymphocyte DNA N7-MedG levels between low level and high level exposures during the course of a spraying season. The contributions of genetic polymorphisms of the pesticide-metabolizing enzymes paraoxonase-1 (PON1) and the glutathione S-transferases, GSTM1 and GSTT1, on N7-MedG levels and other potential confounders were also assessed. N7-MedG increased in the period of high pesticide exposure as compared to the low exposure period (0.23 and 0.18 µmol N7-MedG/mol dG for the unadjusted and adjusted linear mixed models, P = 0.02 and 0.08, respectively). Significant decreased levels of erythrocyte acetylcholinesterase and plasma cholinesterase were observed in the high versus low exposure period in both the unadjusted (2.85 U/g hemoglobin and 213.13 U/L, respectively) and adjusted linear mixed models (2.99 U/g hemoglobin and 230.77 U/L, respectively), indicating pesticide intake. In intensive agriculture workers, higher pesticide exposure increased DNA alkylation levels, further demonstrating the genotoxicity of pesticides in man. In addition, pesticide-exposed individuals with inherited susceptible metabolic genotypes (particularly, null genotype for GSTM1 and the PON1 192R allele) appear to have an increased risk of genotoxic DNA damage. Environ. Mol. Mutagen. 56:437-445, 2015. © 2014 Wiley Periodicals, Inc.

Neuropathological Mechanisms Associated with Pesticides in Alzheimer’s Disease

“…Pesticides such as OCs are known to be genotoxic and induce DNA damage [119,120], either via oxidative damage [121] or direct interaction [122] with DNA. Pesticide genotoxicity is usually considered in the context of their oncogenic potential [123,124], particularly during episodes of acute exposure with mutational damage to dividing cells, such as neural stem cells (NSCs) and neural progenitor cells (NPCs).…”

PON1 increases cellular DNA damage by lactone substrates

“…In contrast, the Q allele was associated with higher lymphocyte DNA damage (measured using the alkaline comet assay) in workers employed for spraying OPs but not healthy normal volunteers with no exposure history (Singh et al 2011). Previously, we reported that N7-methyldeoxyguanosine levels in lymphocyte DNA were higher, but not significantly so, in pesticide-exposed individuals with the RR genotype in contrast to those with the QQ genotype (Gómez-Martín et al 2014). In other studies, the PON1 Q192R genotype had no impact on DNA damage, as measured by alkaline comet assay of peripheral blood mononuclear cells (Liu et al 2006) or leucocytes (da Silva et al 2008) of pesticide-exposed workers and controls.…”

Polymorphisms of pesticide-metabolizing genes in children living in intensive farming communities

“…This study provides the first comprehensive data on ten polymorphic variants of genes encoding pesticide-metabolizing enzymes (BCHE, PON1, CYP450, GSTs) in a Spanish population living near an intensive agriculture area where a high use of pesticides is made (Gómez-Martín et al, 2015). Few studies have thoroughly examined the common genetic polymorphisms of phase I and phase II biotransformation enzymes involved in the human metabolism of xenobiotics (Bosch et al, 2006).…”

“…In this study, a healthy Spanish children population living in intensive agriculture areas where pesticides are largely used was screened for genetic polymorphisms in the genes coding for the most important OPs pesticide-metabolizing enzymes (BCHE, PON1, CYP450 and GSTs). In the study area (Southeastern Spain), the amount of insecticides-acaricides-nematocides used accounts for 66.8% of the total pesticide consumption in such area, with OPs representing about 30% of the total amount (tons) of insecticidesacaricides-nematocides sold (Gómez-Martín et al, 2015). The frequencies of SNPs and CNVs as well as the prevalence of haplotypes and combined polymorphisms were explored in order to identify those individuals most at risk for potential adverse health effects from chronic exposure to OPs pesticides.…”