title: 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.
authors.affiliation: Department of Legal Medicine and Toxicology, University of Granada School of Medicine, Granada, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gómez-Martín
authors.affiliation: Centre for Occupational and Environmental Health (COEH), Centre for Epidemiology, Institute of Population Health, University of Manchester, Manchester, M13 9PL, United Kingdom.
authors.forename: Bashar
authors.initials: B
authors.lastname: Altakroni
authors.affiliation: Department of Legal Medicine and Toxicology, University of Granada School of Medicine, Granada, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Lozano-Paniagua
authors.affiliation: Centre for Occupational and Environmental Health (COEH), Centre for Epidemiology, Institute of Population Health, University of Manchester, Manchester, M13 9PL, United Kingdom.
authors.forename: Geoffrey P
authors.initials: GP
authors.lastname: Margison
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, BS8 2PS, United Kingdom.
authors.forename: Frank
authors.initials: F
authors.lastname: de Vocht
authors.affiliation: Centre for Occupational and Environmental Health (COEH), Centre for Epidemiology, Institute of Population Health, University of Manchester, Manchester, M13 9PL, United Kingdom.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Povey
authors.affiliation: Department of Legal Medicine and Toxicology, University of Granada School of Medicine, Granada, Spain.
authors.forename: Antonio F
authors.initials: AF
authors.lastname: Hernández
mesh_terms: D000328:Adult; D000395:Air Pollutants, Occupational / Q000493:pharmacokinetics / Q000633:toxicity*; D043303:Aryldialkylphosphatase / Q000235:genetics*; D018736:DNA Adducts / Q000235:genetics*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000235:genetics; D000067565:Farmers; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D016273:Occupational Exposure / Q000009:adverse effects* / Q000032:analysis; D010575:Pesticides / Q000493:pharmacokinetics / Q000633:toxicity*; D011110:Polymorphism, Genetic
chemical_list: D000395:Air Pollutants, Occupational; D043303:Aryldialkylphosphatase; D018736:DNA Adducts; D003849:Deoxyguanosine; D005982:Glutathione Transferase; D010575:Pesticides; C048746:7-methyl-2-deoxyguanosine; C413545:glutathione S-transferase T1
keywords: DNA adducts; GST; PON1; biomarkers; genotoxicity; occupational health