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.

Sperm DNA contains a range of DNA base damage that can arise, in part, from exposure to methylating agents. However, the effects are not fully characterized and so the aim of this study was to investigate associations between semen quality and the levels of N7-methyldeoxyguanosine (N7-MedG), a marker of exposure to methylating agents, and other markers of DNA damage and DNA methylation. Sperm samples were collected from 105 men attending an assisted reproduction clinic as part of a couple undergoing treatment for infertility and semen quality assessed manually according to WHO guidelines. Semen levels of N7-MedG, quantified by immunoslotblot, were significantly higher in men with sperm concentration < 15 × 106/ml (p ≤ 0.01), semen volume < 1.5 ml (p ≤ 0.05) and also in men with any aspect of semen quality below WHO reference levels (p ≤ 0.001). Measures of neutral Comet DNA damage were correlated with semen quality in a univariate analysis but not after adjustment for N7-MedG levels. Sperm concentration was negatively associated with % methylation at the gene for DAZL but no other marker of global or gene-specific DNA methylation. Results support the hypothesis that the known toxic and DNA damaging properties of alkylating agent exposure may have direct deleterious consequences on semen quality.

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