Polymorphisms in metabolic GSTP1 and DNA-repair XRCC1 genes with an increased risk of DNA damage in pesticide-exposed fruit growers

Abstract

Pesticide exposure is associated with various neoplastic diseases and congenital malformations. Previous studies have indicated that pesticides may be metabolized by cytochrome P450 3A5 or glutathione S-transferases. DNA-repair genes, including X-ray repair cross-complementing group 1 ( XRCC1) and xeroderma pigmentosum group D ( XPD), may also be implicated in the process of pesticide-related carcinogenesis. Thus, we investigated whether various metabolic and DNA-repair genotypes increase the risk of DNA damage in pesticide-exposed fruit growers. Using the comet assay, the extent of DNA damage was evaluated in the peripheral blood of 135 pesticide-exposed fruit growers and 106 unexposed controls. The metabolic genotypes CYP3A5 ( A −44 G) and GSTP1 ( Ile105 Val) and DNA-repair genotypes XRCC1 ( Arg399 Gln, Arg194 Trp, T −77 C) and XPD ( Asp312 Asn, Lys751 Gln) were identified by polymerase chain reaction. Our multiple regression model for DNA tail moment showed that age, high pesticide exposure, low pesticide exposure, GSTP1 Ile-Ile, and XRCC1 399 Arg-Arg genotype were associated with increased DNA tail moment (DNA damage). Further analysis of interaction between GSTP1 and XRCC1 genes that increase susceptibility revealed a significant difference in DNA tail moment for high pesticide-exposed subjects carrying both GSTP1 Ile-Ile with XRCC1 399 Arg-Arg genotypes (2.49 ± 0.09 μm/cell; P = 0.004), compared to those carrying GSTP1 Ile-Val/Val-Val with XRCC1 399 Arg-Gln/Gln-Gln genotypes (1.98 ± 0.15 μm/cell). These results suggest that individuals with susceptible metabolic GSTP1 and DNA-repair XRCC1 genotypes may be at increased risk of DNA damage due to pesticide exposure.