GSTP1 Genetic Polymorphism Is Associated with a Higher Risk of DNA Damage in Pesticide-Exposed Fruit Growers

Abstract

Pesticide exposure is associated with various neoplastic diseases and congenital malformations. Animal studies also indicated that pesticides may be metabolized by cytochrome P450 3A5 (CYP3A5) enzymes, paraoxonases (PON1 and PON2), or glutathione S-transferases (GSTM1, GSTT1, and GSTP1). However, little is known about the genotoxicity of pesticides in people with various genetic polymorphisms of human CYP3A5, PON1, PON2, GSTM1, GSTT1, and GSTP1. Thus, this study was designed to investigate whether various metabolic genotypes are more susceptible to DNA damage in pesticide-exposed fruit growers. Using the Comet assay, the extent of DNA damage was evaluated in the peripheral blood of 91 fruit growers who experienced pesticide exposure and 106 unexposed controls. Questionnaires were administered to obtain demographic data, cigarette smoking habits, medical, and occupational histories. The genotypes for CYP3A5, PON1, PON2, GSTM1, GSTT1, and GSTP1 genes were identified by PCR. The results showed that subjects experiencing high or low pesticide exposure had a significantly greater DNA tail moment (DAN damage) than did controls. The multiple regression model also revealed that age (P < 0.01), high pesticide exposure (P < 0.01), low pesticide-exposure (P < 0.01), and CYP3A5 (P = 0.04) and GSTP1 (P = 0.02) genotypes were significantly associated with an increased DNA tail moment. Further analysis of environmental and genetic interactions revealed a significant interaction for GSTP1 genotypes to influence DNA tail moment for the high pesticide exposure group. These results suggest that individuals with susceptible metabolic GSTP1 genotypes may experience an increased risk of DNA damage elicited by pesticide exposure.