Abstract

Introduction Reactive oxygen species, potentially formed through environmental or lifestyle exposures, can overwhelm an organism’s antioxidant capabilities resulting in oxidative stress. Long-term oxidative stress is linked with chronic diseases including breast, prostate, and lung cancers. We utilised a longitudinal study of corn farmers and non-farming controls in Iowa to examine the impact of exposure to atrazine and 2,4-dichlorophenoxyacetic acid (2,4-D) on markers of oxidative stress. These pesticides are associated with oxidative stress in vivo, as well as cancer, and are among the most widely used herbicides in the United States. Methods The study included 225 urine samples collected through the growing season (pre-planting, planting, growing season, harvest, and off-season) of 10 controls who did not apply pesticides occupationally and 30 farmers who did; all were non-smoking men ages 40 to 60 years. Atrazine mercapturate (an atrazine metabolite), 2,4-D, and oxidative stress markers (malondialdehyde [MDA], 8-hydroxy-2′-deoxyguanosine [8-OHdG], and 8-„isoprostaglandin-F2α [8-isoPGF]) were measured in urine samples. We calculated β estimates and p-values for each pesticide-oxidative stress marker combination using linear mixed-effect models adjusted for creatinine, time, and other covariates in order understand the impact of exposure to these herbicides on oxidative stress. Results Overall, farmers had higher urinary atrazine mercapturate and 2,4-D levels compared to controls. In multivariate linear mixed-effect regression models, after natural log transformation, 2,4-D was associated with elevated levels of 8-OHdG (β = 0.047, p = 0.048) and 8-isoPGF (β = 0.076, p = 0.075). We saw no associations with 2,4-D and MDA. Atrazine mercapturate was not associated with any of the oxidative stress markers. Discussion Our data suggest 2,4-D exposure may be associated with oxidative stress because of increases of 8-OHdG, a marker of oxidative DNA damage, and 8-isoPGF, a product of lipoprotein peroxidation with exposure. Future studies should attempt to understand the role of 2,4-D-induced oxidative stress in the pathogenesis of human disease, particularly cancer.

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