Atrazine & its metabolites are present at high levels in a high percentage of water supplies in agro-intensive areas. Given that humans in these areas use water from these contaminated sources, we investigated the long-term effects of prenatal & neonatal exposure to atrazine on the immune system. To determine these effects, pregnant Balb/C dams were exposed to 700 g atrazine per day from day 10 postcoitus to day 10 postpartum. All offspring were allowed to nurse their natural mother & were weaned at 25 days of age. Offspring were randomly segregated by sex & exposure & aged to approximately 1 year of age at which time their spleens were removed for analysis. Phenotypic analysis was performed using flow cytometry & cytokine production was measured by cytometric bead array after anti- CD3/anti-CD28 stimulation of the spleen cells. The spleen cells were stained to determine total T cells, CD8+ T cells, CD4+ T cells, B cells, granulocytes, macrophages, NK cells, nTreg & LAG-3+-Treg cells. Cytokines measured include interleukin (IL)-2, IL-4, IL-6, interferon- , tumor necrosis factor- , IL-17A, IL-10 & TGF- 1 which measures the functional ability of the cells to respond to stimulation as well as allows for further classification of the T cells into TH1, TH2, TH17 cells. One year old female offspring had significant decreases in the percentage of CD8+ T cells & significant increases in granulocytes & NK cells. There was a trend (same type of change; 1 of 2 runs significant) towards an increase in LAG-3+ Treg cells. Male offspring showed significant decreases in the percentage of CD8+ T cells & significant increases in CD4+ as well as a trend towards a significant increase in NK cells. This is the first time the long term changes in immune cell phenotype have been documented after a prenatal & neonatal exposure to atrazine & it demonstrates that these early life exposures can result in permanent changes to the immune system.
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC