Date of Graduation

2007

Document Type

Dissertation/Thesis

Abstract

Atrazine is the most heavily used herbicide in the United States by weight and human exposure to the compound is wide spread. This study sought to define the immunotoxic effects of atrazine for two types of atrazine exposure models; maternal exposure to atrazine over a period of weeks and acute exposure of adult immune cells to atrazine. We hypothesized that maternal atrazine exposure from day ten of pregnancy to day ten of lactation would result in significant changes to the adult immune system. At three months of age we observed a gender specific increase in the offsprings’ immune function. Male mice had a significant increase in the response to a heat killed Streptococcus pneumoniae (HKSP) vaccination, and significant increase in the alloreactive T-cell response. At six months of age female mice had a significantly reduced response to HKSP vaccination. This study is the only study of maternal atrazine exposure that directly demonstrates an increase in male immune function, and also demonstrated the effects of maternal exposure can manifest themselves differently in a period of just three months i.e. between three and six months of age. The second type of atrazine exposure we wished to model in these studies was acute adult exposure. Based on the results of Whalen et al. (2003) we hypothesized that atrazine would directly affect the ability of an exposed NK cells to bind to target cells and release their lytic granules. Our results indicate that atrazine treated NK cells can bind to target cells effectively, but are less efficient at releasing the cytolytic granules. Therefore, we concluded that atrazine specifically inhibits lytic granule release without affecting the ability of NK cells to bind their targets. Taken together our findings indicate that atrazine exposure is immunotoxic through multiple routes and durations of exposure. Here we have demonstrated that maternal atrazine is immunotoxic in a gender dependent manner and the nature of the immunotoxcity changes with age. Furthermore, we have partially defined the mechanism by which direct atrazine exposure affects human PBL function as a specific inhibition NK cell granule release.

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