Sex-dependent changes in activity of detoxification enzymes, insecticide susceptibility, and alterations in protein expression induced by atrazine in Drosophila melanogaster

Atrazine is one of the most widely used agricultural herbicides in the U.S. and the world and is recognized as the most common pesticide contaminant of ground and surface water. The effects of atrazine on the activity of detoxification enzymes and subsequent insecticide susceptibility were elucidated in this study. Drosophila melanogaster was used as the model allowing accurate identification of proteins differentially expressed due to atrazine exposure. Atrazine exposure suppressed cytochrome P450 and general esterase activity in male D. melanogaster, and increased the same activity in females. Both sexes experienced a significant increase in glutathione transferase activity. Drosophila exposed to 1,000 ppm atrazine in a non-nutrient agar for 72 h had body burdens (atrazine + deethylatrazine + deisopropylatrazine) of 11.8 ppm in females and 20.2 ppm in males. Atrazine exposure resulted in significant increases in sensitivity to carbofuran, permethrin, and parathion in both sexes. In DDT exposures, atrazine acted in a sex-dependent manner, as a synergist in females and an antagonist in males.;Proteomic analysis of Drosophila adults exposed to atrazine identified two classes of proteins which were up- or down-regulated in response to atrazine exposure: (1) proteins associated with detoxification and stress responses; and (2) proteins associated with general metabolism. Most of the proteins of interest were differentially expressed in a sex-dependent manner. Changes in expression of these proteins associated with xenobiotic metabolism or stress responses can potentially be used as biomarkers of atrazine exposure. Environmentally relevant exposures to atrazine may not be sufficient to alter the activity of detoxification enzymes or the toxicity of insecticides.