Developmental Effects of Ethanol Exposure: Role of Oxidative Stress Pathways

Signal transduction pathways are sensitive to environmental stresses, and oxidative stress is a fundamental process nearly all organisms experience. Drosophila melanogaster reared in ethanol-treated food have reduced viability and developmental delays, among other phenotypes. Previous work has shown that upregulation of insulin production can rescue these phenotypes, and unpublished data from the French lab implicates the PI3K pathway in mediating ethanol-induced lethality. Given that ethanol is known to induce oxidative stress, and the insulin pathway is known to mediate oxidative damage, the goal of this research project is to evaluate the interactions of increased oxidative stress and ethanol on the survival and developmental delay of larvae reared in ethanol and paraquat treated food. Our hypothesis is that at least some of the ethanol-induced phenotypes are a result of oxidative stress and that combining ethanol exposure with a known oxidative stress-inducing agent will produce non-additive effects indicating synergy between ethanol exposure and oxidative stress. The highest dose of paraquat, which had no effect on larval survival, was combined with a concentration of ethanol which similarly had no effect on survival in fly food. Preliminary data indicate that together, paraquat and ethanol appear to increase developmental delay and decrease viability, and various insulin signaling mutants are being tested. The data suggest that some of the ethanol-induced phenotypes are indeed due to oxidative stress, and give us more information about the mediation of oxidative stress by the insulin pathway.