High-throughput identification of oxidative stress-inducing environmental chemicals in the C. elegans system

The metabolism of xenobiotic chemicals from the environment can produce reactive oxygen species leading to oxidative stress that is detrimental to the cell. To study the environmental factors that influence oxidative stress, we employed C. elegans engineered with a GFP tagged to the glutathione s-transferase 4 gene encoding a phase II enzyme as a biomarker for oxidative stress to screen against the U.S. EPA Toxcast library containing 4665 unique chemicals. We identified 49 chemicals that induced oxidative stress, as indicated by an increase in gst-4p::GFP signal. Quantitative PCR was used to measure the changes in mRNA expression corresponding to phase II detoxification enzymes to confirm the induction of oxidative stress for the top 10 chemicals. Among these chemicals include pesticides such as tepraloxydim, dichlone, pentachloronitrobenzene, and common industrial reagents such as ethyl acrylate and dinitrochlorobenzene. Overall, this study presents a comprehensive screening and identification of environmentally relevant chemicals that pose potential cellular toxicity as inducers of oxidative stress.