title: Organic extract contaminants from drinking water activate Nrf2-mediated antioxidant response in a human cell line.
abstract: Traditional risk assessment methods face challenges in estimating risks from drinking waters that contain low-levels of large numbers of contaminants. Here, we evaluate the toxicity of organic contaminant (OC) extracts from drinking water by examining activation of nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant response. In HepG2 cells, the Nrf2-mediated antioxidant response-measured as Nrf2 protein accumulation, expression of antioxidant response element (ARE)-regulated genes and ARE-luciferase reporter gene assays were activated by OC extracts from drinking water sources that detected 25 compounds in 9 classification groups. Individual OCs induced oxidative stress at concentrations much higher than their environmental levels; however, mixtures of contaminants induced oxidative stress response at only 8 times the environmental levels. Additionally, a synthetic OC mixture prepared based on the contamination profiling of drinking water induced ARE activity to the same extent as the real-world mixture, reinforcing our conclusion that these mixture exposures produce responses relevant for human exposure situations. Our study tested the possibility of assessing toxicity of OCs of drinking water using a specific ARE-pathway measurement. This approach should be broadly useful in assisting risk assessment of mixed environmental exposure.
authors.affiliation: Key Laboratory of the Public Health Safety, Ministry of Education, Department of Environmental Health, School of Public Health, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zheng
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Melvin E
authors.initials: ME
authors.lastname: Andersen
authors.forename: Jingbo
authors.initials: J
authors.lastname: Pi
authors.forename: Gengsheng
authors.initials: G
authors.lastname: He
authors.forename: Weidong
authors.initials: W
authors.lastname: Qu
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D060766:Drinking Water / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014874:Water Pollutants, Chemical / Q000302:isolation & purification* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D060766:Drinking Water; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D014874:Water Pollutants, Chemical