Organic Extract Contaminants from Drinking Water Activate Nrf2-Mediated Antioxidant Response in a Human Cell Line

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• 作者：Shu Wang ; Hao Zhang ; Weiwei Zheng ; Xia Wang ; Melvin E. Andersen ; Jingbo Pi ; Gengsheng He ; Weidong Qu
• 刊名：Environmental Science & Technology (ES&T)
• 出版年：2013
• 出版时间：May 7, 2013
• 年：2013
• 卷：47
• 期：9
• 页码：4768-4777
• 全文大小：419K
• 年卷期：v.47,no.9(May 7, 2013)
• ISSN：1520-5851

文摘

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鈥攎easured 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.