In vitro toxicity screening of chemical mixtures using HepG2/C3A cells

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• 作者：Omari J. Bandele^a ; ^{omari.bandele@fda.hhs.gov} ; ^{ojbandele@gmail.com} ; Michael F. Santillo^a ; Martine Ferguson^b ; Paddy L. Wiesenfeld^a
• 关键词：DCF ; dichlorofluorescein ; DCFDA ; dihydrodichlorofluorescein diacetate ; DMEM ; Dulbecco&rsquo ; s modified Eagle&rsquo ; s medium ; DOSS ; diocytl sodium sulfosuccinate ; EROD ; ethoxyresorufin-O-deethylase ; FCCP ; carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazon
• 刊名：Food and Chemical Toxicology
• 出版年：2012
• 期刊代码：20_02786915
• 类别：pha
• 出版时间：May, 2012
• 卷：50
• 期：5
• 页码：1653-1659
• 文件大小：799 K

摘要

Traditional toxicological methods that utilize only single pure compounds may not accurately predict risks from substances with multiple chemical constituents. A complementary approach to conventional methodologies includes in vitro systems that assess toxicity of chemical mixtures and identify components that may adversely impact biological processes. Compared to animal models, in vitro assays are inexpensive, rapid, and reduce and refine related animal testing. We utilized HepG2/C3A cells as a hepatotoxicity screening model to evaluate the cytotoxic and metabolic effects of three commercially available oil dispersants, Corexit EC9500A and EC9527A and ZI-400. The surfactant DOSS, a primary active constituent of the Corexit dispersants, was also evaluated. Biologically relevant endpoints were measured including cell viability, oxidative stress, and mitochondrial activity. Significant increases in cytotoxicity were observed with Corexit dispersants (LC₅₀鈭?50 ppm), whereas ZI-400 was moderately cytotoxic (LC₅₀ >>400 ppm). Each dispersant caused an accumulation of reactive oxygen species and altered mitochondrial activity and other cellular processes. Generally, DOSS made notable contributions to the effects of EC9500A and EC9527A, however, they were observed at concentrations higher than those used in most consumer products. Overall, this system may represent a valuable complementary tool for predicting the toxicity of complex mixtures.