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Different modes of synergistic toxicities between metam/copper (II) and metam/zinc (II) in HepG2 cells: apoptosis vs. necrosis
Authors:Rui‐mei Fan  Ben‐zhan Zhu  Chin‐pao Huang  Zhi‐guo Sheng  Li Mao  Ming‐xin Li
Affiliation:1. State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco‐Environmental Sciences, Chinese Academy of Sciences, Beijing, China;2. Environmental Engineering, Civil and Environmental Engineering Department, University of Delaware, USA
Abstract:Both metam sodium and copper/zinc‐containing compounds are widely used as fungicides. They therefore may co‐occur in the biosphere. Despite certain studies of individual toxicity for either metam or copper (II)/zinc (II), their synergistic toxicity has not been examined. In this paper, a remarkable synergistic toxicity was observed in HepG2 cells when metam and copper (II)/zinc (II) at non‐toxic and sub‐toxic levels were combined. Unexpectedly, cell death modes between metam/copper (II) and metam/zinc (II) were different: For metam/copper (II), apoptosis was evident from morphological characteristics including cytoplasm‐chromatin condensation, phosphatidylserine (PS) exposure, SubG0/G1 DNA fragmentation, mitochondrial membrane potential decrease, pro/anti‐apoptotic protein activation, and cytochrome c release; for metam/zinc (II), necrosis was evident from organelle swelling and uncontrolled collapse. To our knowledge, this work first not only demonstrates the synergistic toxicities of metam and both copper (II)/zinc (II), but also verifies the different modes of apoptosis/necrosis between metam/copper (II) and metam/zinc (II). © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1964–1973, 2016.
Keywords:metam  copper (II)  zinc (II)  synergistic toxicity  apoptosis  necrosis
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