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Different modes of synergistic toxicities between metam/copper (II) and metam/zinc (II) in HepG2 cells: apoptosis vs. necrosis
Author(s) -
Fan Ruimei,
Zhu Benzhan,
Huang Chinpao,
Sheng Zhiguo,
Mao Li,
Li Mingxin
Publication year - 2016
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22197
Subject(s) - zinc , copper , toxicity , necrosis , apoptosis , copper toxicity , chemistry , programmed cell death , dna fragmentation , biology , biochemistry , genetics , organic chemistry
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, SubG 0 /G 1 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.