Fan Rui-Mei, Zhu Ben-Zhan, Huang Chin-Pao, Sheng Zhi-Guo, Mao Li, Li Ming-Xin
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.
Environmental Engineering, Civil and Environmental Engineering Department, University of Delaware, USA.
Environ Toxicol. 2016 Dec;31(12):1964-1973. doi: 10.1002/tox.22197. Epub 2015 Sep 29.
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 /G 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.
甲拌磷和含铜/锌的化合物都被广泛用作杀菌剂。因此，它们可能会在生物圈中同时出现。尽管已经对甲拌磷或铜（II）/锌（II）的单独毒性进行了某些研究，但它们的协同毒性尚未得到研究。在本文中，当无毒和亚毒性水平的甲拌磷与铜（II）/锌（II）组合时，在HepG2细胞中观察到了显著的协同毒性。出乎意料的是，甲拌磷/铜（II）和甲拌磷/锌（II）之间的细胞死亡模式不同：对于甲拌磷/铜（II），从包括细胞质-染色质浓缩、磷脂酰丝氨酸（PS）暴露、亚G1/G0 DNA片段化、线粒体膜电位降低、促凋亡/抗凋亡蛋白激活和细胞色素c释放等形态学特征可以明显看出凋亡；对于甲拌磷/锌（II），从细胞器肿胀和不受控制的崩溃可以明显看出坏死。据我们所知，这项工作不仅首次证明了甲拌磷与铜（II）/锌（II）的协同毒性，还验证了甲拌磷/铜（II）和甲拌磷/锌（II）之间凋亡/坏死的不同模式。© 2015威利期刊公司。《环境毒理学》31: 1964 - 1973, 2016。
