title: Combined toxicity and underlying mechanisms of a mixture of eight heavy metals.
abstract: With the rapid development of modernization and industrialization in China, a large quantity of heavy metals, including zinc, copper, lead, cadmium and mercury, have been entering the atmosphere, soil and water, the latter being the primary route of pollution. In the present study, in vitro experiments were performed to examine the joint toxicity and the underlying mechanisms of the eight most common heavy metals contaminating offshore waters on the eastern coast of Ningbo region. Using a cell cycle assay, cell apoptosis and reactive oxygen species (ROS) detection methods, the present study demonstrated that the heavy metal mixture arrested JB6 cells at the S phase, induced the generation of ROS and cell apoptosis. A luciferase assay indicated that the levels of activator protein‑1 and nuclear factor‑κB transcription factors were upregulated. Upregulation of the protein levels of C‑jun and p65 were detected in the JB6 cells by western blot analysis; these two genes have important roles in cell carcinogenesis. These results provide a useful reference for further investigations on the combined toxicity of the exposure to multiple heavy metals.
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Yuanliang
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Yue
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Guochuan
authors.initials: G
authors.lastname: Mao
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Baobo
authors.initials: B
authors.lastname: Zou
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Jinshun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Renyuan
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D003603:Cytotoxins / Q000633:toxicity; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019216:Metals, Heavy / Q000633:toxicity*; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D003603:Cytotoxins; D019216:Metals, Heavy; D017382:Reactive Oxygen Species; D014874:Water Pollutants, Chemical