title: Effects of structurally different noncoplanar and coplanar PCBs on HELF cell proliferation, cell cycle, and potential molecular mechanisms.
abstract: Polychlorinated biphenyls (PCBs) are a group of chemicals that persist in the environment, indoors, and humans. Lung exposure to airborne and food contaminants, such as PCBs, may cause possible lung disorders, such as cancer. In the present study, we investigated the effects of structurally different lower chlorinated (≤4Cl), noncoplanar PCB40, and coplanar PCB77 on human lung fibroblast cell line (HELF) cell proliferation, cell cycle progression, and possible molecular mechanisms. Noncoplanar PCB40 and coplanar PCB77 exhibited concentration- and time-dependent biphasic dose-response effects on HELF cell proliferation. Noncoplanar PCB40 and coplanar PCB77 induced 23 and 45% cytotoxicity at higher concentrations than the control. The flow cytometry analysis showed that exposure to PCB40 caused a significant increase in time spent in the G1 phase but decreased length of the S phase in a concentration- and time-dependent manner, whereas PCB77 exposure decreased time spent in the G1 and S phases but increased time spent in the G2 phase. Western blot analysis indicated that PCB77 increased the expression of cyclin E, CDK2, p21, and caspase-9, while PCB40 decreased the expression of these proteins (except CDK2 and p21). An increase in CDK expression after exposure to PCB77 suggests that it may cause carcinogenic effects on HELF cells at higher doses. Our results also demonstrate that the different cytotoxic effects induced by coplanar and nonplanar PCBs were correlated with their structural characteristics; the coplanar congener was more cytotoxic than the nonplanar congener. The study elaborates threshold levels for these chemicals and suggests that the cytotoxicity mechanisms by which PCB congeners act on HELF cells depend on their planarity and chemical structures. Furthermore, the study will be important for developing antidotes to the adverse effects and risk assessment practices for PCBs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1183-1190, 2017.
authors.affiliation: Department of Environmental Engineering, College of Environmental & Resource Sciences, Zhejiang University, Hangzhou, 310058, People's Republic of China.|Department of Meteorology, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: Muhammad Zaffar
authors.initials: MZ
authors.lastname: Hashmi
authors.affiliation: Department of Environmental Engineering, College of Environmental & Resource Sciences, Zhejiang University, Hangzhou, 310058, People's Republic of China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Environmental Engineering, College of Environmental & Resource Sciences, Zhejiang University, Hangzhou, 310058, People's Republic of China.
authors.forename: Binglu
authors.initials: B
authors.lastname: Li
authors.affiliation: College of Geography and Environmental Science, Zhejiang Normal University, Jinhua, 321004, People's Republic of China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Su
authors.affiliation: Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, People's Republic of China.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Tariq
authors.affiliation: School of Economics, Dongbei University of Finance and Economics, Dalian, People's Republic of China.
authors.forename: Najid
authors.initials: N
authors.lastname: Ahmad
authors.affiliation: Environmental Biology and Ecotoxicology Laboratory, Department of Environmental Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Riffat Naseem
authors.initials: RN
authors.lastname: Malik
authors.affiliation: Department of Meteorology, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: Kalim
authors.initials: K
authors.lastname: Ullah
authors.affiliation: Department of Environmental Engineering, College of Environmental & Resource Sciences, Zhejiang University, Hangzhou, 310058, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Environmental Engineering, College of Environmental & Resource Sciences, Zhejiang University, Hangzhou, 310058, People's Republic of China.
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Shen
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000166:cytology; D008968:Molecular Conformation; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D013329:Structure-Activity Relationship
chemical_list: D004785:Environmental Pollutants; D011078:Polychlorinated Biphenyls
keywords: CDK2; PCBs; cancer; cytotoxic; hormesis; human lung cell proliferation