title: Comparison of Cytotoxicity and Inhibition of Membrane ABC Transporters Induced by MWCNTs with Different Length and Functional Groups.
abstract: Experimental studies indicate that multiwalled carbon nanotubes (MWCNTs) have the potential to induce cytotoxicity. However, the reports are often inconsistent and even contradictory. Additionally, adverse effects of MWCNTs at low concentration are not well understood. In this study, we systemically compared adverse effects of six MWCNTs including pristine MWCNTs, hydroxyl-MWCNTs and carboxyl-MWCNTs of two different lengths (0.5-2 μm and 10-30 μm) on human hepatoma cell line HepG2. Results showed that MWCNTs induced cytotoxicity by increasing reactive oxygen species (ROS) generation and damaging cell function. Pristine short MWCNTs induced higher cytotoxicity than pristine long MWCNTs. Functionalization increased cytotoxicity of long MWCNTs, but reduced cytotoxicity of short MWCNTs. Further, our results indicated that the six MWCNTs, at nontoxic concentration, might not be environmentally safe as they inhibited ABC transporters' efflux capabilities. This inhibition was observed even at very low concentrations, which were 40-1000 times lower than their effective concentrations on cytotoxicity. The inhibition of ABC transporters significantly increased cytotoxicity of arsenic, a known substrate of ABC transporters, indicating a chemosensitizing effect of MWCNTs. Plasma membrane damage was likely the mechanism by which the six MWCNTs inhibited ABC transporter activity. This study provides insight into risk assessments of low levels of MWCNTs in the environment.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University , Nanjing, 210023, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University , Nanjing, 210023, P.R. China.
authors.forename: Su
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University , Nanjing, 210023, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University , Nanjing, 210023, P.R. China.
authors.forename: Zhuoyan
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Bodega Marine Laboratory, University of California , Davis, California United States.|Departments of Environmental Toxicology and Nutrition, University of California , Davis, California United States.
authors.forename: Gary N
authors.initials: GN
authors.lastname: Cherr
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University , Nanjing, 210023, P.R. China.
authors.forename: Xu-Xiang
authors.initials: XX
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University , Nanjing, 210023, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D005452:Fluoresceins / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D005452:Fluoresceins; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species; C085925:calcein AM