title: Mechanism of cationic phosphorus dendrimer toxicity against murine neural cell lines.
abstract: The purpose of this manuscript is to study the toxic responses against murine embryonic hippocampal cells (mHippoE-18) and neuroblastoma cells (N2a) to treatment with cationic phosphorus dendrimers (CPD). Two low generations of CPD--generation 2 (G2) and generation 3 (G3)--were applied to cell cultures to monitor events leading to either apoptosis or necrosis. These processes were analyzed using several bioassays, which included the detection of reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm) alterations, morphology changes, apoptotic and dead cells, cytochrome c (Cyt c) release, caspase 3 activity, DNA fragmentation, as well as changes in cell cycle phases distribution. The results showed that CPD became highly cytotoxic at concentrations above 1 μM and at 0.7 μM in the case of G3 for mHippoE-18 cells. The toxicity was manifested by a pronounced decrease in cell viability, which is correlated with disturbances in cellular activities, such as massive ROS generation. The breakdown of cellular processes leads mainly to the necrotic cell death. Our findings are of high importance in the context of further biomedical studies on CPD.
authors.affiliation: Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz , Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Lazniewska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Milowska
authors.forename: Maria
authors.initials: M
authors.lastname: Zablocka
authors.forename: Serge
authors.initials: S
authors.lastname: Mignani
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Caminade
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Majoral
authors.forename: Maria
authors.initials: M
authors.lastname: Bryszewska
authors.forename: Teresa
authors.initials: T
authors.lastname: Gabryelak
mesh_terms: D000818:Animals; D002412:Cations / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D005434:Flow Cytometry; D051379:Mice; D009336:Necrosis / Q000139:chemically induced; D017553:Phosphorus Compounds / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D002412:Cations; D050091:Dendrimers; D017553:Phosphorus Compounds; D017382:Reactive Oxygen Species