title: In vitro proliferating cell models to study cytotoxicity of silica nanowires.
abstract: Proliferating cells representing two disease models (HeLa and Panc 10.05 cells) and a more physiologically relevant cell model (3T3-L1 cells) were used to study the acute toxicologic effects of silica nanowires (NWs). Cellular responses to NW effects were determined over a 4- to 20-hour exposure time-course. Proliferation, viability, metabolic activity, and toxicologic mechanism (apoptosis vs. necrosis) data showed the following: 3 x 10(4) NWs per cell inhibited cell proliferation. The effect was rapid in HeLa cells, but 3T3-L1 and Panc 10.05 cells appeared to be more tolerant to NWs, effects being significant only after 20 or 16 hours, respectively. Cells of all three cell lines showed a significant reduction in cellular metabolic activity after 20 hours of treatment with NWs. Assay of NW-invoked mechanism of cell death (caspase 3/7 activity) indicated that apoptosis was minimally induced. Small but significant effects of NWs were detected in 3T3-L1 and HeLa cells after 20-hour treatment. No NW-induction of caspase 3/7 activity was detected for Panc 10.05 cells. Proliferating cells provide a sensitive model to study treatment with silica NWs. Silica NWs appeared to be well tolerated by these three cell lines at the doses tested. When effects were detected, cell necrosis and not apoptosis was the main mechanism of silica NW-induced cell death.
  
  
  BACKGROUND
  In this study, three relevant cell culture models were used to study the acute toxicological effects of silica nanowires (NW). All cell lines cells showed a significant reduction in cellular metabolic activity after 20 h of treatment with NW. Overall, silica NW appeared to be well-tolerated by these cell lines at the tested doses. Cell necrosis as opposed to apoptosis was the main mechanism of silica NW-induced cell death.
authors.affiliation: Department of Animal and Veterinary Science, University of Idaho, Moscow, Idaho 83844, USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Julien
authors.forename: Casey C
authors.initials: CC
authors.lastname: Richardson
authors.forename: Miles F
authors.initials: MF
authors.lastname: Beaux
authors.forename: David N
authors.initials: DN
authors.lastname: McIlroy
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Hill
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001681:Biological Assay; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D051379:Mice; D008954:Models, Biological; D053770:Nanowires / Q000633:toxicity*; D009336:Necrosis; D012822:Silicon Dioxide / Q000633:toxicity*
chemical_list: D012822:Silicon Dioxide; D053148:Caspase 3; D053179:Caspase 7