title: Deducing in vivo toxicity of combustion-derived nanoparticles from a cell-free oxidative potency assay and metabolic activation of organic compounds.
abstract: BACKGROUND
  The inhalation of combustion-derived nanoparticles (CDNPs) is believed to cause an oxidative stress response, which in turn may lead to pulmonary or even systemic inflammation.
  
  
  OBJECTIVE
  In this study we assessed whether the in vivo inflammatory response--which is generally referred to as particle toxicity-of mice to CDNPs can be predicted in vitro by a cell-free ascorbate test for the surface reactivity or, more precisely, oxidative potency (OxPot) of particles.
  
  
  RESULTS
  For six types of CDNPs with widely varying particle diameter (10-50 nm), organic content (OC; 1-20%), and specific Brunauer, Emmett, and Teller (BET) surface area (43-800 m2/g), OxPot correlated strongly with the in vivo inflammatory response (pulmonary polymorphonuclear neutrophil influx 24 hr after intratracheal particle instillation). However, for CDNPs with high organic content, OxPot could not explain the observed inflammatory response, possibly due to shielding of the OxPot of the carbon core of CDNPs by an organic coating. On the other hand, a pathway-specific gene expression screen indicated that, for particles rich in polycyclic aromatic hydrocarbon (PAHs), cytochrome P450 1A1 (CYP1A1) enzyme-mediated biotransformation of bio-available organics may generate oxidative stress and thus enhance the in vivo inflammatory response.
  
  
  CONCLUSIONS
  The compensatory nature of both effects (shielding of carbon core and biotransformation of PAHs) results in a good correlation between inflammatory response and BET surface area for all CDNPs. Hence, the in vivo inflammatory response can either be predicted by BET surface area or by a simple quantitative model, based on in vitro OxPot and Cyp1a1 induction.
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Inhalation Biology, Neuherberg/Munich, Germany. tobias.stoeger@helm-holtz-muenchen.de
authors.forename: Tobias
authors.initials: T
authors.lastname: Stoeger
authors.forename: Shinji
authors.initials: S
authors.lastname: Takenaka
authors.forename: Birgit
authors.initials: B
authors.lastname: Frankenberger
authors.forename: Baerbel
authors.initials: B
authors.lastname: Ritter
authors.forename: Erwin
authors.initials: E
authors.lastname: Karg
authors.forename: Konrad
authors.initials: K
authors.lastname: Maier
authors.forename: Holger
authors.initials: H
authors.lastname: Schulz
authors.forename: Otmar
authors.initials: O
authors.lastname: Schmid
mesh_terms: D000818:Animals; D001711:Biotransformation; D002474:Cell-Free System; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D009930:Organic Chemicals / Q000493:pharmacokinetics*; D010084:Oxidation-Reduction
chemical_list: D009930:Organic Chemicals