Carbon nanotube translocation to distant organs after pulmonary exposure: insights from in situ (14)C-radiolabeling and tissue radioimaging.
Few approaches are available to investigate the potential of carbon nanotubes (CNTs) to translocate to distant organs following lung exposure, although this needs to be taken into account to evaluate potential CNT toxicity. Here, we report a method for quantitative analysis of the tissue biodistribution of multiwalled CNTs (MWCNTs) as a function of time. The method relies on the use of in situ (14)C-radiolabeled MWCNTs and combines radioimaging of organ tissue sections to ex vivo analysis of MWCNTs by electron microscopy. To illustrate the usefulness of this approach, mice were exposed to a single dose of 20 μg of (14)C-labeled MWCNTs by pharyngeal aspiration and were subjected to a follow-up study over one year. After administration, MWCNT were cleared from the lungs, but there was a concomitant relocation of these nanoparticles to distant organs starting throughout the follow-up period, with nanoparticle accumulation increasing with time. After one year, accumulation of MWCNTs was documented in several organs, including notably the white pulp of the spleen and the bone marrow. This study shows that the proposed method may be useful to complement other approaches to address unresolved toxicological issues associated with CNTs. These issues include their persistence over long periods in extrapulmonary organs, the relationship between the dose and the extent of translocation, and the effects of "safety by design" on those processes. The same approach could be used to study the translocation propensity of other nanoparticles containing carbon atoms.
CEA-Saclay, Service d'Ingénierie Moléculaire des Protéines, Labex LERMIT, CEA-DSV-iBiTecS , 91191 Gif/Yvette, France.
Bertrand
B
Czarny
Dominique
D
Georgin
Fannely
F
Berthon
Gael
G
Plastow
Mathieu
M
Pinault
Gilles
G
Patriarche
Aurélie
A
Thuleau
Martine Mayne
MM
L'Hermite
Frédéric
F
Taran
Vincent
V
Dive
D000388:Air; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002250:Carbon Radioisotopes / Q000737:chemistry*; D002855:Chromatography, Thin Layer; D004305:Dose-Response Relationship, Drug; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D036103:Nanotechnology / Q000379:methods*; D037742:Nanotubes, Carbon / Q000737:chemistry*; D053120:Respiratory Aspiration; D012588:Scintillation Counting; D013154:Spleen / Q000187:drug effects; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D037742:Nanotubes, Carbon