title: Nanoparticles can cause DNA damage across a cellular barrier.
abstract: The increasing use of nanoparticles in medicine has raised concerns over their ability to gain access to privileged sites in the body. Here, we show that cobalt-chromium nanoparticles (29.5 +/- 6.3 nm in diameter) can damage human fibroblast cells across an intact cellular barrier without having to cross the barrier. The damage is mediated by a novel mechanism involving transmission of purine nucleotides (such as ATP) and intercellular signalling within the barrier through connexin gap junctions or hemichannels and pannexin channels. The outcome, which includes DNA damage without significant cell death, is different from that observed in cells subjected to direct exposure to nanoparticles. Our results suggest the importance of indirect effects when evaluating the safety of nanoparticles. The potential damage to tissues located behind cellular barriers needs to be considered when using nanoparticles for targeting diseased states.
authors.affiliation: Bristol Implant Research Centre, Southmead Hospital, Bristol, UK.
authors.forename: Gevdeep
authors.initials: G
authors.lastname: Bhabra
authors.forename: Aman
authors.initials: A
authors.lastname: Sood
authors.forename: Brenton
authors.initials: B
authors.lastname: Fisher
authors.forename: Laura
authors.initials: L
authors.lastname: Cartwright
authors.forename: Margaret
authors.initials: M
authors.lastname: Saunders
authors.forename: William Howard
authors.initials: WH
authors.lastname: Evans
authors.forename: Annmarie
authors.initials: A
authors.lastname: Surprenant
authors.forename: Gloria
authors.initials: G
authors.lastname: Lopez-Castejon
authors.forename: Stephen
authors.initials: S
authors.lastname: Mann
authors.forename: Sean A
authors.initials: SA
authors.lastname: Davis
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Hails
authors.forename: Eileen
authors.initials: E
authors.lastname: Ingham
authors.forename: Paul
authors.initials: P
authors.lastname: Verkade
authors.forename: Jon
authors.initials: J
authors.lastname: Lane
authors.forename: Kate
authors.initials: K
authors.lastname: Heesom
authors.forename: Roger
authors.initials: R
authors.lastname: Newson
authors.forename: Charles Patrick
authors.initials: CP
authors.lastname: Case
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D045744:Cell Line, Tumor; D002857:Chromium / Q000633:toxicity; D003035:Cobalt / Q000633:toxicity; D017630:Connexins / Q000378:metabolism; D004249:DNA Damage; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D053758:Nanoparticles / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects; D014168:Transferrin / Q000378:metabolism
chemical_list: D017630:Connexins; D014168:Transferrin; D002857:Chromium; D003035:Cobalt; D000255:Adenosine Triphosphate