title: Titanium dioxide nanoparticles produce phototoxicity in the developing zebrafish.
abstract: Exposure of humans and other organisms to nanomaterials is increasing exponentially. It is important, but difficult, to predict the biological consequences of these exposures. We hypothesized that the unique chemical properties that make nanoparticles useful might also be the key in predicting their biological impact. To investigate this, we chose titanium dioxide nanoparticles (TiO(2)NPs) and developing zebrafish embryos as model systems. TiO(2)NPs absorb photons to generate electron-hole pairs that react with water and oxygen to form cytotoxic reactive oxygen species (ROS). Here, we show that the exposure of zebrafish embryos to TiO(2)NPs produces malformation and death, but only if the fish are also illuminated. TiO(2)NPs are taken up into the developing fish, but the egg chorion is a barrier to uptake until the embryos hatch. Chemical probes and a transgenic reporter line confirm photo-dependent production of ROS in vivo, and the addition of an ROS scavenger rescues fish embryos from toxicity. To our knowledge, this is the first study to show a photo-dependent toxic response in a whole organism from exposure to TiO(2)NPs. Of further significance, our study highlights the relationship between the property of the material that makes it useful and the biological effect that is produced. This concept should serve as a guide for future nanotoxicological studies aiming to identify potential hazardous effects on organisms.
authors.affiliation: Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705-2222, USA.
authors.forename: Ofek
authors.initials: O
authors.lastname: Bar-Ilan
authors.forename: Kacie M
authors.initials: KM
authors.lastname: Louis
authors.forename: Sarah P
authors.initials: SP
authors.lastname: Yang
authors.forename: Joel A
authors.initials: JA
authors.lastname: Pedersen
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hamers
authors.forename: Richard E
authors.initials: RE
authors.lastname: Peterson
authors.forename: Warren
authors.initials: W
authors.lastname: Heideman
mesh_terms: D000818:Animals; D002823:Chorion / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D053768:Metal Nanoparticles / Q000528:radiation effects / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D013472:Sunlight; D016019:Survival Analysis; D014025:Titanium / Q000493:pharmacokinetics / Q000528:radiation effects / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology*
chemical_list: D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium