title: Metabolic effects of TiO2 nanoparticles, a common component of sunscreens and cosmetics, on human keratinocytes.
abstract: The long-term health risks of nanoparticles remain poorly understood, which is a serious concern given their prevalence in the environment from increased industrial and domestic use. The extent to which such compounds contribute to cellular toxicity is unclear, and although it is known that induction of oxidative stress pathways is associated with this process, the proteins and the metabolic pathways involved with nanoparticle-mediated oxidative stress and toxicity are largely unknown. To investigate this problem further, the effect of TiO2 on the HaCaT human keratinocyte cell line was examined. The data show that although TiO2 does not affect cell cycle phase distribution, nor cell death, these nanoparticles have a considerable and rapid effect on mitochondrial function. Metabolic analysis was performed to identify 268 metabolites of the specific pathways involved and 85 biochemical metabolites were found to be significantly altered, many of which are known to be associated with the cellular stress response. Importantly, the uptake of nanoparticles into the cultured cells was restricted to phagosomes, TiO2 nanoparticles did not enter into the nucleus or any other cytoplasmic organelle. No other morphological changes were detected after 24-h exposure consistent with a specific role of mitochondria in this response.
authors.affiliation: Medical Research Council, Toxicology Unit, Leicester University, Leicester, UK. paola.tucci@unical.it
authors.forename: P
authors.initials: P
authors.lastname: Tucci
authors.forename: G
authors.initials: G
authors.lastname: Porta
authors.forename: M
authors.initials: M
authors.lastname: Agostini
authors.forename: D
authors.initials: D
authors.lastname: Dinsdale
authors.forename: I
authors.initials: I
authors.lastname: Iavicoli
authors.forename: K
authors.initials: K
authors.lastname: Cain
authors.forename: A
authors.initials: A
authors.lastname: Finazzi-Agró
authors.forename: G
authors.initials: G
authors.lastname: Melino
authors.forename: A
authors.initials: A
authors.lastname: Willis
mesh_terms: D001692:Biological Transport; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003358:Cosmetics / Q000737:chemistry; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D018384:Oxidative Stress; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D013473:Sunscreening Agents / Q000737:chemistry; D014025:Titanium / Q000494:pharmacology*
chemical_list: D003358:Cosmetics; D017382:Reactive Oxygen Species; D013473:Sunscreening Agents; C009495:titanium dioxide; D014025:Titanium