Metabolic effects of TiO2 nanoparticles, a common component of sunscreens and cosmetics, on human keratinocytes

The long-term health risks of nanoparticles remain poorly understood, which is a serious concern given their prevalence in theenvironment from increased industrial and domestic use. The extent to which such compounds contribute to cellular toxicity isunclear, and although it is known that induction of oxidative stress pathways is associated with this process, the proteins andthe metabolic pathways involved with nanoparticle-mediated oxidative stress and toxicity are largely unknown. To investigatethis problem further, the effect of TiO2 on the HaCaT human keratinocyte cell line was examined. The data show that althoughTiO2 does not affect cell cycle phase distribution, nor cell death, these nanoparticles have a considerable and rapid effect onmitochondrial function. Metabolic analysis was performed to identify 268 metabolites of the specific pathways involved and 85biochemical metabolites were found to be significantly altered, many of which are known to be associated with the cellular stressresponse. Importantly, the uptake of nanoparticles into the cultured cells was restricted to phagosomes, TiO2 nanoparticles didnot enter into the nucleus or any other cytoplasmic organelle. No other morphological changes were detected after 24-hexposure consistent with a specific role of mitochondria in this response.