Effects of titanium dioxide nanoparticles on human keratinocytes

Titanium dioxide (TiO₂) is a ubiquitous whitening compound widely used in topical products such as sunscreens, lotions and facial creams. The damaging health effects of TiO₂ inhalation has been widely studied in rats, mice and humans showing oxidative stress increase, DNA damage, cell death and inflammatory gene upregulation in lung and throat cells; however, the effects on skin cells from long-term topical use of various products remain largely unknown. In this study, we assessed the effect of specific TiO₂ nanoparticles (H₂TiO₇) on a human keratinocyte cell line (HaCaT). We performed a comparative analysis using three TiO₂ particles varying in size (Fine, Ultrafine and H₂TiO₇) and analyzed their effects on HaCaTs. There is a clear dose-dependent increase in superoxide production, caspase 8 and 9 activity, and apoptosis in HaCaTs after treatment with all three forms of TiO₂; however, there is no consistent effect on cell viability and proliferation with either of these TiO₂ particles. While there is data suggesting UV exposure can enhance the carcinogenic effects of TiO₂, we did not observe any significant effect of UV-C exposure combined with TiO₂ treatment on HaCaTs. Furthermore, TiO₂-treated cells showed minimal effects on VEGF upregulation and Wnt signaling pathway thereby showing no potential effect on angiogenesis and malignant transformation. Overall, we report here an increase in apoptosis, which may be caspase 8/Fas-dependent, and that the H₂TiO₇ nanoparticles, despite their smaller particle size, had no significant enhanced effect on HaCaT cells as compared to Fine and Ultrafine forms of TiO₂.