Effects of titanium dioxide nanoparticles on human keratinocytes.

Titanium dioxide (TiO) is a ubiquitous whitening compound widely used in topical products such as sunscreens, lotions and facial creams. The damaging health effects of TiO 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 TiO nanoparticles (HTiO) on a human keratinocyte cell line (HaCaT). We performed a comparative analysis using three TiO particles varying in size (Fine, Ultrafine and HTiO) 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 TiO; however, there is no consistent effect on cell viability and proliferation with either of these TiO particles. While there is data suggesting UV exposure can enhance the carcinogenic effects of TiO, we did not observe any significant effect of UV-C exposure combined with TiO treatment on HaCaTs. Furthermore, TiO-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 HTiO nanoparticles, despite their smaller particle size, had no significant enhanced effect on HaCaT cells as compared to Fine and Ultrafine forms of TiO.