You are here:
Differential genomic effects of six different TiO2 nanomaterials on human liver HepG2 cells
Thai, S., K. Wallace, C. Jones, H. Ren, J. Crooks, K. Kitchin, B. Castellon, AND E. Grulke. Differential genomic effects of six different TiO2 nanomaterials on human liver HepG2 cells. JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY. John Wiley & Sons, Ltd., Indianapolis, IN, 0(0):331-341, (2016).
Many in vivo studies show that NPs accumulate in the liver, kidney, spleen, lung, heart and brain; generate various inflammatory responses in mice; and induce liver toxicity. In one of the studies, liver damage was observed after intraperitoneal injection. The oral exposure route is important because nano-TiO2 is widely used as a food additive, in toothpaste and capsules. This in vitro, genomic study revealed some possible mechanisms through which nanoparticles caused liver toxicity in vivo.
Engineered nanoparticles are reported to cause liver toxicity in vivo. To better assess the mechanism of the in vivo liver toxicity, we used the human hepatocarcinoma cells (HepG2) as a model system. Human HepG2 cells were exposed to 6 TiO2 nanomaterials (with dry primary particle sizes ranging from 22 to 214 nm, either 0.3, 3 or 30 g/ml) for three days. In culture media with 10% fetal bovine serum the hydrodynamic sizes ranged from 328 to 534 nm. With respect to physical-chemical characteristics, hydrodynamic agglomerated particle size rather than dry particle size or surface area correlated best with our biological and genomic outcomes. Even though all six NPs are composed of TiO2, they elicited fairly different canonical pathway responses. Some of these canonical pathways changed by nano-TiO2 in vitro treatments have been already reported in literature, such as NRF2-mediated stress response, fatty acid metabolism, cell cycle and apoptosis, immune response, cholesterol biosynthesis and glycolysis. But this genomic study also revealed some novel effects such as protein synthesis, protein ubiquitination, hepatic fibrosis and cancer related signaling pathways. More importantly, this genomic analysis of HepG2 cells treated with 6 nano-TiO2 linked some of the in vitro canonical pathways to in vivo adverse outcomes, e.g., NRF2 mediated response pathways to oxidative stress, acute phase response to inflammation, cholesterol biosynthesis to steroid hormones alteration, fatty acid metabolism changes to lipid homeostasis alteration, G2/M cell checkpoint regulation to apoptosis and hepatic fibrosis/stellate cell activation to liver fibrosis. This study revealed some possible mechanisms through which nanoparticles caused liver toxicity in vivo.
HEPG2 TIO2 PAPER REVISION2.PDF (PDF,NA pp, 7090.288 KB, about PDF)
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
INTEGRATED SYSTEMS TOXICOLOGY DIVISION
SYSTEMS BIOLOGY BRANCH