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Metabolomic effects in HepG2 cells exposed to CeO2, SiO2 and CuO nanomaterials.
Citation:
Kitchin, K., B. Robinette, B. Castellon, AND S. Stirdivant. Metabolomic effects in HepG2 cells exposed to CeO2, SiO2 and CuO nanomaterials. 8th International Nanotoxicology Congress, Boston, MA, June 01 - 04, 2016.
Impact/Purpose:
To better assess potential hepatotoxicity of nanomaterials, human liver HepG2 cells were exposed for three days to 5 different CeO2 (either 30 or 100 ug/ml), 3 SiO2 based (30 ug/ml) or 1 CuO (3 ug/ml) nanomaterials with dry primary particle sizes ranging from 15 to 213 nm.
Description:
To better assess potential hepatotoxicity of nanomaterials, human liver HepG2 cells were exposed for three days to 5 different CeO2 (either 30 or 100 ug/ml), 3 SiO2 based (30 ug/ml) or 1 CuO (3 ug/ml) nanomaterials with dry primary particle sizes ranging from 15 to 213 nm. Metabolomic assessment of exposed cells was then performed using four mass spectroscopy dependent platforms (LC and GC), finding 344 biochemicals. Four CeO2, 1 SiO2 and 1 CuO nanomaterials increased hepatocyte concentrations of many lipids, particularly free fatty acids and monoacylglycerols but only CuO elevated lysolipids and sphingolipids. Observed decreases in UDP-glucuronate (by CeO2) and S-adenosylmethionine (by CeO2 and CuO) and increased S-adenosylhomocysteine (by CuO and some CeO2) suggest that a nanomaterial exposure increases transmethylation reactions and depletes hepatic methylation and glucuronidation capacity. There was a clear pattern of nanomaterial-induced decreased nucleotide concentrations coupled with increased concentrations of nucleic acid degradation products. An earlier observation of CeO2 induced lipid elevations has been confirmed by 4 other different CeO2 as well as SiO2 and CuO nanomaterials. Additionally some metal oxide nanomaterials induced declines in S-adenosylmethionine, UDP-glucuronate, dipeptides, 6-phosphogluconate, NADPH and NADH.