%0 Journal Article
%A Hercog, Klara
%A Maisanaba, Sara
%A Filipic, Metka
%A Sollner-Dolenc, Marija
%A Kac, Lidija
%A Zegura, Bojana
%T Genotoxic activity of bisphenol A and its analogues bisphenol S, bisphenol F and bisphenol AF and their mixtures in human hepatocellular carcinoma (HepG2) cells
%D 2019
%U https://hdl.handle.net/10433/19701
%X The use of bisphenol A (BPA) in manufacturing of plastics is being gradually replaced by presumably safer analoguessuch as bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF). Despite their widespread occurrencein the environment, there is a knowledge gap in their toxicological profiles. We investigated cytotoxic/genotoxic effects as well as changes in the expression of selected genes involved in the xenobiotic metabolism,response to oxidative stress and DNA damage upon exposure to BPs and their mixtures in human hepatocellularcarcinoma HepG2 cells.BPS and BPF slightly decreased the viability of HepG2 cells,while BPAF was the most cytotoxic compound tested.BPA, BPF and BPAF induced the formation of DNA double strand breaks determinedwith γH2AX assay,while BPSwas inactive (5–20 μg/mL). All four BPs up-regulated the expression of CYP1A1 and UGT1A1, while BPS upregulatedand BPAF down-regulated also the expression of GST1A. Only BPA up-regulated oxidative stress responsivegene GCLC, while BPAF up-regulated the expression of CDKN1A and GADD45a.At concentrations relevant for human exposure (ng/mL range) BPA and its analogues as individual compoundsand in mixtures did not exert genotoxic activity, whereas BPA and BPAF as well as the mixtures up-regulatedthe expressions of CYP1A1 and UGT1A1.
%K Bisphenol A, Bisphenol A analogues, Genotoxic, Gene expression, Combined exposure
%~