Title: Modulation of different Stress Pathways after Styrene and Styrene-7,8-oxide Exposure in HepG2 Cell Line and normal human Hepatocytes
Authors: DIODOVICH CristinaURANI ChiaraMAURICI DanielaMALERBA IlariaMELCHIORETTO PasqualeORLANDI MarcoZOIA LucaCAMPI VALENTINACARFI' MARIAPELLIZZER CRISTIANGRIBALDO LAURA
Citation: JOURNAL OF APPLIED TOXICOLOGY vol. 26 no. 4 p. 317-325
Publisher: JOHN WILEY & SONS LTD
Publication Year: 2006
JRC N°: JRC34151
URI: http://publications.jrc.ec.europa.eu/repository/handle/JRC34151
Type: Articles in Journals
Abstract: Styrene is one of the most important monomers produced worldwide. IARC classified styrene as a possible carcinogen to humans (group 2B). Styrene-7,8-oxide (SO) is the main reactive metabolite of styrene, and it is found to be genotoxic in several in vitro test systems. Styrene and styrene-7,8-oxide (SO) toxicity to HepG2 cells was investigated by evaluating end-points such as heat shock proteins (Hsps), metallothioneins (MT), apoptosis-related proteins, accumulation of styrene within the cells and expression of two isoforms of cytochrome P450. The potential activity of styrene and styrene-7,8-oxide in modulating gene expression was also investigated. The results showed induction of Hsp70, metallothioneins, BclXS/L and c-myc expression and a decrease in Bax expression in HepG2 after treatments, confirming that these compounds activated protective mechanisms. Moreover, up-regulation of TGF β2 and TGF βRIII in HepG2 cells was found after exposure to styrene, while in human primary hepatocytes these genes were down-regulated after both treatments. Finally, it was found that styrene and SO treatments did not induce CYP1A2 and CYP2E1 protein expression. In conclusion, both compounds caused toxic stress in HepG2 cells, with SO being more toxic; in the meantime, a different effect of the two compounds in HepG2 cells and primary human hepatocytes was observed regarding their activity in gene modulation.
JRC Institute:Institute for Health and Consumer Protection

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