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Modulation of different stress pathways after styrene and styrene-7,8-oxide exposure in HepG2 cell line and normal human hepatocytes

2006; Wiley; Volume: 26; Issue: 4 Linguagem: Inglês

10.1002/jat.1142

1099-1263

Cristina Diodovich, Chiara Urani, Daniela Maurici, Ilaria Malerba, Pasquale Melchioretto, Marco Orlandi, Luca Zoia, Valentina Campi, Maria Carfì, Cristian Pellizzer, Laura Gribaldo,

Genomics, phytochemicals, and oxidative stress

Journal of Applied ToxicologyVolume 26, Issue 4 p. 317-325 Research Article Modulation of different stress pathways after styrene and styrene-7,8-oxide exposure in HepG2 cell line and normal human hepatocytes Cristina Diodovich, Cristina Diodovich ECVAM, Institute for Health and Consumer Protection, J.R.C., Ispra, ItalySearch for more papers by this authorChiara Urani, Chiara Urani Dipartimento di Scienze dell'Ambiente e del Territorio, Università degli Studi di Milano Bicocca, Milan, ItalySearch for more papers by this authorDaniela Maurici, Daniela Maurici ECVAM, Institute for Health and Consumer Protection, J.R.C., Ispra, ItalySearch for more papers by this authorIlaria Malerba, Ilaria Malerba ECVAM, Institute for Health and Consumer Protection, J.R.C., Ispra, ItalySearch for more papers by this authorPasquale Melchioretto, Pasquale Melchioretto Dipartimento di Scienze dell'Ambiente e del Territorio, Università degli Studi di Milano Bicocca, Milan, ItalySearch for more papers by this authorMarco Orlandi, Marco Orlandi Dipartimento di Scienze dell'Ambiente e del Territorio, Università degli Studi di Milano Bicocca, Milan, ItalySearch for more papers by this authorLuca Zoia, Luca Zoia Dipartimento di Scienze dell'Ambiente e del Territorio, Università degli Studi di Milano Bicocca, Milan, ItalySearch for more papers by this authorValentina Campi, Valentina Campi ECVAM, Institute for Health and Consumer Protection, J.R.C., Ispra, ItalySearch for more papers by this authorMaria Carfi', Maria Carfi' ECVAM, Institute for Health and Consumer Protection, J.R.C., Ispra, ItalySearch for more papers by this authorCristian Pellizzer, Cristian Pellizzer ECVAM, Institute for Health and Consumer Protection, J.R.C., Ispra, ItalySearch for more papers by this authorLaura Gribaldo, Corresponding Author Laura Gribaldo laura.gribaldo@jrc.it ECVAM, Institute for Health and Consumer Protection, J.R.C., Ispra, ItalyLaboratory of Hematotoxicology, ECVAM, Institute for Health and Consumer Protection, J.R.C., Ispra 21020, Italy.Search for more papers by this author Cristina Diodovich, Cristina Diodovich ECVAM, Institute for Health and Consumer Protection, J.R.C., Ispra, ItalySearch for more papers by this authorChiara Urani, Chiara Urani Dipartimento di Scienze dell'Ambiente e del Territorio, Università degli Studi di Milano Bicocca, Milan, ItalySearch for more papers by this authorDaniela Maurici, Daniela Maurici ECVAM, Institute for Health and Consumer Protection, J.R.C., Ispra, ItalySearch for more papers by this authorIlaria Malerba, Ilaria Malerba ECVAM, Institute for Health and Consumer Protection, J.R.C., Ispra, ItalySearch for more papers by this authorPasquale Melchioretto, Pasquale Melchioretto Dipartimento di Scienze dell'Ambiente e del Territorio, Università degli Studi di Milano Bicocca, Milan, ItalySearch for more papers by this authorMarco Orlandi, Marco Orlandi Dipartimento di Scienze dell'Ambiente e del Territorio, Università degli Studi di Milano Bicocca, Milan, ItalySearch for more papers by this authorLuca Zoia, Luca Zoia Dipartimento di Scienze dell'Ambiente e del Territorio, Università degli Studi di Milano Bicocca, Milan, ItalySearch for more papers by this authorValentina Campi, Valentina Campi ECVAM, Institute for Health and Consumer Protection, J.R.C., Ispra, ItalySearch for more papers by this authorMaria Carfi', Maria Carfi' ECVAM, Institute for Health and Consumer Protection, J.R.C., Ispra, ItalySearch for more papers by this authorCristian Pellizzer, Cristian Pellizzer ECVAM, Institute for Health and Consumer Protection, J.R.C., Ispra, ItalySearch for more papers by this authorLaura Gribaldo, Corresponding Author Laura Gribaldo laura.gribaldo@jrc.it ECVAM, Institute for Health and Consumer Protection, J.R.C., Ispra, ItalyLaboratory of Hematotoxicology, ECVAM, Institute for Health and Consumer Protection, J.R.C., Ispra 21020, Italy.Search for more papers by this author First published: 16 May 2006 https://doi.org/10.1002/jat.1142Citations: 9AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat 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 TGFβ2 and TGFβRIII 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. Copyright © 2006 John Wiley & Sons, Ltd. Citing Literature Volume26, Issue4July/August 2006Pages 317-325 RelatedInformation