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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.
- Source :
-
Journal of applied toxicology : JAT [J Appl Toxicol] 2006 Jul-Aug; Vol. 26 (4), pp. 317-25. - Publication Year :
- 2006
-
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, BclX(S/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 TGFbeta2 and TGFbetaRIII 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.<br /> (Copyright 2006 John Wiley & Sons, Ltd.)
- Subjects :
- Carcinogens metabolism
Carcinoma, Hepatocellular
Cell Line, Tumor
Cytochrome P-450 CYP1A2 metabolism
Cytochrome P-450 CYP2E1 metabolism
Enzyme-Linked Immunosorbent Assay
Epoxy Compounds metabolism
Gene Expression Profiling methods
Gene Expression Regulation
HSP70 Heat-Shock Proteins metabolism
Hepatocytes enzymology
Humans
Metallothionein metabolism
Oligonucleotide Array Sequence Analysis
Polymerase Chain Reaction
Proteoglycans genetics
Proteoglycans metabolism
Proto-Oncogene Proteins c-myc metabolism
RNA, Messenger metabolism
Receptors, Transforming Growth Factor beta genetics
Receptors, Transforming Growth Factor beta metabolism
Styrene metabolism
Transforming Growth Factor beta2 genetics
Transforming Growth Factor beta2 metabolism
bcl-X Protein metabolism
Carcinogens toxicity
Epoxy Compounds toxicity
Hepatocytes drug effects
Styrene toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 0260-437X
- Volume :
- 26
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of applied toxicology : JAT
- Publication Type :
- Academic Journal
- Accession number :
- 16705669
- Full Text :
- https://doi.org/10.1002/jat.1142