Response of human cord blood cells to styrene exposure: evaluation of its effects on apoptosis and gene expression by genomic technology.
Styrene is one of the most important monomers produced worldwide, and it finds major use in the production of polystyrene, acrylonitrile-butadiene-styrene resins and unsaturated polystyrene resins. Epidemiological studies on styrene showed that the malignancies observed most frequently in humans after exposure are related to the lymphatic and haemopoietic system. IARC classified styrene a possible carcinogenic to humans (Group 2B). In this study, we evaluated the effect of styrene on gene expression profiles of human cord blood cells, as well as its activity on the apoptosis and bcl-2 related protein expression. Data demonstrated that, after 24 and 48 h of exposure, styrene (800 microM) induced an increase in the necrosis of mononuclear cord blood cells, whereas it did not cause any increase in the apoptotic process. Western blot analysis revealed a modified expression of Bax, BCl-2, c-Jun, c-Fos and Raf-1 proteins in the human cord blood cells after direct exposure to styrene, whereas p53 expression did not change. Furthermore, Macroarray analysis showed that styrene changed cord blood gene expression, inducing up-regulation of monocyte chemotactic protein 1 (MCP-1), and down-regulation of CC chemokine receptor type 1 (CCR-1) and SLP-76 tyrosine-phosphoprotein.
Diodovich
Cristina
C
Laboratory of Hematotoxicology, ECVAM Institute for Health and Consumer Protection, JRC, Ispra, Italy. cristina.diodovich@jrc.it
Bianchi
Marco Giorgio
MG
Bowe
Gerard
G
Acquati
Francesco
F
Taramelli
Roberto
R
Parent-Massin
Dominique
D
Gribaldo
Laura
L
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D017931:DNA Primers; D004345:Drug Industry; D004797:Enzyme-Linked Immunosorbent Assay; D015672:Erythroid Precursor Cells; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects*; D005818:Genetic Engineering; D006801:Humans; D066298:In Vitro Techniques; D009336:Necrosis; D020411:Oligonucleotide Array Sequence Analysis; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020058:Styrene / Q000633:toxicity*
D017931:DNA Primers; D020058:Styrene; D012313:RNA