Induction of CYP1A1 by serum independent of AhR pathway.
CYP1A1 is implicated in the bioactivation of procarcinogens such as polycyclic aromatic hydrocarbons. To date, no physiological compounds have been described as inducers of this gene. In this study, we have examined the role of serum in the regulation of CYP1A1 gene expression. After treatment of CaCo-2 cells with fetal bovine serum, CYP1A1 mRNA level increased to the same extent as that observed after 3-methylcholanthrene induction. The same effect was obtained after treatment with adult bovine or human serum. Evaluation of hnRNA level performed on CaCo-2 cells indicates that CYP1A1 induction by serum acts at least in part through transcriptional activation. Promoter region containing the XRE (1.56 kb) was tested in the CAT assay. No stimulation of this reporter gene was detected after serum treatment. These results demonstrate for the first time that physiological compound(s) contained in serum induces CYP1A1 gene expression by transcriptional activation independent of the AhR pathway.
Guigal
N
N
Faculté de Pharmacie, UPRES A CNRS 6032, 27 boulevard Jean Moulin, Marseille Cedex 05, 13385, France.
Seree
E
E
Bourgarel-Rey
V
V
Barra
Y
Y
D000328:Adult; D000818:Animals; D001483:Base Sequence; D018938:Caco-2 Cells; D002417:Cattle; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003470:Culture Media; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D008748:Methylcholanthrene / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects
D003470:Culture Media; D017931:DNA Primers; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D008748:Methylcholanthrene; D019363:Cytochrome P-450 CYP1A1; D015500:Chloramphenicol O-Acetyltransferase