Increase of CYP1B1 transcription in human keratinocytes and HaCaT cells after UV-B exposure.
Nonmelanoma skin cancers represent the most common malignant neoplasms in humans. UV-B play a major role in the etiology of these tumors, but exposure to environmental procarcinogens is also involved. CYP catalyzes numerous chemical carcinogen bioactivations and effects of UV-B on their expression are poorly understood. The aim of this study was to explore the molecular events involved in the induction of CYP1B1, a major cutaneous CYP, by UV-B. Our results demonstrated that unique UV-B exposure (20 mJ/cm(2)) increases human CYP1B1 transcript in primary keratinocytes and HaCaT cell cultures. Among 20 human samples studied, we observed a large interindividual variability of CYP1B1 mRNA induction (1.1- to 4.5-fold). Pretreatment with an antioxidant, N-acetylcysteine, repressed CYP1B1 increase, suggesting the involvement of UV-B photoproducts. alpha-Amanitin inhibition studies and CAT assays demonstrated that CYP1B1 mRNA induction is associated with a transcriptional activation of its expression. alpha-Naphthoflavone inhibition studies and CAT assays performed after directed mutagenesis of xenobiotic responsive element sites showed the involvement of Ah receptor. Taken together, these data demonstrated that UV-B induces CYP1B1 gene expression after an activation of its transcription, which involves Ah receptor.
Villard
Pierre H
PH
UMR-CNRS 6032, School of Pharmacy, University Méditérranée, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France.
Sampol
Emmanuelle
E
Elkaim
Jean L
JL
Puyoou
Franck
F
Casanova
Dominique
D
Sérée
Eric
E
Durand
Alain
A
Lacarelle
Bruno
B
D000546:Amanitins / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases; D001571:Benzoflavones / Q000494:pharmacology; D002478:Cells, Cultured; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D014466:Ultraviolet Rays
D000546:Amanitins; D001571:Benzoflavones; D004791:Enzyme Inhibitors; D018336:Receptors, Aryl Hydrocarbon; C011512:alpha-naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1