Increase of CYP1B1 Transcription in Human Keratinocytes and HaCaT Cells after UV-B Exposure
Résumé
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 bio-activations 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.-Amanitin inhibition studies and CAT assays demonstrated that CYP1B1 mRNA induction is associated with a transcriptional activation of its expression.-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.
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