Increase of CYP1B1 transcription in human keratinocytes and HaCaT cells after UV-B exposure

Toxicol Appl Pharmacol. 2002 Feb 1;178(3):137-43. doi: 10.1006/taap.2001.9335.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amanitins / pharmacology
  • Aryl Hydrocarbon Hydroxylases*
  • Benzoflavones / pharmacology
  • Cells, Cultured
  • Cytochrome P-450 CYP1B1
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Enzyme Induction / drug effects
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism*
  • Keratinocytes / radiation effects
  • Receptors, Aryl Hydrocarbon / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / genetics*
  • Transcriptional Activation / radiation effects
  • Ultraviolet Rays*


  • Amanitins
  • Benzoflavones
  • Enzyme Inhibitors
  • Receptors, Aryl Hydrocarbon
  • alpha-naphthoflavone
  • Cytochrome P-450 Enzyme System
  • Aryl Hydrocarbon Hydroxylases
  • CYP1B1 protein, human
  • Cytochrome P-450 CYP1B1