Presence of a retinoid responsive element in the promoter region of the human cytochrome P4501A1 gene.

Cytochrome P4501A1 (CYP1A1) plays a key role in the metabolic activation of procarcinogenic compounds, leading to skin carcinogenesis. It is therefore important to determine whether its enzymatic activity is altered by topically administered drugs. We investigated, in cultured normal human keratinocytes (NHK), the effects of retinoic acid (RA) and synthetic analogs on the regulation of the CYP1A1 gene. Using transient transfections and gel shift assays, we demonstrated that the human CYP1A1 gene promoter was differentially regulated by retinoid receptors. We report, for the first time, that a RA responsive element 5'-CTTAGGTCACCACGGGGCA-3' (RARE1A1) is present within the promoter region of the CYP1A1 gene.