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 activati on of procarcinogenic compounds, leading to skin carcinogenesis. It is therefore important to determine whether its enzymatic activity is al tered by topically administered drugs. We investigated, in cultured no rmal human keratinocytes (NHK), the effects of retinoic acid (RA) and synthetic analogs on the regulation of the CYP1A1 gene. Using transien t transfections and gel shift assays, we demonstrated that the human C YP1A1 gene promoter was differentially regulated by retinoid receptors . We report, for the first time, that a RA responsive element 5'-CTTAG GTCACCACGGGGCA-3' (RARE1A1) is present within the promoter region of t he CYP1A1 gene. (C) 1994 Academic Press, Inc.