Quantification and cellular localization of expression in human skin of genes encoding flavin-containing monooxygenases and cytochromes P450

The expression, in adult human skin, of genes encoding flavin-containing mo nooxygenases (FMOs) 1, 3, 4, and 5 and cytochromes P450 (CYPs) 2A6, 2B6, an d 3A4 was determined by RNase protection. Each FMO and CYP exhibits inter-i ndividual variation in expression in this organ. Of the individuals analyse d, all contained CYP2B6 mRNA in their skin, 90% contained FMO5 mRNA and abo ut half contained mRNAs encoding FMOs 1, 3, and 4, and CYPs 2A6 and 3A4. Th e amount of each of the FNIO and CYP mRNAs in skin is much lower than in th e organ in which it is most highly expressed, namely the kidney (for FMO I) and the liver (for the others). In contrast to the latter organs, in the s kin FMO mRNAs are present in amounts similar to, or greater than, CYP mRNAs . Only the mRNA encoding CYP2B6 decreased in abundance in skin with increas ing age of the individual. All of the mRNAs were substantially less abundan t in cultures of keratinocytes than in samples of skin from which the cells were derived. In contrast, an immortalized human keratinocyte cell line, H aCaT, expressed FMO3, FMO5, and CYP2B6 mRNAs in amounts that fall within th e range detected in the whole skin samples analysed. FMO1, CYP2A6, and CYP3 A4 mRNAs were not detected in HaCaT cells, whereas FMO4 expression was mark edly increased in this cell line compared to whole skin. In situ hybridizat ion showed that the expression of each of the FMOs and CYPs analysed was lo calized to the epidermis, sebaceous glands and hair follicles. (C) 2001 Els evier Science Inc. All rights reserved.