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The expression, in adult human skin, of genes encoding flavin-containing monooxygenases (FMOs) 1, 3, 4, and 5 and cytochromes P450 (CYPs) 2A6, 2B6, and 3A4 was determined by RNase protection. Each FMO and CYP exhibits inter-individual variation in expression in this organ. Of the individuals analysed, all contained CYP2B6 mRNA in their skin, 90% contained FMO5 mRNA and about half contained mRNAs encoding FMOs 1, 3, and 4, and CYPs 2A6 and 3A4. The amount of each of the FMO and CYP mRNAs in skin is much lower than in the organ in which it is most highly expressed, namely the kidney (for FMO1) and the liver (for the others). In contrast to the latter organs, in the skin FMO mRNAs are present in amounts similar to, or greater than, CYP mRNAs. Only the mRNA encoding CYP2B6 decreased in abundance in skin with increasing age of the individual. All of the mRNAs were substantially less abundant in cultures of keratinocytes than in samples of skin from which the cells were derived. In contrast, an immortalized human keratinocyte cell line, HaCaT, expressed FMO3, FMO5, and CYP2B6 mRNAs in amounts that fall within the range detected in the whole skin samples analysed. FMO1, CYP2A6, and CYP3A4 mRNAs were not detected in HaCaT cells, whereas FMO4 expression was markedly increased in this cell line compared to whole skin. In situhybridization showed that the expression of each of the FMOs and CYPs analysed was localized to the epidermis, sebaceous glands and hair follicles.