DISTRIBUTION OF XENOBIOTIC-METABOLIZING ENZYMES IN SKIN

In the present study, the distribution and nature of specific xenobiotic-metabolizing enzymes has been studied. Immunocytochemistry revealed the specific isoenzyme profile of the different cell types in mouse, rat and human skin. Constitutive levels of cytochrome P-450 1A1/A2 (CYP1A1/A2), CYP2B1/B2 and glutathione S-transferase were concentrated in the epidermis and sebaceous glands of all three species. Enzymic digestion followed by density gradient centrifugation resulted in fractions enriched in sebaceous cells, basal cells and differentiated keratinocytes. The basal and sebaceous cells of mouse skin were found to contain high levels of CYP1A1/A2, which was induced approximately 10-fold following beta-naphthoflavone pretreatment. These findings suggest that xenobiotic metabolizing enzymes exhibit a similar qualitative distribution between the cell types of rodent and human skin and that these cell types may be isolated for use in mechanistic studies involving cutaneous metabolism and toxicity.