Substrate specificity of the mouse skin mixedfunction oxidase system

Abstract

The metabolism of nine model substrates for the mixed-function oxidase system was studied in skin and liver microsomes from Balb/C mice. Rates of skin metabolism per mg microsomal protein ranged from 0.5-15% of liver rates depending on the substrate. Relative to liver, mouse skin preferentially metabolized ethoxyresorufin, benzo[alpha]pyrene and diphenyloxazole over aldrin, coumarin and the C1-C4 7-alkyl umbelliferone ethers. NADPH-cytochrome P-450-dependent metabolism of aldrin and ethoxyresorufin was differentially inhibited in skin microsomes by metyrapone and alpha-naphthoflavone, respectively. Biphasic Eadie-Hofstee plots were obtained in both skin and liver microsomes for the metabolism of aldrin, whereas metabolism of ethoxyresorufin in both systems was described by linear kinetics. It is concluded that mouse skin contains multiple forms of cytochrome P-450, and that forms functionally analogous to those induced by polycyclic hydrocarbons in rodent liver are present in untreated mouse skin.