Drug metabolism in skin. Comparative activity of the mixed-function oxidases, epoxide hydratase, and glutathione S-transferase in liver and skin of the neonatal rat.

Aryl hydrocarbon hydroxylase (AHH) activity in the skin of neonatal rats was compared to that in epidermis, dermis, and other body tissues. Following topical application of benzo[a]pyrene (BP) or the polychlorinated biphenyl mixture Aroclor 1254 there was induction of AHH in each tissue studied. There was a greater increase in the activity of skin enzyme as compared to other extrahepatic tissues. When whole-organ activity (pmol of 3-OH-BP per min per whole organ) was considered, skin represented 2%, 21%, and 27% or whole body activity in control, BP-treated, and Aroclor 1254-treated animals, respectively. Skin microsomes from control rats exhibited 2, 0.5, 24, and 6% of corresponding liver microsomal AHH, 7-ethoxycoumarin de-ethylase, NADPH-cytochrome c reductase, and epoxide hydratase activities, respectively. Glutathione S-transferase activity in skin cytosol was 15% of the corresponding hepatic activity. Following topical application of Aroclor 1254 there were increases in the activity of AHH and 7-ethoxycoumarin de-ethylase in the skin and the liver. Glutathione S-transferase (40-60%) and epoxide hydratase (83-94%) activities in neonatal rat liver were induced by skin application of Aroclor 1254.