In vivo metabolism of topically applied benzo[a]pyrene-4,5-oxide in neonatal rat skin.
The metabolism of benzo[a]pyrene (BP)-4,5-oxide in the skin and liver of neonatal rats was studied after topical application of the arene oxide in vivo. The metabolism of BP-4,5-oxide was time-dependent and showed a 2-h maximum for BP-4,5-dihydrodiol formation in both skin and liver. Product formation was also dose-dependent. Inhibitors of epoxide hydrolase such as clotrimazole, 1,1,1,-trichloropropene oxide, and cyclohexene oxide largely abolished the formation of BP-4,5-dihydrodiol. The rapid biotransformation of arene oxides such as BP-4,5-oxide in the skin emphasizes the potential importance of epoxide hydrolase in the activation and inactivation of polycyclic aromatic hydrocarbons. Furthermore, the topically applied arene oxide also penetrated the skin and was rapidly metabolized in the liver as well.
D000287:Administration, Topical; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001580:Benzopyrenes / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000378:metabolism*; D013997:Time Factors
D001580:Benzopyrenes; C006707:benzo(a)pyrene 4,5-epoxide; D004851:Epoxide Hydrolases