EVIDENCE FOR MULTIPLE INDUCIBLE CYTOCHROME-P450 ISOZYMES IN SENCAR MOUSE SKIN BY PYRIDINE

Pyridine, an amphipathic solvent, is widely used in industry and is al so a constituent of tobacco and its smoke. Since, in addition to inhal ation and ingestion, pyridine is also readily absorbed through skin, w e assessed the effect of skin application of pyridine on monooxygenase activities and cytochrome P450 (CYP) isozymes and CYP mRNA levels in the skin of SENCAR mice. Compared to controls, a single topical applic ation of pyridine (30 or 50 mg/100 g body weight) resulted in inductio n of cutaneous 7-ethoxyresorufin O-deethylase, 7-pentoxyresorufin O-de pentylase, and erythromycin N-demethylase activities. Pyridine treatme nt also resulted in an increase in reactivity with monoclonal antibodi es directed against CYP 1A1, 2B1 and 3A. In Northern blot analysis, tr eatment of pyridine also showed a significant increase in mRNA for Cyp 1a-1 in the skin. These data indicate that murine skin contains multip le inducible CYP isozymes, and that pyridine results in the induction of at least three families of CYP in murine skin. (C) Academic Press, Inc.