Evidence for multiple inducible cytochrome P450 isozymes in SENCAR mouse skin by pyridine.
Pyridine, an amphipathic solvent, is widely used in industry and is also a constituent of tobacco and its smoke. Since, in addition to inhalation and ingestion, pyridine is also readily absorbed through skin, we 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 application of pyridine (30 or 50 mg/100 g body weight) resulted in induction of cutaneous 7-ethoxyresorufin O-deethylase, 7-pentoxyresorufin O-depentylase, and erythromycin N-demethylase activities. Pyridine treatment also resulted in an increase in reactivity with monoclonal antibodies directed against CYP 1A1, 2B1 and 3A. In Northern blot analysis, treatment of pyridine also showed a significant increase in mRNA for Cyp1a-1 in the skin. These data indicate that murine skin contains multiple inducible CYP isozymes, and that pyridine results in the induction of at least three families of CYP in murine skin.
Agarwal
R
R
Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University, Ohio 44106.
Jugert
F K
FK
Khan
S G
SG
Bickers
D R
DR
Merk
H F
HF
Mukhtar
H
H
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000302:isolation & purification; D004790:Enzyme Induction; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology*; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010088:Oxidoreductases / Q000096:biosynthesis / Q000302:isolation & purification; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis / Q000302:isolation & purification; D011725:Pyridines / Q000633:toxicity*; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000302:isolation & purification; D012867:Skin / Q000187:drug effects / Q000201:enzymology*
D015345:Oligonucleotide Probes; D011725:Pyridines; D012333:RNA, Messenger; D012313:RNA; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; C023666:pyridine