Induction of CYP1A1 mRNA in rat epidermis and cultured human epidermal keratinocytes by benz(a)anthracene and beta-naphthoflavone.
Cytochrome P-4501A1 (CYP1A1) plays a major role in the bioactivation of procarcinogens in target tissues, including skin. However, the factors controlling CYP1A1 expression in mammalian skin are unknown. Utilizing the reverse transcriptase-linked polymerase chain reaction, we analyzed the effect of treatment with beta-naphthoflavone (beta-NF) and benz(a)anthracene on the expression of CYP1A1 mRNA in rat epidermis and normal human epidermal keratinocytes (NHEK). Inducer treatment of rats and NHEKs resulted in several-fold increases in aryl hydrocarbon hydroxylase activity. Following inducer treatment of adult or neonatal rats, increase in CYP1A1 gene message occurred as compared with that in controls. Higher basal level and inducibility were detected in mature rather than in 4-day-old rats. This induction occurred as early as 4 hr after beta-NF application. Exposure to beta-NF and benz(a)anthracene also resulted in substantial increases in gene message in NHEK. Northern blot analyses complemented the polymerase chain reaction data. These results indicate that CYP1A1 gene expression is increased in mammalian epidermis by inducers of epidermal aryl hydrocarbon hydroxylase activity.
Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University, OH.
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Khan
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Bickers
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Haqqi
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Mukhtar
D000818:Animals; D001483:Base Sequence; D001551:Benz(a)Anthracenes / Q000494:pharmacology*; D001571:Benzoflavones / Q000494:pharmacology*; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D015603:Keratinocytes / Q000378:metabolism*; D008969:Molecular Sequence Data; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019324:beta-Naphthoflavone
D001551:Benz(a)Anthracenes; D001571:Benzoflavones; D012333:RNA, Messenger; D019324:beta-Naphthoflavone; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; C030935:benz(a)anthracene