Ultraviolet-B exposure of human skin induces cytochromes P450 1A1 and 1B1.
The cytochromes P450 belong to a multigene superfamily and are responsible for the metabolic activation of both xenobiotics and endobiotics. The expression of cytochrome P450 genes in target cells is an important determinant of human susceptibility to cancers and other chemically initiated diseases. In this study using immunohistochemistry, reverse transcription polymerase chain reaction, and western blot analysis, we investigated the cellular distribution and localization of cytochrome P450 1A1 and cytochrome P450 1B1 in human skin, and their induction by ultraviolet-B. Through the use of immunohistochemistry, cytochrome P450 1A1 was found to be primarily localized in the basal cell layer of the epidermis in non-ultraviolet-B exposed skin, whereas cytochrome P450 1B1 was localized in the epidermal cells other than the basal cell layer. Thus, localizations of cytochrome P450 1A1 and cytochrome P450 1B1 in human skin are different and may be related to keratinocyte differentiation. Ultraviolet-B exposure to solar-ultraviolet-protected skin (buttock site) resulted in an ultraviolet-B dose-dependent (0-4 minimal erythema doses) and time-dependent (0-48 h) induction of both cytochrome P450 1A1 and cytochrome P450 1B1 in the epidermis. Reverse transcription polymerase chain reaction and western blot analyses revealed that exposure of human skin to ultraviolet-B (4 minimal erythema doses) resulted in enhanced expression of mRNA and protein of both cytochrome P450 1A1 and cytochrome P450 1B1 in the epidermis. Ultraviolet-B induction of both cytochrome P450 1A1 and cytochrome P450 1B1 in human skin will probably result in enhanced bioactivation of polycyclic aromatic hydrocarbons and other environmental pollutants to which humans are exposed, which in turn could make the human skin more susceptible to ultraviolet-B-induced skin cancers or allergic and irritant contact dermatitis.
Katiyar
S K
SK
Department of Dermatology, Case Western Reserve University, and University Hospitals of Cleveland, Cleveland, OH 44106, USA.
Matsui
M S
MS
Mukhtar
H
H
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004307:Dose-Response Relationship, Radiation; D004790:Enzyme Induction / Q000528:radiation effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000201:enzymology* / Q000528:radiation effects*; D014018:Tissue Distribution; D014466:Ultraviolet Rays
D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1