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 expre ssion 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 di stribution and localization of cytochrome P450 1A1 and cytochrome P450 1B1 in human skin, and their induction by ultraviolet-B. Through the use of imm unohistochemistry, 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 tha n the basal cell layer. Thus, localizations of cytochrome P450 1A1 and cyto chrome P450 1B1 in human skin are different and may be related to keratinoc yte differentiation. Ultraviolet-B exposure to solar-ultraviolet-protected skin (buttock site) resulted in an ultraviolet-B dose-dependent (0-4 minima l erythema doses) and time-dependent (0-48 h) induction of both cytochrome P450 1A1 and cytochrome P450 1B1 in the epidermis. Reverse transcription po lymerase chain reaction and western blot analyses revealed that exposure of human skin to ultraviolet-B (4 minimal erythema doses) resulted in enhance d expression of mRNA and protein of both cytochrome P450 1A1 and cytochrome P450 1B1. in the epidermis, Ultraviolet-B induction of both cytochrome P45 0 1A1 and cytochrome P450 1B1 in human skin will probably result in enhance d 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 an d irritant contact dermatitis.