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Ultraviolet-B exposure of human skin induces cytochromes P450 1A1 and 1B1
S K Katiyar1, M S Matsui, H Mukhtar
1Department of Dermatology, Case Western Reserve University, and University Hospitals of Cleveland, Cleveland, OH 44106, USA.
Abstract:
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.
Insights
Cytochrome P450 1A1 and 1B1 are found in different skin layers. Ultraviolet-B radiation increases their levels, potentially increasing susceptibility to skin cancer and dermatitis.
Area of Science:
- Biochemistry
- Dermatology
- Molecular Biology
Background:
- Cytochromes P450 (CYP) are crucial for metabolizing xenobiotics and endobiotics.
- Gene expression of CYP enzymes influences susceptibility to chemically induced diseases, including cancers.
- Understanding CYP distribution and regulation in skin is vital for assessing environmental risk.
Purpose of the Study:
- To determine the cellular distribution and localization of CYP1A1 and CYP1B1 in human skin.
- To investigate the induction of CYP1A1 and CYP1B1 by ultraviolet-B (UVB) radiation.
- To assess the implications of CYP induction on skin's susceptibility to environmental pollutants and UV damage.
Main Methods:
- Immunohistochemistry was used to visualize protein localization in skin tissue.
- Reverse transcription polymerase chain reaction (RT-PCR) assessed mRNA expression levels.
- Western blot analysis quantified protein expression changes.
- UVB exposure was administered to solar-protected skin sites at varying doses and time points.
Main Results:
- CYP1A1 was primarily localized in the basal epidermal layer, while CYP1B1 was found in non-basal epidermal cells.
- UVB exposure induced both CYP1A1 and CYP1B1 in a dose- and time-dependent manner.
- RT-PCR and Western blot confirmed increased mRNA and protein expression of both CYPs in the epidermis after UVB exposure.
Conclusions:
- CYP1A1 and CYP1B1 exhibit distinct cellular localizations in human skin, possibly linked to keratinocyte differentiation.
- UVB induction of CYP1A1 and CYP1B1 enhances the bioactivation of environmental pollutants.
- This enhanced bioactivation may increase human skin's susceptibility to UVB-induced skin cancers and contact dermatitis.