Ultraviolet-B Exposure of Human Skin Induces Cytochromes P450 1A1 and 1B1

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.

The cancer preventative agent resveratrol is converted to the anticancer agent piceatannol by the cytochrome P450 enzyme CYP1B1

“…Indeed tumour cells exposed to activated carcinogens may well die from the mutagenic damage, resulting in a cytotoxic effect (Shen et al, 1994). With respect to our hypothesis another relevant observation is that CYP1B1 is induced in skin cells on exposure to mutagenic UV light (Katiyar et al, 2000). Our hypothesis may also explain the cancer preventative properties of other phytoestrogens (Adlercreutz, 1995) such as flavones, especially as it has recently been found that some flavonoids are substrates for CYP1B1 (Doostdar et al, 2000).…”

Lightening up the UV response by identification of the arylhydrocarbon receptor as a cytoplasmatic target for ultraviolet B radiation

“…Prompted by the observations that UVB irradiation induces CYP not only in the skin, but also in extracutaneous organs in vivo (24,25,46,47), the intracellular generation of CYP-inducing photoproducts was proposed. Indeed, tryptophan products which were generated by irradiating an aqueous solution of tryptophan with a UVB source were found to be strong AhR ligands (32).…”

“…We have hypothesized that AhR signaling is part of the UVB response, because not only known AhR ligands, but also exposure of rat and human skin to UVB induces AhR-dependent CYP1A activity and CYP1A1/1B1 mRNA and protein expression, respectively (24,25). Also, transcriptional expression of CYP1A1 can be induced by UVB radiation in human cells in vitro (26).…”

Ultraviolet Light Induced Alteration to the Skin

“…They also play an important part in the protective role of the skin. The expression of CYP genes in target cells seems to be an important determinant in the human susceptibility to cancers including skin cancers 46,47 . CYP1A1, widely expressed in extrahepatic tissues, is up-regulated in response to UV.…”