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Background: Ultraviolet (UV) radiation damages the cellular DNA of skin cells. In response, wild-type p53 protein accumulates in irradiated cells and the stabilized and transactivated protein can then induce genes involved in cell cycle arrest in G1, or in the initiation of apoptosis. Selenium protects cells from UVB-induced cell death and apoptosis by mechanisms which are unclear, although recent reports suggest that selenium protects against UV-induced cell damage by inducing DNA repair enzymes and transactivating p53. Methods: We examined whether selenomethionine could protect human skin cells from UV radiation-induced p53 transactivation, using a pRGCΔ fos-lacZ p53-dependent reporter construct stably transfected in an amelanotic melanoma cell line (Arn-8) which expresses wild-type p53. Cells were pretreated with or without selenomethionine and then irradiated with broadband UVB (∼270–350 nm); 0–30 mJ/cm2 from a Phillips TL100 W/12 lamp. Results: The percentage of cells with transcriptionally active p53 increased dose dependently up to 20 mJ/cm2 UVB. Treatment with 50 μM selenomethionine for 24 h both pre- and post-irradiation, significantly diminished p53 activation by 30–43% across the UV dose range ( P=0.0085, n=5 independent experiments) and decreased UV-induced p53 protein accumulation as assessed by Western blotting. Conclusions: We conclude that selenomethionine inhibits broad band UVB-induced p53 transactivation and protein accumulation and that this effect correlates with reported protective effects of selenium against UV-induced DNA damage. [ABSTRACT FROM AUTHOR]

Leukemia inhibitory factor (LIF) is a polyfunctional cytokine with a variety and a diverse range of biological activities. However, this is a reflection of the fact that the cytokine is expressed in many different tissues, has a wide target cell range, and fulfills different functions in different tissues. The purpose of this article is to examine what is known about LIF expression in the skin and to consider whether LIF plays a role in inflammatory and hyperplastic events in the skin. LIF is strongly expressed in skin tumors, and recent studies indicate that it may affect tumor growth by several different mechanisms. The biological activities of LIF relevant to carcinogenesis, its expression, and signal transduction by the LIF receptor are described. Expression of LIF in normal skin by skin tumors and its induction by ultraviolet radiation and proinflammatory stimuli are discussed, as are possible interactions between LIF, mast cells, and tumor growth. We consider what role LIF and other members of the hemopoietin family of cytokines play in healthy and diseased skin and whether LIF could play a role in hyperplastic skin disorders. LIF appears to be an important cytokine for normal keratinocyte growth and wound healing and may be involved in regulating the proliferation of skin tumors. Accordingly, LIF may be a useful target for anticancer therapy and as a growth factor for normal skin during reconstructive surgery. R. C. MCKENZIE, MBA, PHD, AND J. SZEPIETOWSKI, MD, PHD HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS. [ABSTRACT FROM AUTHOR]

Selenium (Se) has protective properties against ultraviolet (UV)-induced changes in skin cells in vitro but little is known about such activity in human subjects. In the present study, seven patients with psoriasis ingested 400 μg of sodium selenite daily during a 4 week course of whole-body narrow-band UVB (TL01) therapy while six more psoriasis patients, similarly irradiated, ingested a placebo. Skin biopsies, collected at the start and end of the phototherapy were analysed for phosphorylated p53, Fas, Bcl-2, Bax and oxidized guaninosine, and for numbers of Langerhans and sunburn cells. Following the TL01 therapy, no significant difference was observed for any of these markers when the Se group was compared with the placebo group of patients, although p53 and Bcl-2 expression decreased in the Se supplemented group. [ABSTRACT FROM AUTHOR]

Recent studies published in Oncogene and Proc. Natl. Acad. Sci. USA ascribe a role for selenium, acting through wild type p53, in protecting skin cells in culture from ultraviolet radiation-induced death. While selenium clearly protects cells against ultraviolet radiation-induced death, data that we present and discuss in this letter shows that wild type p53 is not required for such protection. Moreover the non-physiologically high levels of selenium used in some studies leads us to question the relevance of such effects for selenium-induced photoprotection. [Copyright &y& Elsevier]

The mechanisms whereby narrowband ultraviolet B (UVB) (311–313 nm, TL01) phototherapy are effective in psoriasis may differ from those occurring in broadband UVB phototherapy. In the present study, changes in epidermal cells as a result of TL01 therapy were assessed in the skin of patients with psoriasis. The non-lesional skin of five subjects with plaque psoriasis was biopsied before and after a series of 12 whole-body TL01 treatments. Following appropriate staining of skin sections, the numbers of p53-positive keratinocytes, sunburn cells and Langerhans cells in the epidermis were counted. TL01 therapy induced a threefold increase in the number of p53-positive epidermal cells, a 12-fold increase in sunburn cells and a twofold decrease in Langerhans cells. The increase in epidermal p53 expression and apoptosis of keratinocytes together with the depletion of Langerhans cells in the non-lesional skin of psoriasis patients are likely to contribute to the effectiveness of TL01 phototherapy. [ABSTRACT FROM AUTHOR]