Enzyme plus light therapy to repair DNA damage in ultraviolet-B-irradiated human skin

Abstract

Ultraviolet-B (UVB) (290 -320 nm) radiation-induced cyclobutane pyrimidine dimers within the DNA of epidermal cells are detrimental to human health by causing mutations and immunosuppressive effects that presumably contribute to photocarcinogenesis. Conventional photoprotection by sunscreens is exclusively prophylactic in nature and of no value once DNA damage has occurred. In this paper, we have therefore assessed whether it is possible to repair UVB radiationinduced DNA damage through topical application of the DNA-repair enzyme photolyase, derived from Anacystis nidulans, that specifically converts cyclobutane dimers into their original DNA structure after exposure to photoreactivating light. When a dose of UVB radiation sufficient to induce erythema was administered to the skin of healthy subjects, significant numbers of dimers were formed within epidermal cells. Topical application of photolyase-containing liposomes to UVB-irradiated skin and subsequent exposure to photoreactivating light decreased the number of UVB radiation-induced dimers by 40 -45%. No reduction was observed if the liposomes were not filled with photolyase or if photoreactivating exposure preceded the application of filled liposomes. The UVB dose administered resulted in suppression of intercellular adhesion molecule-1 (ICAM-1), a molecule required for immunity and inflammatory events in the epidermis. In addition, in subjects hypersensitive to nickel sulfate, elicitation of the hypersensitivity reaction in irradiated skin areas was prevented. Photolyase-induced dimer repair completely prevented these UVB radiation-induced immunosuppressive effects as well as erythema and sunburn-cell formation. These studies demonstrate that topical application of photolyase is effective in dimer reversal and thereby leads to immunoprotection.

DNA damage, death receptor activation and reactive oxygen species contribute to ultraviolet radiation-induced apoptosis in an essential and independent way

“…Accordingly, patients suffering from xeroderma pigmentosum, a disease which is based on genetic defects in various components of the nucletoide excision repair (Kraemer et al, 1994) reveal an increased number of sunburn cells following UVB exposure (Petit-Frere et al, 2000). The crucial role of DNA damage in UVB-induced apoptosis has been further confirmed by in vivo studies showing that enhancement of DNA repair by the topical application of repair enzymes in liposomes reduces sunburn cell formation (Stege et al, 2000;Wolf et al, 1995). In addition, detection of sunburn cells in skin treated with other DNA damaging irradiation procedures (e.g.…”

IL-18 Reduces Ultraviolet Radiation-Induced DNA Damage and Thereby Affects Photoimmunosuppression

“…This demonstration was the first to show that a cytokine may modulate NER. Because induction of NER results in reduction of DNA damage it was suggested that modulation of the NER by a cytokine might represent a new strategy to prevent formation of skin cancer and could supplement other strategies, e.g., the application of exogenous DNA repair enzymes (13,14,37).…”

The dark side of the light: Phototherapy adverse effects

“…Photolyase, derived from a photosynthetic plant, has been proven effective in reverting DNA photoproducts (CPDs and 6-4 photoproducts) after UVB irradiation when given in exogenous preparations. 58 3. Exogenous oxoguanine DNA glycosylase-1 (OGG1), the enzyme recognizing and initiating the repair of UV-induced DNA oxidative damage (8-oxoG), has produced reductions in skin tumor size and malignant transformation rates in UV-irradiated mice.…”