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

摘要

Ultraviolet-B (UVB) (290--320 nm) radiation-induced cyclobutane py- rimidine dimers within the DNA Of epidermal cells are detrimental to human health by causing mutations and immunosuppressive effects that presumably contribute to photocarcinogenesis. Conventional photoprotedion 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 radiation- induced DNA damage through topical application of the DNA-repair enzyme photolyase. derived from Anaoptis nbolans. that specifically converts Cyclobutene 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 epider- mal 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 ap- plication of filled liposomes. The UVB dose administered resulted in suppression of intercellular adhesion molecuIe-1 (lCAM-1). a molecule required for immunity and inflammatory events in the epidermis. In addition, in subject 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.