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

Ultraviolet-B (UVB) (290-320 nm) radiation-induced cyclobutane pyrimidine d imers 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 exclu sively 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-re pair enzyme photolyase, derived from Anacystis nidulans, that specifically converts cyclobutane dimers into their original DNA structure after exposur e to photoreactivating light. When a dose of UVB radiation sufficient to in duce 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 ex posure to photoreactivating light decreased the number of UVB radiation-ind uced dimers by 40-45%. No reduction was observed if the liposomes were not filled with photolyase or if photoreactivating exposure preceded the applic ation of filled liposomes, The UVB dose administered resulted in suppressio n of intercellular adhesion molecule-1 (ICAM-1), a molecule required for im munity and inflammatory events in the epidermis, In addition, in subjects h ypersensitive to nickel sulfate, elicitation of the hypersensitivity reacti on 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 t hat topical application of photolyase is effective in dimer reversal and th ereby leads to immunoprotection.