DNA repair, immunosuppression, and skin cancer.
UV radiation (UVR) produces erythema within the first 24 hours of exposure, suppression of the immune system within the first 10 days, and, for many people, over the course of decades, skin cancer. Although UVR damages many skin targets, DNA damage in the form of cyclobutane pyrimidine dimers (CPDs) is an important mediator of these sequelae. The action spectrum for erythema parallels the action spectrum for CPD formation in skin, and in the absence of repair, as in the genetic disease xeroderma pigmentosum (XP), skin cancer rates are dramatically increased. DNA repair in skin can be enhanced by the delivery of DNA repair enzymes encapsulated in liposomes. Used in this way, photoreactivation of CPDs greatly diminishes erythema and the suppression of contact hypersensitivity (CHS). UV endonucleases delivered by liposomes also prevent UV-induced suppression of delayed-type hypersensitivity. In a clinical study of patients with XP, T4 endonuclease V (T4N5) liposome lotion applied for one year reduced the rates of actinic keratosis (AK) and skin cancer compared with placebo. These results showed that strategies to increase sun protection should include measures to reduce DNA damage and increase the rate of DNA repair.
Yarosh
Daniel B
DB
AGI Dermatics, Freeport, New York, USA.
D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000008:administration & dosage; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000008:administration & dosage; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics*; D008081:Liposomes; D011740:Pyrimidine Dimers / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics* / Q000517:prevention & control; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014764:Viral Proteins / Q000008:administration & dosage
D008081:Liposomes; D011740:Pyrimidine Dimers; D014764:Viral Proteins; C470698:endonuclease V, phage T4; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004255:Deoxyribodipyrimidine Photo-Lyase