Photoprotection by topical DNA repair enzymes: molecular correlates of clinical studies.
A new approach to photoprotection is to repair DNA damage after UV exposure. This can be accomplished by delivery of a DNA repair enzyme with specificity to UV-induced cyclobutane pyrimidine dimers into skin by means of specially engineered liposomes. Treatment of DNA-repair-deficient xeroderma pigmentosum patients or skin cancer patients with T4N5 liposome lotion containing such DNA repair liposomes increases the removal of DNA damage in the first few hours after treatment. In these studies, a DNA repair effect was observed in some patients treated with heat-inactivated enzyme. Unexpectedly, it was discovered that the heat-inactivated T4 endonuclease V enzyme refolds and recovers enzymatic activity. These studies demonstrate that measurements of molecular changes induced by biological drugs are useful adjuvants to clinical studies.
Yarosh
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AGI Dermatics, Freeport, NY 11420, USA. agiderm@aol.com
O'Connor
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Alas
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Potten
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Wolf
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D000287:Administration, Topical; D000818:Animals; D004260:DNA Repair; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004337:Drug Carriers; D004706:Endodeoxyribonucleases / Q000008:administration & dosage / Q000627:therapeutic use*; D008081:Liposomes; D009824:Ointments; D017510:Protein Folding; D012867:Skin / Q000187:drug effects / Q000528:radiation effects; D012878:Skin Neoplasms / Q000188:drug therapy*; D014466:Ultraviolet Rays; D014764:Viral Proteins; D014983:Xeroderma Pigmentosum / Q000188:drug therapy*
D004337:Drug Carriers; D008081:Liposomes; D009824:Ointments; D014764:Viral Proteins; D004706:Endodeoxyribonucleases; C470698:endonuclease V, phage T4; D043224:Deoxyribonuclease (Pyrimidine Dimer)