Pyrimidine dimer removal enhanced by DNA repair liposomes reduces the incidence of UV skin cancer in mice.
UV exposure has been linked to skin cancer in humans by epidemiology and the rare genetic disease xeroderma pigmentosum. However, UV produces multiple photoproducts in DNA, and their relative contribution is uncertain. An enzyme which specifically repairs cyclobutane pyrimidine dimers in DNA, T4 endonuclease V, was encapsulated in liposomes for topical delivery into mouse and human skin. In both species, liposomes applied after UV exposure localized in the epidermis and stimulated the removal of cyclobutane pyrimidine dimers. UV-irradiated mice treated with these liposomes had a dose-dependent decrease in the incidence of squamous cell carcinoma compared to controls. The results demonstrate that unrepaired cyclobutane pyrimidine dimers in DNA are a direct cause of cancer in mammalian skin.
Yarosh
D
D
Applied Genetics Inc., Freeport, New York 11520.
Alas
L G
LG
Yee
V
V
Oberyszyn
A
A
Kibitel
J T
JT
Mitchell
D
D
Rosenstein
R
R
Spinowitz
A
A
Citron
M
M
D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004337:Drug Carriers; D004706:Endodeoxyribonucleases / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008081:Liposomes; D051379:Mice; D008812:Mice, Hairless; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000517:prevention & control*; D009924:Organ Culture Techniques; D011740:Pyrimidine Dimers / Q000032:analysis; D012867:Skin / Q000473:pathology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000209:etiology / Q000517:prevention & control*; D013604:T-Phages / Q000201:enzymology; D014018:Tissue Distribution; D014466:Ultraviolet Rays; D014764:Viral Proteins
D004337:Drug Carriers; D008081:Liposomes; D011740:Pyrimidine Dimers; D014764:Viral Proteins; D004706:Endodeoxyribonucleases; C470698:endonuclease V, phage T4; D043224:Deoxyribonuclease (Pyrimidine Dimer)