Treatment of human melanocytes and S91 melanoma cells with the DNA repair enzyme T4 endonuclease V enhances melanogenesis after ultraviolet irradiation.
Tanning is a protective response of ultraviolet (UV)-irradiated skin that decreases damage from subsequent sun exposures by increasing the epidermal content of melanin, a brown-black pigment that absorbs light energy throughout the UV and visible portions of the electromagnetic spectrum. The melanin pigment is made by epidermal melanocytes and transferred to surrounding keratinocytes. The action spectrum, time course, and histologic features of tanning are well studied, but the initiating molecular events are unknown. Previous work has shown that T4 endonuclease V, a prokaryotic DNA repair enzyme that catalyzes the first and rate-limiting step in repair of UV-induced pyrimidine dimers, delivered in carrier liposomes (T4N5), enhances repair of UV-induced DNA damage in cultured human cells and protects against photocarcinogenesis in an animal model. We now report that T4N5 treatment enhances UV-induced melanogenesis, as measured by melanin content, tyrosinase activity, 14C-dopa incorporation, and visual assessment in both S91 murine melanoma cells and human melanocytes. T4N5 treatment also increases cell yields following UV irradiation. These data suggest that tanning can be stimulated through enhanced DNA repair.
Gilchrest
B A
BA
Department of Dermatology, Boston University School of Medicine, Ma. 02118.
Zhai
S
S
Eller
M S
MS
Yarosh
D B
DB
Yaar
M
M
D002455:Cell Division / Q000528:radiation effects; D002478:Cells, Cultured; D004260:DNA Repair; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D006801:Humans; D008543:Melanins / Q000032:analysis / Q000096:biosynthesis*; D008544:Melanocytes / Q000378:metabolism* / Q000528:radiation effects; D008546:Melanoma, Experimental / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D014764:Viral Proteins
D008543:Melanins; D014764:Viral Proteins; D004295:Dihydroxyphenylalanine; D004706:Endodeoxyribonucleases; C470698:endonuclease V, phage T4; D043224:Deoxyribonuclease (Pyrimidine Dimer)