Reduction of ultraviolet-induced skin cancer in mice by topical application of DNA excision repair enzymes.
Ultraviolet (UV) irradiation produces two major photoproducts, cyclobutane pyrimidine dimers (CPD) and (6-4) photoproducts. T4 endonuclease V (T4N5), which specifically repairs CPD, is encapsulated in liposomes. A previous study has shown that UV-induced carcinogenesis in mice was suppressed by the application of T4N5 liposomes. To confirm the suppressive effect, we applied T4N5 liposomes with repeated UVB exposure to hairless mice. At the end of the experiment, mice treated with T4N5 liposomes had 3.5 +/- 1.3 tumors per mouse, and control mice had 6.3 +/- 2.8 tumors per mouse. In addition, the incidence of tumors was reduced in T4N5 liposome-treated mice compared with controls. The pathological diagnosis of the tumors was not significantly different between two groups. Immunohistochemical analysis of p53 protein in UV-induced tumors showed that nearly half of the tumors in both groups were positive. When the biopsied normal-looking skin taken during the experiment was stained with p53 antibody, there was no significant difference of the timing of p53 protein expression between the control mice and T4N5 liposome-treated mice. These results confirmed that CPD plays a pivotal role in UV carcinogenesis, although the molecular mechanisms of the suppression by T4N5 liposomes should be further clarified.
Bito
T
T
Department of Dermatology, Kobe University School of Medicine, Japan.
Ueda
M
M
Nagano
T
T
Fujii
S
S
Ichihashi
M
M
D000287:Administration, Topical; D000818:Animals; D002278:Carcinoma in Situ / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D004260:DNA Repair; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004337:Drug Carriers; D004706:Endodeoxyribonucleases / Q000008:administration & dosage*; D005260:Female; D007150:Immunohistochemistry; D008081:Liposomes; D051379:Mice; D008812:Mice, Hairless; D009381:Neoplasms, Radiation-Induced / Q000517:prevention & control*; D010212:Papilloma / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D012878:Skin Neoplasms / Q000737:chemistry / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014764:Viral Proteins
D004337:Drug Carriers; D008081:Liposomes; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; D004706:Endodeoxyribonucleases; C470698:endonuclease V, phage T4; D043224:Deoxyribonuclease (Pyrimidine Dimer)