| First Author | Yamazaki F | Year | 2004 |
| Journal | J Invest Dermatol | Volume | 123 |
| Issue | 1 | Pages | 220-8 |
| PubMed ID | 15191564 | Mgi Jnum | J:90498 |
| Mgi Id | MGI:3044020 | Doi | 10.1111/j.0022-202X.2004.22710.x |
| Citation | Yamazaki F, et al. (2004) XPA Gene-Deficient, SCF-Transgenic Mice with Epidermal Melanin Are Resistant to UV-Induced Carcinogenesis. J Invest Dermatol 123(1):220-8 |
| abstractText | Photobiologic investigations have been performed using animals without epidermal melanocytes. We developed xeroderma pigmentosum group A gene-deficient (XPA (-/-)), stem cell factor transgenic (SCF-Tg) mice, which one defective in nucleotide excision repair and have epidermal melanocytes, and investigated protective effects of epidermal melanin against UV-induced injuries. When irradiated to UVB, XPA (-/-) mice developed greatly enhanced responses including acute inflammation, cyclobutane pyrimidine dimer (CPD) formation, keratinocyte apoptosis, depletion of Langerhans cells and immunosuppression of contact hypersensitivity, but XPA (-/-), SCF-Tg mice showed much less responses to the same dose of UVB. XPA (-/-), SCF-Tg mice did not develop skin cancers after repeated exposures to UVB for 30 wk at a total dose of 72 J per cm(2), which induced a significant number of tumors even in wild-type, XPA (+/+) mice, and was lethal dose for XPA (-/-) mice. Dimethylbenz (alpha) anthracence (DMBA) induces DNA damages, which require XPA protein to be repaired. Topical application of DMBA produced a significant inflammation, CPD formation, apoptosis, immunosuppression, and skin cancers in XPA (-/-), SCF-Tg mice as well as XPA (-/-) mice. These findings indicate that epidermal melanin has a high ability to protect DNA damage by UVB radiation, and thereby, prevent UV-induced inflammation, immunosuppression, and carcinogenesis. |
