Induction of cancer, actinic keratosis, and specific p53 mutations by UVB light in human skin maintained in severe combined immunodeficient mice
Nomura, T.; Nakajima, H.; Hongyo, T.; Taniguchi, E.; Fukuda, K.; Li, L.Y.; Kurooka, M.; Sutoh, K.; Hande, P.M.; Kawaguchi, T.; Ueda, M.; Takatera, H.
Cancer Research 57(11): 2081-2084
1997
ISSN/ISBN: 0008-5472 PMID: 9187098 Document Number: 482550
To study the mechanism and risk of human skin cancer from solar light, we exposed human skin transplanted to severe combined immunodeficient mice to daily doses of UVB for periods of approximately 2 years. We have succeeded for the first time in inducing cancer and solar (actinic) keratosis in human skin by UVB. Of 18 normal skins exposed to doses of 7.3 times 10-5 to 1.8 times 10-6 J/m-2, 14 actinic keratoses (77.8%) and 3 squamous cell carcinomas (16.7%) developed, whereas neither actinic keratosis nor cancer was observed in 15 human skins not exposed to UVB. Each human skin showed a different susceptibility, and skins sensitive for actinic keratosis were also sensitive for cancer induction. Among p53 mutations at various sites, mutation at codon 7.42 (C TGC fwdarw C CGC; Cys fwdarw Arg) was specifically observed in both skin cancers and actinic keratoses. Furthermore, double or triple mutations were induced in an UVB-induced skin cancers and in three of eight actinic keratoses. Most of the mutations (17 of 20) occurred at dipyrimidine sites.