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Induction of Cancer, Actinic Keratosis, and Specific p53 Mutations by UVB Light in Human Skin Maintained in Severe Combined Immunodeficient Mice¹

Departments of Radiation Biology [T. N., H. N., T. H., E. T., K. F., L. Y. L., M. K., K. S., P. M. H., T. K., H. T.], Surgery 1 [E. T., T. K.], and Otorhinolaryngology [K. F.], Faculty of Medicine, Osaka University, 2-2 Yamada-Oka, Suita, Osaka 565; and Department of Dermatology, Faculty of Medicine, Kobe University, Kobe, Hyogo 650 [M. U.], Japan

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 x 10⁵ to 1.8 x 10⁶ J/m², 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 242 (C TGC C CGC; Cys Arg) was specifically observed in both skin cancers and actinic keratoses. Furthermore, double or triple mutations were induced in all UVB-induced skin cancers and in three of eight actinic keratoses. Most of the mutations (17 of 20) occurred at dipyrimidine sites.

¹ This work was supported by grants from the Japanese Ministry of Education, Science and Culture, the Mitsubishi Foundation, Princess Takamatsu Cancer Research Fund, Cosmetology Research Foundation, and T. Kawai Memorial Fund for Radiation Biology.

² To whom requests for reprints should be addressed. Tel: 81-6-879-3810; Fax: 81-6-879-3819; E-mail: nomura@radbio.med.osaka-u.ac.jp.

Received 3/20/97. Accepted 4/15/97.

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