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Department of Immunology [L. A. A., H. N. A.], The University of Texas M. D. Anderson Cancer Center, and Department of Dermatology [L. H. G.], Baylor College of Medicine, Houston, Texas 77030, and Photocarcinogenesis Program [R. D. L.], Lovelace Medical Foundation, Albuquerque, New Mexico 87108
Basal cell nevus syndrome (BCNS) is an autosomal dominant genetic disorder in which the afflicted individuals are extremely susceptible to sunlight-induced skin cancers, particularly basal cell carcinomas. However, the cellular and molecular basis for BCNS is unknown. To ascertain whether there is any relationship between genetic predisposition to skin cancer and increased sensitivity of somatic cells from BCNS patients to killing by UV radiation, we exposed skin fibroblasts established from unexposed skin biopsies of several BCNS and age- and sex-matched normal individuals to either UV-B (280320 nm) or UV-C (254 nm) radiation and determined their survival. The results indicated that skin fibroblasts from BCNS patients were hypersensitive to killing by UV-B but not UV-C radiation as compared to skin fibroblasts from normal individuals. DNA repair studies indicated that the increased sensitivity of BCNS skin fibroblasts to killing by UV-B radiation was not due to a defect in the excision repair of pyrimidine dimers. These results indicate that there is an association between hypersensitivity of somatic cells to killing by UV-B radiation and the genetic predisposition to skin cancer in BCNS patients. In addition, these results suggest that DNA lesions (and repair processes) other than the pyrimidine dimer are also involved in the pathogenesis of sunlight-induced skin cancers in BCNS patients. More important, the UV-B sensitivity assay described here may be used as a diagnostic tool to identify presymptomatic individuals with BCNS.
1 Supported by a postdoctoral fellowship from the Meadows Foundation. Present address: Institut Suisse Experimentales de Recherches sur le Cancer, CH-1066, Epalinges, Lausanne, Switzerland.
2 To whom requests for reprints should be addressed, at Department of Immunology, Box 178, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.
Received 6/ 9/89. Revised 10/11/89. Accepted 10/27/89.
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