The viral protein apoptin induces apoptosis in UV-C-irradiated cells from individuals with various hereditary cancer-prone syndromes

Apoptin, a protein derived from chicken anemia virus, has previously been s hown to induce apoptosis in a p53-independent and Bcl-2-stimulated manner i n transformed and tumorigenic human cells but not in normal diploid human c ells, suggesting that it is a potential agent for tumor therapy, Here we re port that Apoptin can induce apoptosis in UV-C-irradiated diploid skin fibr oblasts from individuals with various hereditary cancer-prone syndromes tha t are characterized by a germ-line mutation in a tumor suppressor gene. The same effect is found when these cells are irradiated with X-rags, In contr ast, diploid skin fibroblasts from healthy donors or from individuals with DNA repair disorders are not responsive to Apoptin-induced apoptosis upon U V-C or X-ray irradiation, After transfection of untreated cells, Apoptin is found predominantly in the cytoplasm, whereas in UV-C-exposed Apoptin-resp onsive cancerprone cells, it migrates to the nucleus, where it causes rapid apoptosis, Apoptin remains localized in the cytoplasm after UV-C treatment of diploid cells from healthy individuals. The induction of apoptosis by A poptin in cancer-prone cells with a germ-line mutation in a tumor suppresso r gene is UV dose-dependent and transient, just like many other UV-induced processes. These results suggest that Apoptin mag be used as a diagnostic t ool for detection of individuals,vith an increased risk for hereditary canc er and premalignant lesions.