UV-RADIATION INDUCES DNA FRAGMENTATION AND CELL-DEATH IN B16 MELANOMASENSITIZED BY BROMODEOXYURIDINE - IMPAIRED C-JUN INDUCTION AND DEFECTIVE TYROSINE PHOSPHORYLATION SIGNALING

The relevance of tyrosine phosphorylation and c-jun protooncogene expr ession to radiation sensitization was investigated in B16 melanoma. Th ese cells are sensitized by bromodeoxyuridine (BrdU), a thymidine anal og, showing extensive DNA fragmentation reminiscent of apoptosis, afte r UV radiation. UV-irradiated unsensitized cells did not reveal DNA fr agmentation but showed increased expression of c-jun and greater prote in tyrosine phosphorylation in response to sodium vanadate, an inhibit or of tyrosine phosphatases. However, these responses were inhibited i n Uv-irradiated BrdU-treated cells. Our data suggest that the bromodeo xyuridine-induced sensitization to radiation can lead to DNA fragmenta tion and cell death, partly because of a defective tyrosine kinase sig nalling and an impaired c-jun expression, both of which appear importa nt for cell survival in response to UV radiation. (C) 1994 Academic Pr ess, Inc.