UV radiation induces DNA fragmentation and cell death in B16 melanoma sensitized by bromodeoxyuridine: impaired c-jun induction and defective tyrosine phosphorylation signalling.

The relevance of tyrosine phosphorylation and c-jun protooncogene expression to radiation sensitization was investigated in B16 melanoma. These cells are sensitized by bromodeoxyuridine (BrdU), a thymidine analog, showing extensive DNA fragmentation reminiscent of apoptosis, after UV radiation. UV-irradiated unsensitized cells did not reveal DNA fragmentation but showed increased expression of c-jun and greater protein tyrosine phosphorylation in response to sodium vanadate, an inhibitor of tyrosine phosphatases. However, these responses were inhibited in UV-irradiated BrdU-treated cells. Our data suggest that the bromodeoxyuridine-induced sensitization to radiation can lead to DNA fragmentation and cell death, partly because of a defective tyrosine kinase signalling and an impaired c-jun expression, both of which appear important for cell survival in response to UV radiation.