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.
Rieber
M S
MS
Instituto Venezolano de Investigaciones Científicas (IVIC) Tumor Cell Biology Laboratory, Caracas, Venezuela.
Rieber
M
M
D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects / Q000528:radiation effects*; D004988:Ethers, Cyclic / Q000494:pharmacology; D016758:Genes, jun / Q000187:drug effects / Q000528:radiation effects*; D015151:Immunoblotting; D008546:Melanoma, Experimental; D051379:Mice; D019319:Okadaic Acid; D010766:Phosphorylation; D019000:Phosphotyrosine; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014466:Ultraviolet Rays; D014638:Vanadates / Q000494:pharmacology
D004273:DNA, Neoplasm; D004988:Ethers, Cyclic; D016755:Proto-Oncogene Proteins c-jun; D011838:Radiation-Sensitizing Agents; D019319:Okadaic Acid; D019000:Phosphotyrosine; D014638:Vanadates; D014443:Tyrosine; D017027:Protein Tyrosine Phosphatases; D001973:Bromodeoxyuridine