Adenoviral transduction of a cytosine deaminase thymidine kinase fusion gene into prostate carcinoma cells enhances prodrug and radiation sensitivity

Prostate tumor cells (PC-3) were transduced with defective, recombinant ade novirus containing a fusion gene encoding the Escherichia coil cytosine dea minase and herpes simplex virus type-1 thymidine kinase under the control o f a cytomegalovirus promoter. Expression levels of the fusion protein were dependent on the multiplicity of infection used and incubation time followi ng infection. PC-3 cells expressing this protein were sensitized to killing by the normally innocuous prodrugs 5-fluorocytosine and ganciclovir. In ad dition, radiation-induced killing was enhanced in virally infected cells in the presence of the prodrugs. (C) 1999 Wiley-Liss, Inc.