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 adenovirus containing a fusion gene encoding the Escherichia coli cytosine deaminase and herpes simplex virus type-1 thymidine kinase under the control of a cytomegalovirus promoter. Expression levels of the fusion protein were dependent on the multiplicity of infection used and incubation time following infection. PC-3 cells expressing this protein were sensitized to killing by the normally innocuous prodrugs 5-fluorocytosine and ganciclovir. In addition, radiation-induced killing was enhanced in virally infected cells in the presence of the prodrugs.
Blackburn
R V
RV
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48073-6769, USA.
Galoforo
S S
SS
Corry
P M
PM
Lee
Y J
YJ
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D002277:Carcinoma / Q000473:pathology* / Q000532:radiotherapy / Q000628:therapy; D003587:Cytomegalovirus / Q000235:genetics; D043525:Cytosine Deaminase; D005437:Flucytosine / Q000494:pharmacology*; D015774:Ganciclovir / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D008297:Male; D009700:Nucleoside Deaminases / Q000235:genetics*; D011355:Prodrugs / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000532:radiotherapy / Q000628:therapy; D011836:Radiation Tolerance / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013937:Thymidine Kinase / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D000963:Antimetabolites; D000964:Antimetabolites, Antineoplastic; D000998:Antiviral Agents; D011355:Prodrugs; D011993:Recombinant Fusion Proteins; D005437:Flucytosine; D013937:Thymidine Kinase; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase; D015774:Ganciclovir