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

• Published in: International journal of cancer 1999-07, Vol.82 (2), p.293-297
• Main Authors: Blackburn, Robert V., Galoforo, Sandra S., Corry, Peter M., Lee, Yong J.
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Animals; Antimetabolites - pharmacology; Antimetabolites, Antineoplastic - pharmacology; Antiviral Agents - pharmacology; Biological and medical sciences; Biotechnology; Carcinoma - pathology; Carcinoma - radiotherapy; Carcinoma - therapy; Cytomegalovirus - genetics; Cytosine Deaminase; Flucytosine - pharmacology; Fundamental and applied biological sciences. Psychology; Ganciclovir - pharmacology; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Viral; Gene therapy; Genetic Therapy; Genetic Vectors - genetics; Health. Pharmaceutical industry; Humans; Industrial applications and implications. Economical aspects; Male; Nucleoside Deaminases - genetics; Prodrugs - pharmacology; Promoter Regions, Genetic; Prostatic Neoplasms - pathology; Prostatic Neoplasms - radiotherapy; Prostatic Neoplasms - therapy; Radiation Tolerance - drug effects; Radiation Tolerance - genetics; Rats; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Thymidine Kinase - genetics; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - radiation effects
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19990719)82:2<293::AID-IJC22>3.0.CO;2-H

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. Int. J. Cancer 82:293–297, 1999. © 1999 Wiley‐Liss, Inc.