Radiosensitization and Anti-tumour Effects of Cytosine Deaminase and Thymidine Kinase Fusion Suicide Gene in Human Adenoid Cystic Carcinoma Cells

• Published in: Journal of international medical research Vol. 37; no. 2; pp. 479 - 490
• Main Authors: Huang, S-Y, Zhang, D-S, Han, J-Q, Zhang, N, Zhang, S-Z, Mu, W-L, Wei, F-C
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.03.2009
• Subjects: Artificial Gene Fusion; Blotting, Western; Carcinoma, Adenoid Cystic - genetics; Carcinoma, Adenoid Cystic - pathology; Cell Death - drug effects; Cell Death - radiation effects; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - radiation effects; Cytosine Deaminase - metabolism; Drug Screening Assays, Antitumor; Flucytosine - pharmacology; Ganciclovir - pharmacology; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - radiation effects; Genes, Transgenic, Suicide - drug effects; Genes, Transgenic, Suicide - radiation effects; Humans; Radiation Tolerance - drug effects; Radiation Tolerance - radiation effects; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Thymidine Kinase - metabolism; X-Rays; Ganciclovir; Radiosensitization; Suicide gene; 5-Fluorocytosine; Adenoid cystic carcinoma
• ISSN: 0300-0605; 1473-2300
• DOI: 10.1177/147323000903700224

Herpes simplex virus thymidine kinase (HSV-TK) and Escherichia coli cytosine deaminase (CD) can convert innocuous prodrugs into cytotoxic metabolites and are being investigated for use in gene therapy for cancer. Human adenoid cystic carcinoma (ACC-2) cells transduced with a CD/HSV-TK fusion gene (ACC-2/CD-TK cells) were found to be more sensitive to radiation than ACC-2 cells when exposed to 5-fluorocytosine (5-FC; 40 μg/ml) plus ganciclovir (0.1 μg/ml) for 48 h before irradiation. Analysis of radiation survival curves for cells exposed to 5-FC plus ganciclovir before irradiation showed that ACC-2 cells had a higher capacity for sublethal damage repair (Dq value) and greater cellular radiosensitivity (D0 value) than ACC-2/CD-TK cells. Colony formation rate after 2 Gy of irradiation was significantly greater for ACC-2 than for ACC-2/CD-TK cells when cells were treated with 5-FC plus ganciclovir before irradiation. This study, therefore, indicates that addition of radiation might substantially improve the therapeutic potential of CD-TK fusion gene therapy of human adenoid cystic carcinomas.