1. Radiosensitization and anti-tumour effects of cytosine deaminase and thymidine kinase fusion suicide gene in human adenoid cystic carcinoma cells.
- Author
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Huang SY, Zhang DS, Han JQ, Zhang N, Zhang SZ, Mu WL, and Wei FC
- Subjects
- Blotting, Western, Carcinoma, Adenoid Cystic genetics, Cell Death drug effects, Cell Death radiation effects, Cell Line, Tumor, Cell Survival drug effects, Cell Survival radiation effects, Drug Screening Assays, Antitumor, Flucytosine pharmacology, Ganciclovir pharmacology, Gene Expression Regulation, Neoplastic drug effects, Gene Expression Regulation, Neoplastic radiation effects, Humans, RNA, Messenger genetics, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, X-Rays, Artificial Gene Fusion, Carcinoma, Adenoid Cystic pathology, Cytosine Deaminase metabolism, Genes, Transgenic, Suicide drug effects, Genes, Transgenic, Suicide radiation effects, Radiation Tolerance drug effects, Radiation Tolerance radiation effects, Thymidine Kinase metabolism
- Abstract
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 microg/ml) plus ganciclovir (0.1 microg/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 (D(q) value) and greater cellular radiosensitivity (D(0) 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.
- Published
- 2009
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