Details
Zusammenfassung: <jats:p> 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 (D<jats:sub>q</jats:sub> value) and greater cellular radiosensitivity (D<jats:sub>0</jats:sub> 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. </jats:p>
Umfang: 479-490
ISSN: 0300-0605
1473-2300
DOI: 10.1177/147323000903700224