Radiosensitization and anti-tumour effects of cytosine deaminase and thymidine kinase fusion suicide gene in human adenoid cystic carcinoma cells.
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.
Huang
S-Y
SY
Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Tongji University, Shanghai, China.
Zhang
D-S
DS
Han
J-Q
JQ
Zhang
N
N
Zhang
S-Z
SZ
Mu
W-L
WL
Wei
F-C
FC
D019677:Artificial Gene Fusion; D015153:Blotting, Western; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D043525:Cytosine Deaminase / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D005437:Flucytosine / Q000494:pharmacology; D015774:Ganciclovir / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D041722:Genes, Transgenic, Suicide / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects / Q000528:radiation effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013937:Thymidine Kinase / Q000378:metabolism*; D014965:X-Rays
D012333:RNA, Messenger; D005437:Flucytosine; D013937:Thymidine Kinase; D043525:Cytosine Deaminase; D015774:Ganciclovir