Abstract |
To investigate the potential use of E. coli cytosine deaminase (CD) gene instead of the commonly used HSV-TK gene in the gene therapy of brain tumors, we constructed a retrovirus vector carrying the CD gene. We then transduced a rat glioma cell line C6 with CD gene by the retrovirus vector. Transduction of the CD gene made C6 cells become highly sensitive to the anti-fungi drug 5-fluorocytosine (5FC). IC50 for 5FC was 6,000 microM in CD-negative cells, while it was 3 microM in CD-positive cells. Mixed cellular assay showed that CD-positive cells had a strong "bystander effect" on CD-negative cells when exposed to 5FC. Significant anti- tumor effects were observed in nude mice bearing s.c. tumors derived from CD-positive cells when these animals were given 250 mg/kg 5FC twice a day for 20 consecutive days. A marked decrease in tumor weight occurred when a mixture containing 50% CD-positive and 50% CD-negative C6 cells was injected s.c., followed by 5FC treatment, suggesting the bystander effect in vivo. Concerning the pharmacokinetics of 5FC, especially its high oral bio-availability and good penetration into cerebrospinal fluid, we suppose that the combination of CD-gene transfer and 5FC oral administration may have potential use in the gene therapy of brain tumors.
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Authors | K Ge, L Xu, Z Zheng, D Xu, L Sun, X Liu |
Journal | International journal of cancer
(Int J Cancer)
Vol. 71
Issue 4
Pg. 675-9
(May 16 1997)
ISSN: 0020-7136 [Print] United States |
PMID | 9178825
(Publication Type: Journal Article)
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Chemical References |
- Antimetabolites, Antineoplastic
- Recombinant Fusion Proteins
- Flucytosine
- Nucleoside Deaminases
- Cytosine Deaminase
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Topics |
- Animals
- Antimetabolites, Antineoplastic
(pharmacology, therapeutic use)
- Brain Neoplasms
(drug therapy, enzymology, pathology)
- Cytosine Deaminase
- Drug Resistance, Neoplasm
(genetics)
- Flucytosine
(pharmacology, therapeutic use)
- Genetic Therapy
- Genetic Vectors
(administration & dosage)
- Glioma
(drug therapy, enzymology, pathology)
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Neoplasm Transplantation
- Nucleoside Deaminases
(genetics, metabolism)
- Rats
- Recombinant Fusion Proteins
(metabolism)
- Single-Blind Method
- Transfection
- Tumor Cells, Cultured
(drug effects)
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