PMID: 9178825May 16, 1997Paper

Transduction of cytosine deaminase gene makes rat glioma cells highly sensitive to 5-fluorocytosine

International Journal of Cancer. Journal International Du Cancer
K GeX Liu

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 us...Continue Reading

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Dec 15, 2010·Future Oncology·Erik Hp van PuttenMartine Lm Lamfers
Feb 27, 2010·Experimental Cell Research·Yingbin YangK L Paul Sung
Dec 2, 1999·Journal of the National Cancer Institute·J C Morris
May 15, 2002·Archives of Pharmacal Research·Henry J LeeDong-Hoon Ko
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Nov 30, 2019·Neurosurgical Review·Ryota TamuraMasahiro Toda
May 5, 2001·Brain Research. Brain Research Reviews·M Bredel

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