[Experimental treatment of brain tumor cells using CD suicide gene].
A negative selection system for glioma gene therapy was established in vitro. C 6 rat glioma cells were infected with recombined retrovirus which contain Escherichia coli cytosine deaminase (EC-CD) gene. The enzyme CD can transform the non-toxic prodrug 5-Fluorocytosine (5-FC) to the highly cellular toxic compound 5-Fluorouracil (5-FU). The growth inhibition studies proved that CD-positive cells were highly sensitive to 5-FC, the IC50 about 3 mumol/L, compared with an IC50 of approximately 6000 mumol/L in parental C 6 cells. Both CD-positive and negative cells were sensitive to 5-FU at very low concentration (IC50 < 1 mumol/L). Mixed cellular assay showed CD-positive cells had "bystander effect" on CD-negative cells when exposed to 5-FC. Our results demonstrate that EC-CD gene should be an efficient suicide gene for the treatment of glioma.
Shanghai Institute of Biochemistry, Academia Sinica.
L F
LF
Xu
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K
Ge
Z C
ZC
Zheng
L Y
LY
Sun
X Y
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Liu
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000473:pathology*; D043525:Cytosine Deaminase; D004926:Escherichia coli / Q000235:genetics; D005437:Flucytosine / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D005796:Genes; D015316:Genetic Therapy; D005910:Glioma / Q000473:pathology*; D009700:Nucleoside Deaminases / Q000235:genetics*; D051381:Rats; D012190:Retroviridae / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000964:Antimetabolites, Antineoplastic; D005437:Flucytosine; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase; D005472:Fluorouracil