[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.