The use of suicide gene systems in vascular cells in vitro.
To investigate the efficiency of suicide gene systems on vascular cells, HSV-tk/GCV and EC-CD/5-FC systems were established on vascular endothelial cells in vitro by retroviral transduction. Both modified cell lines were highly sensitive to prodrugs, the IC50 for GCV was less than 0.4 microM, and IC50 for 5-FC was less than 75 microM, while the parental endothelial cells were insensitive even at the highest concentrations of prodrugs in this experiment. Mixed cellular assay showed that significant bystander effect was exhibited in modified endothelial cells. When only 10% or 30% of the mixed cells were tk positive and exposed to 20 microM GCV for 6 days, more than 60% or 90% of the whole population was killed. Similar result was also found in CD positive cells. These results indicated that both HSV-tk/GCV and EC-CD/5-FC systems could efficiently suppress endothelial cell growth in vitro.
Xu
L F
LF
Shanghai Institute of Biochemistry, Chinese Academy of Sciences, China.
Xu
D H
DH
Ge
K
K
Zheng
Z C
ZC
Sun
L Y
LY
Liu
X Y
XY
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D043525:Cytosine Deaminase; D004730:Endothelium, Vascular / Q000166:cytology; D005437:Flucytosine / Q000633:toxicity*; D015774:Ganciclovir / Q000633:toxicity*; D005822:Genetic Vectors; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009700:Nucleoside Deaminases / Q000235:genetics; D011355:Prodrugs / Q000633:toxicity*; D012190:Retroviridae / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics
D011355:Prodrugs; D005437:Flucytosine; D013937:Thymidine Kinase; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase; D015774:Ganciclovir