Cytotoxic effect of acyclovir on cultured mammalian cells to which herpesvirus thymidine kinase gene was introduced.
The cytotoxic effects of acyclovir, which is a purine nucleoside analogue and is known as an antibiotic substance, were examined on three lines of rat skin fibroblast FR cells; normal FR cells, FRtk- cells which are deficient in the activity of thymidine kinase (tk) and FRtk-HSVtk+ cells which were prepared by introducing herpes simplex virus' tk gene to FRtk- cells. When FRtk-HSVtk+ cells growing exponentially were incubated in the presence of acyclovir for 4 h, the surviving fractions of the cells decreased in a concentration-dependent manner. Whereas, decrease of the surviving fractions was almost indiscernible in both FR cells and FRtk- cells at the whole ranges of drug-concentrations tested. These results indicate that acyclovir is phosphorylated by the herpes simplex virus' tk and becomes toxic to FRtk-HSVtk+ cells. This also means that FRtk-HSVtk+ cells are useful for the investigation of the biological activity of nucleoside analogues.
Tanabe
K
K
Hiraoka
W
W
Kuwabara
M
M
Sato
F
F
Narita
T
T
Niikura
M
M
D000212:Acyclovir / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D005347:Fibroblasts; D010766:Phosphorylation; D051381:Rats; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*
D013937:Thymidine Kinase; D000212:Acyclovir