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.