Japanese Journal of Veterinary Research;Volume 37, Number 3-4

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CYTOTOXIC EFFECT OF ACYCLOVIR ON CULTURED MAMMALIAN CELLS TO WHICH HERPESVIRUS THYMIDINE KINASE GENE WAS INTRODUCED

TANABE, Kiyoshi;HIRAOKA, Wakako;KUWABARA, Mikinori;SATO, Fumiaki;NARITA, Takahiro;NIIKURA, Masahiro

Permalink : http://hdl.handle.net/2115/3189
JaLCDOI : 10.14943/jjvr.37.3-4.181
KEYWORDS : acyclovir;herpesvirus thymidine kinase;cytotoxicity;phosphorylation;gene transfer

Abstract

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 concertration-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.

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