Human glioma cells expressing herpes simplex virus thymidine kinase gene treated with acyclovir, ganciclovir and bromovinyldeoxyuridine. Evaluation of their activity in vitro and in nude mice.

Human glioma cell lines 8-MG-BA and 42-MG-BA were infected with retrovirus vector containing the herpes simplex virus thymidine kinase (HSVtk) gene. The effect of acyclovir (ACV), ganciclovir (GCV), and bromovinyldeoxyuridine (BVDU) on both, parental and HSVtk expressing glioma cells was studied in vitro. BVDU displayed the most potent cytotoxic properties in HSVtk-containing cells, however bystander killing of nontransduced parental cells in a mixture with HSVtk-containing cells was less potent, than observed for ACV or GCV. Taking into account the cytotoxic effect of different prodrugs used, as well as their ability to kill nontransduced bystander cells, ganciclovir was shown to be the most effective. Therefore the effect of GCV treatment on 8-MG-BA xenografts inoculated with PA-317JH5cl13 virus producer cells was further studied on nude mice.