, Volume 33, Issue 3, pp 189-194

Preferential radiosensitization of 9L glioma cells transduced with HSV-tk gene by acyclovir

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Abstract

The antiviral drug acyclovir, an analogue of purine,was found to selectively enhance the radiosensitivity ofrodent tumor cells which were transduced with theherpes simplex virus thymidine kinase gene (HSV-tk). 9Lrat glioma cells transduced with HSV-tk and treatedwith acyclovir (20 μg/ml) for 24 hr beforeor after irradiation were highly sensitive to radiation,as compared with non-transduced glioma cells. When 9Lcells transduced with HSV-tk gene were exposed toacyclovir and radiation, the sensitizer enhancement ratio (SER)was 1.6. In vivo, a significant increase inthe median survival time of rats with 9L-tktumors was observed when acyclovir was administered beforeand after single-dose irradiation, relative to the survivaltime of similar rats receiving radiation alone. Theresults show that an antiviral agent can selectivelyenhance cell killing by radiation in cells transducedwith the HSV-tk, and suggest that the additionof HSV-tk gene therapy to standard radiation therapywill improve the effectiveness of treatment for braintumors.