Selective enhancement of radiation response of herpes simplex virus thymidine kinase transduced 9L gliosarcoma cells in vitro and in vivo by antiviral agents
- Henry Ford Hospital, Detroit, MI (United States); and others
The purpose of this investigation was to demonstrate in a well-characterized tumor model that the radiosensitivity of tumor cells transduced with a herpes simplex virus thymidine kinase gene (HS-tk) would be selectively enhanced by antiviral agents. Rat 9L gliosarcoma cells transduced with a retroviral vector containing an HS-tk gene, 9L-tk cells were exposed to various doses or irradiation under either in vitro or in vivo conditions. The radiation sensitizing potential of two antiviral drugs, bromovinyl deoxyuridine (BVdU) and dihydroxymethyl ethyl methyl guanine (acyclovir), was evaluated in vitro. The radiosensitizing ability of BVdU was also evaluated with a 9L-tk tumor growing in the rat brain. Tumors growing in the right hemisphere of rat brains were irradiated stereotactically with single-dose irradiation. The radiation response of 9L-tk cells was selectively enhanced by antiviral agents relative to nontransduced cells. In the cell culture, when a 24-h drug exposure (20 {mu}g/ml) preceded radiation, the sensitizer enhancement ratio (SER) for BVdU and acyclovir was 1.4 {plus_minus} 0.1 and 1.3 {plus_minus} 0.1, respectively. Exposure of cells to 10 {mu}g/ml acyclovir for two 24-h periods both pre- and postirradiation resulted in a SER of 1.6 {plus_minus} 0.1. In vivo, a significant increase in median survival time of rats with 9L-tk tumors was found when BVdU was administered prior to single-dose irradiation relative to the survival time of similar rats receiving radiation alone. An antiviral agent can enhance cell killing by radiation with selective action in cells transduced with the herpes simplex virus thymidine kinase gene. The results suggest that the three-pronged therapy of HS-tk gene transduction, systemically administered antiviral drug, and stereotactically targeted radiation therapy will improve the effectiveness of radiation therapy for the treatment of radioresistant tumors. 25 refs., 6 figs.
- OSTI ID:
- 456772
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 33, Issue 4; Other Information: PBD: 1 Nov 1995
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
APPLIED STUDIES
55 BIOLOGY AND MEDICINE
BASIC STUDIES
SARCOMAS
BIOLOGICAL MODELS
COMBINED THERAPY
TUMOR CELLS
RADIOSENSITIVITY
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
CELL KILLING
SURVIVAL TIME
CELL PROLIFERATION
GENES
GENE REGULATION
GLIOMAS
EVALUATION
SENSITIZERS
HERPES SIMPLEX
PHOSPHOTRANSFERASES
THYMIDINE
DRUGS