PROTECTIVE ROLE OF GLUTATHIONE SYNTHESIS ON RADIATION-INDUCED DNA-DAMAGE IN RABBIT BRAIN

1. Radiotherapy has attracted increasing interest in recent years. It is known that ionizing radiation induces oxygen radical injury, wherea s oxidative stress by the radiation can cause cellular responses to de fense cellular injury. In this study, the metabolism of antioxidants i n response to ionizing radiation to the brain was studied in the brain using experimental rabbits. 2. Ionizing radiation to the hemicerebrum caused an increase in the levels of glutathione (GSH) and the activit y of a GSH synthesizing enzyme, gamma-glutamylcysteine synthetase (gam ma-GCS), and Cu,Zn-superoxide dismutase (Cu,Zn-SOD). Ionizing radiatio n also induced DNA-damage estimated by the formation of 8-hydroxydeoxy guanosine. These changes were dependent on the radiation dose. 3. Prev ious intrathecal-administration of buthionine sulfoximine (100 mu M), a specific inhibitor of gamma-GCS. increased DNA damage by radiation i n the radiated hemicerebrum. That of S-methyl GSH, on the other hand, resulted in a significant reduction of DNA damage by radiation. 4. The se results suggest that synthesis of GSH and Cu,Zn-SOD is responsive t o ionizing radiation and this induction of antioxidants may play a rol e in reducing tissue damage in radiotherapy.