Studies on mechanism of tissue recovery by protective agents

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Recently many cytokines have been cloned as human recombinant (rH) and biological response modifiers (BRM) have been became available to human application. Such substances may be useful as radioprotective agents for human or improvement of hematopoietic radiation hazards which were induced during radiotherapy of cancer.The objective of this report is to investigate radioprotective responses of some cytokines (rH-IL-1, rH-IL-6, rH-G-CSF), BRM (LO908, OK-432, Itoposide) and other agents in order to contribute further to improvement of hematopoietic radiation injury in radiotherapy of cancer.Radioprotective activity for survivals of irradiated mice and enhancement of recovery for CFU-S or GM-CFC of marrow or spleen in irradiated mice by LO9018 and OK-432 were demonstrated when they were injected into mice 1 hr before irradiation. The injection of Itoposide into irradiated mice resulted in enhancement of recovery for the marrow cells. When rH-IL-1 was injected into mice 1 hr before irradiation or rH-IL-6 was injected into mice 1 hr after irradiation with a dose of 3 Gy, complete recovery from radiation injurys of hematopoietic stem cells was observed 7 days after the irradiations. Almost similar results were obtained for mice administered with rH-G-CSF. Radioprotective activity of mice by 5-FU was discovered when it was injected into mice 5 days before irradiation. The radiation source above used was low LET radiation. However, we also found out a radioprotective agent of WR151327 which was useful for high LET radiation. Studies on a new promising agent(ZR-14) for radioprotection is in progress.