Mechanisms of protection of hematopoietic stem cells from irradiation

Current therapies for the treatment of malignancies are associated with significant limitations to the hematopoietic system since chemotherapy and radiation therapy do not discriminate between normal and malignant cells. Since bone marrow depression occurs at low to midlethal doses of irradiation, approaches to improving the therapeutic index of treatment must include measures to enhance the sensitivity of the tumor relative to normal hematopoietic tissue or, by reducing toxicity to normal hematopoietic tissues leaving tumor resistance unchanged. Radioprotective agents have been proposed to unravel the fundamental processes by which radiation itself damages hematopoietic tissue. In radiotherapy, the importance of these agents is derived from their potential use as selective protectors against radiation damage to normal hematopoietic tissue such that higher doses of radiation can be delivered to tumors to achieve a therapeutic advantage. A variety of agents have been and are being evaluated as possible protectants. These include aminothiols, synthetic polysaccharides, vitamins and cytokines. This review attempts to summarize the role both chemical and biological response modifiers play as hematopoietic radioprotectors. In addition, possible mechanisms of protection of hematopoietic stem cells from irradiation are discussed.