MECHANISMS OF PROTECTION OF HEMATOPOIETIC STEM-CELLS FROM IRRADIATION

Current therapies for the treatment of malignancies are associated wit h significant limitations to the hematopoietic system since chemothera py and radiation therapy do not discriminate between normal and malign ant cells. Since bone marrow depression occurs at low to midlethal dos es of irradiation, approaches to improving the therapeutic index of tr eatment must include measures to enhance the sensitivity of the tumor relative to normal hematopoietic tissue or, by reducing toxicity to no rmal hematopoietic tissues leaving tumor resistance unchanged. Radiopr otective agents have been proposed to unravel the fundamental processe s by which radiation itself damages hematopoietic tissue. In radiother apy, the importance of these agents is derived from their potential us e as selective protectors against radiation damage to normal hematopoi etic tissue such that higher doses of radiation can be delivered to tu mors to achieve a therapeutic advantage. A variety of agents have been and are being evaluated as possible protectants. These include aminot hiols, synthetic polysaccharides, vitamins and cytokines. This review attempts to summarize the role both chemical and biological response m odifiers play as hematopoietic radioprotectors. In addition, possible mechanisms of protection of hematopoietic stem cells from irradiation are discussed.