The bone marrow (BM) is the primary organ in adults in which blood cell formation occurs. Hematopoiesis is orchestrated by a rare population of pluripotent stem cells, known as hematopoietic stem cells (HSCs). The maintenance of genomic stability is essential for cell survival and for preventing malignant transformation. DNA damage checkpoints and DNA repair mechanisms cooperate to restore genomic stability following genotoxic insult. Cytochrome C is one of the most important proapoptotic factors released in this process that interacts with apoptotic protease-activating factor 1 and deoxyadenosine triphosphate in the cytosol, collectively forming the apoptosome. Studies to date clearly indicate that mesenchymal stromal cells (MSCs) are radioresistant. Long-term proliferation of primary human MSCs in vitro following exposure to high-dose irradiation is comparable to that of known radioresistant cell types, such as the A549 lung cancer cell line. MSCs are radioresistant progenitors that reside in hypoxic niches in vivo, particularly in the BM.