Acta Vet. Brno 2009, 78: 205-217

Apoptosis and Senescence – Main Mechanisms of Accelerated Aging of Haematopoietic Cells after Irradiation

Jiřina Vávrová1, Martina Řezáčová2

1Department of Radiobiology, Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic
2Department of Medical Biochemistry, Faculty of Medicine in Hradec Králové, Charles University in Prague, Czech Republic

Received August 11, 2008
Accepted December 15, 2008

Haematopoietic stem cell (HSC) is one of the most radiosensitive cells in organism. In mice it is characterized as lin-Sca-1+CD117+ cell. This review discusses the role of HSC subpopulations in recovery of haematopoiesis after irradiation, and molecular mechanisms of reaction of HSC to damage induced by genotoxic stress, mainly to double strand breaks (DSB) of DNA. Various proteins are accumulated on the site of break, e.g. 53BP1 and γH2AX. Repair of the damage and related signalling is executed by many proteins, such as ATM, ATR, and DNA-PK kinases, MRN complex and proteins of homologous recombination and non-homologous end joining. Repetitive irradiation by low doses of ionizing radiation causes in HSC accumulation of proteins into so-called “ionizing radiation inducing foci” (detectable by γH2AX) and decreases repair capacity of HCS. Furthermore, two possible molecular mechanisms of HSC reaction to radiationinduced DNA damage are discussed – apoptosis and senescence. While majority of differentiated haematopoietic cells, leukaemic cells, and haematopoietic progenitors die after irradiation by apoptosis, in HSC also senescence was detected. It also seems that decrease in proliferative capacity of HSC related to old age is caused by accumulation of DNA damage induced by oxygen radicals in the pool of quiescent stem cells.