Increased Hematopoietic Stem Cells/Hematopoietic Progenitor Cells Measured as Endogenous Spleen Colonies in Radiation-Induced Adaptive Response in Mice (Yonezawa Effect)

The phenomenon that a priming low dose of ionizing radiation (IR) induces resistance against a challenge IR at higher doses is called radiation-induced adaptive response (AR). The existence of AR was reported in varied biosystems in vitro, in utero and in vivo. In mice, the AR model, which was named generally as “Yonezawa Effect”, was originally established using low LET X-rays as both the priming IR and the challenge IR and rescue of bone marrow death as the endpoint. The underlying mechanism was due to the priming IR-induced resistance in the blood forming tissues. In a series of investigations in our laboratory under similar setup (i.e., using low LET X-rays as both the priming IR and the challenge IR, and rescue of bone marrow death as the endpoint), we first verified and confirmed the existence of AR in mice. Then, we further demonstrated the existence of AR by using different types of IR (i.e., low LET X-rays and high LET heavy ion particles), including 1) low LET X-rays as the priming IR and high LET heavy ion IR (carbon, neon, and silicon particles) as the challenge IR, and 2) high LET heavy ion IR (carbon particles) as the priming IR and low LET X-rays or high LET heavy ion IR (carbon and neon particles) as the challenge IR. In this paper, we validated the hematopoietic stem cells measured as endogenous colony forming units-spleen (CFU-S) under AR inducible and uninducible conditions using combination of low LET X-rays and high LET heavy ion IR as priming and challenge IR. We confirmed the consistency of CFU-S number change with the AR induction conditions, namely, under AR inducible conditions significantly increased number of CFU-S was observed while under AR uninducible conditions no markedly increased number of CFU-S was found. These findings suggest that AR in mice induced either by low LET X-rays against high LET heavy ion IR or by high LET heavy ion IR against low LET X-rays or high LET heavy ion IR would share at least in part a common underlying mechanism, namely, the priming IR-induced resistance in the blood forming tissues, leading to a protective effect on the hematopoietic stem cells, which may play an important role in rescuing the animals from bone marrow death. These findings bring new knowledge to the characterization of the Yonezawa Effect by providing a new insight into the mechanistic study on AR in vivo