Relieved residual damage in the hematopoietic system of mice rescued by radiation-induced adaptive response (Yonezawa Effect)

Abstract

Existence of adaptive response (AR) was previously demonstrated in C57BL/6J mice. Irradiations were performed by delivering a priming low dose of X-rays (0.50 Gy) in combination with a challenge high dose of accelerated carbon or neon ion particles. AR was characterized by significantly decreased mortality in the 30-day survival test. This mouse AR model ('Yonezawa Effect') was originally established by using X-rays as both the priming and challenge irradiations. The underlying mechanism was due to radio-resistance occurring in blood-forming tissues. In this study, we verified the existence of AR and further investigated residual damage in the hematopoietic system in surviving animals. Results showed that the priming low dose of X-rays could relieve the detrimental effects on the hematopoietic system. We observed both an improvement in the blood platelet count and the ratio of polychromatic erythrocytes (PCEs) to the sum of PCEs and normochromatic erythrocytes (NCEs) and a marked reduction of the incidences of micronucleated PCEs and micronucleated NCEs. These findings suggest that the priming low dose of low linear energy transfer (LET) X-rays induced a protective effect on the hematopoietic system, which may play an important role in both rescue from acute lethal damage (mouse killing) and prevention of late detrimental consequences (residual anhematopoiesis and delayed genotoxic effects) caused by exposure to a high challenge dose from low-LET (X-ray) or high-LET (carbon and neon ion) irradiations. These findings provide new knowledge of the characterization of the Yonezawa Effect by providing new insight into the mechanistic study of AR in vivo.

Fig. 1.

Effect of a priming dose of 0.50-Gy X-rays on a challenge dose of 7.50-Gy X-rays on 30-day survival of mice.

Fig. 2.

Effect of a priming dose of 0.50-Gy X-rays on a challenge dose of 6.50-Gy carbon, 5.50-Gy neon or 5.75-Gy carbon on 30-day survival of mice.

Fig. 3.

Effect of a priming dose of 0.50-Gy X-rays on a challenge dose of 7.50-Gy X-rays, 6.50-Gy carbon, 5.50-Gy neon or 5.75-Gy carbon on the femur bone marrow of mice.

Fig. 4.

Effect of a priming dose of 0.50-Gy X-rays on a challenge dose of 7.50-Gy X-rays, 6.50-Gy carbon, 5.50-Gy neon or 5.75-Gy carbon on the blood platelet count in the peripheral blood of mice. **Indicates statistically significant differences (P < 0.01) between the two groups that were compared.