Induction of genotoxicity by accelerated heavy iron particles in the hematopoietic system in mice.

Purpose: The genotoxicity induced by high LET iron particles was studied and compared to that by low LET X-rays in the ground-based experiments carried out at NIRS using total body irradiation (TBI) of mice with the Heavy Ion Medical Accelerator in Chiba (HIMAC) and an X-ray generator (Pantak 320S, Shimadzu).Materials and Methods: C57BL/6J Jms strain female mice of 8 weeks old were used. TBI was performed at a dose ranging from 0.1 to 3.0 Gy for iron particles (500 MeV/nucleon, 200 keV/μm), or from 0.1 to 5.0 Gy for X-rays (200 kVp, 0.5 mm Al + 0.5 mm Cu filter). The RBE of iron particles to X-rays for induction of acute genotoxicity and late residual damage in the hematopoietic system was determined respectively at one and two months after TBI using the frequency of micronuclei in bone marrow erythrocytes as the endpoint. The health condition (body weight gain and the hemogram of the peripheral blood) was also investigated. Animals were treated in accordance with the Guidelines for the Care and Use of Laboratory Animals established by NIRS.Results and Conclusions: Reduction of body weight gain after TBI was in a similar way observed in the groups exposed to high doses from iron particles or X-rays. X-rays caused more efficiently hematological abnormality than iron particles. Iron particles and X-rays reduced the ratio of polychromatic erythrocytes (PCEs) to PCEs plus normochromatic erythrocytes (NCEs), an indicator for bone marrow proliferation, in a similar way, while iron particles resulted in more efficiently micronucleated PCEs and NCEs at low doses than X-rays. The relative effectiveness of iron particles to X-rays for induction of genotoxicity in bone marrow erythrocytes was higher at a low dose (0.5 Gy) than that at a high dose (3.0 Gy).Acknowledgments: This work was partially supported by both the Ministry of Education, Culture, Sports, Science and Technology (MEXT) Grant-in-Aid for Scientific Research on Innovative Areas, Grant Number 15H05935 “Living in Space” and three HIMAC Research Project Grants (22B258, 14J286 and 16J295). The expert technical assistance and administrative support of Ms. Hiromi Arai, Mr. Sadao Hirobe, Ms. Mikiko Nakajima, and Ms. Yasuko Morimoto are gratefully acknowledged.COSPAR 2018 （42nd Assembly, 60th Anniversary