COSPAR2018: FISH analysis of chromosomal aberrations induced by accelerated heavy iron particles in mouse splenocytes.

Purpose: High atomic number and energy (HZE) particles such as iron-56 (Fe) ions are a major contributor to health risks in long-term manned space exploration. To understand radiation-induced differential genotoxic effects between high linear energy transfer (LET) HZE particles and low LET photons, ground-based experiments were carried out at the National Institute of Radiological Sciences (NIRS) using total body irradiation (TBI) of mice with accelerated Fe particles generated by the Heavy Ion Medical Accelerator in Chiba (HIMAC). Materials and Methods: C57BL/6J Jms strain female mice of 8 weeks old were treated in accordance with the Guidelines for the Care and Use of Laboratory Animals established by NIRS. TBI was performed at a dose ranging from 0.1 to 3.0 Gy for Fe particles (500 MeV/nucleon, 200 keV/m), or from 0.1 to 5.0 Gy for X-rays (200 kVp, 0.50 mm Al+0.50 mm Cu filter). At one or two months after TBI, splenocytes were isolated and cultured in the presence of mitogens for 24 h. Colcemid was added to the last 2 h of the culture. Metaphase chromosome spreads prepared from splenocytes were painted with the fluorescence in situ hybridization (FISH) probes for chromosomes 1 (green), 2 (red) and 3 (yellow). Chromosomal aberrations (CAs) visualized by FISH were classified as translocations, insertions, dicentrics, and acentric fragments. Results and Conclusions: The present study is still in progress and observation of CAs is ongoing. Induction of CAs was detected at 0.5 Gy and higher doses of both X-rays and Fe particles. For each mouse, among all types of CAs translocations were around 90%. Fe particles didn’t induce CAs as frequently as X-rays. X-rays were 5 times more effective to induce translocations than Fe particles as compared at 3 Gy. The frequencies of unstable-type CAs didn’t show dose dependency at high dose and decreased with time. It is probable that DNA double-strand breaks induced by Fe particles are hardly rejoined and cause cell cycle arrest or cell death rather than lead to induction of CAs. Funding: Ministry of Education, Culture, Sports, Science and Technology (MEXT) Grant-in-Aid for Scientific Research on Innovative Areas, Grant Number 15H05935 “Living in Space”.COSPAR 2018 （42nd Assembly, 60th Anniversary