Qualitative and quantitative difference in mutation induction by X rays and iron ions

During space flight involving a long period of stay in the International Space Station (ISS), astronauts are exposed to cosmic rays, which includes high atomic number and high energy (HZE) charged particles. Biological effects, such as chromosomal aberrations, of iron ions were studied, while limited reports have been available about mutation induction in normal human cells induced by iron ions. In order to clarify the qualitative and quantitative difference of high- and low-LET radiations, we investigated the difference in mutation induction on the hprt locus in normal human fibroblasts irradiated with X rays and iron ions (500 MeV/n) with LET ranging from 200 to 400 keV/µm.We first showed the dose-response curves of mutation induction at hprt locus detected with 6-thioguanine resistant clones for X rays and iron ions, and calculated the RBE for iron ions relative to X rays. The RBE of the mutation frequency per total number of surviving cells for iron ions with LET ranging from 200 to 260 keV/µm were higher than 1, and the RBE for iron ions with LET ranging from 300 to 400 keV/µm were nearly 1. These results indicated that the mutation frequency of high LET region (over 300 keV/µm) was similar to X rays. Next we investigated the deletion spectrum of 9 exons in hprt locus of mutant colonies induced by X rays (1.5 - 2.4Gy) and 260 keV/µm iron ions (0.2 - 0.8Gy) analyzed using the multiplex PCR. About 70% of mutants induced by iron ions showed deletion of the entire exons, while about 70% of mutants induced by X rays showed partial deletion, which one or more exons were missing. The results indicated that iron-ion-induced mutants sustained severer damage than X-ray-induced mutants even if the dose response curves for mutation induction were similar between X rays and iron ions.日本宇宙生物科学会第23回大