Abstract
It is well known that high LET radiation such as heavy ions is more effective than low LET radiation such as X and gamma rays for various biological effects. The RBE- LET curves had a peak in the LET range of 100 to 200 keV/µm even if the biological endpoints were different. To clarify the qualitative and quantitative difference in cellular and molecular effects between high- and low-LET radiations, we investigated the difference in mutation induction on the hprt locus in normal human fibroblasts irradiated with X rays (200kV, 20mA) and iron ions (500 MeV/n) with LET ranging from 200 to 400 keV/µm.
First, we 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 of 200 to 260 keV/µm were higher than 1, and the RBE for iron ions with LET ranging of 300 to 400 keV/µm were nearly 1. These results indicated that the mutation induction for iron ions decreased with increasing LET, and the mutation frequency of high LET region (over 300 keV/µm) was similar to X rays. Next, 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) were analyzed using the multiplex PCR. About 70% of mutant induced by iron ions showed deletion of the entire exons, while about 70% mutant induced by X rays showed partial deletion, which one or more exons are missing. The results indicated that iron ion induced mutants sustained severer damage than X rays induced mutant even if the dose response curves for mutation induction were similar between X rays and iron ions.
