Response of radio-sensitive mutant cell line against heavy-ion beams

Abstract

The high LET radiations are more effective to kill cells due to an induction of non-repairable dsb (double strand break). This study compared the effects of charged particles on cell killing in a pair of mouse cell lines which were normal or defective in the repair of DNA dsb. Charged particle beams were C ion, Ar ions, and Fe ion. Inactivation Cross Sections (ICS) were calculated from the comparison with the survival curves. In the dsb repair deficient cells, Relative Biological Effectiveness (RBE) values were close to unity for cell killing induced by charged particles with small Linear Energy Transfer (LET), and were even smaller than unity at the LET region larger than 300 keV/micro-m. The ICS increased with LET for both cell lines. The ICS of dsb repair deficient mutants was always larger than that of their parents for the all LET ranges. With increasing LET, the differences of ICS between the mutant and its parent become smaller. This suggests that the ratio of non-repairable dsb induced increases with increasing LET. However, dsb repair still took place at high LET regions in normal cell lines, even its efficiency is low. It has been argued that the DNA content and geometrical cross section of nuclei play important roles in cell inactivation by high LET radiations. Karyotypes of the both cell lines were near diploid. Chromosome number widely varied in SL3-147 cells. The average nuclear area of dsb repair deficient cells was also bigger than that of their parent cell line. These results suggest that DNA contents are not important for cell inactivation at high LET regions.

高LET放射は、修復不能なdsb(2本鎖切断)を多く作り出すために、細胞を殺すのにより効果的である。正常のネズミ細胞株と、DNA dsbの修復が出来ないネズミ細胞株の組に対して、細胞死に対する荷電粒子の効果を比較した。荷電粒子はC、ArとFeのイオンを用いる。活動阻害断面積(ICS)は生存線量との比較から計算される。dsb修復が出来ない細胞株中では、線エネルギー付与(LET)が小さい荷電粒子による細胞死については、生物学的効果比(RBE)値は1に近く、300keV/マイクロメートルを越える領域では1より小さかった。活動阻害断面積は両方の細胞株でLETとともに増加した。全てのLET領域において、dsb修復が不可能な突然変異体のICSは、常に母細胞より大きかった。LETの増加とともに、突然変異体と母細胞との間のICSの違いは小さくなった。このことはLETの増加とともに修復不可能なdsbの割合が増すことを示唆する。しかし、正常細胞株では高LET領域においても僅かながらdsb修復が起きていた。DNA量と核の幾何的断面積は高LET放射による細胞の活動阻害に大きく寄与すると論じられてきた。両方の細胞の核型は倍数体に近い。平均染色体数はSL3-147細胞の方がLTAより僅かに多かった。dsb修復欠損細胞の平均核領域はまた母細胞株のそれより大きかった。これらの結果は高LET領域における細胞の活動阻害に対してDNA量は重要でないことを示唆する。