Nagasawa H, Peng Y, Wilson P F, Lio Y-C, Chen D J, Bedford J S, Little J B
Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado 80523, USA.
Radiat Res. 2005 Aug;164(2):141-7. doi: 10.1667/rr3420.
The bystander effect for sister chromatid exchanges (SCEs) and chromosomal aberrations was examined in hamster cell lines deficient in either DNA-PKcs (V3 cells, deficient in nonhomologous end joining, NHEJ) or RAD51C (irs3 cells, deficient in homologous recombination, HR). Cells synchronized in G0/G1 phase were irradiated with very low fluences of alpha particles such that < 1% of the nuclei were traversed by an alpha particle. Wild-type cells showed a prominent bystander response for SCE induction; an even greater effect was observed in V3 cells. On the other hand, no significant induction of SCE was observed in the irs3 RAD51C-deficient bystander cells irradiated at various stages in the cell cycle. Whereas a marked bystander effect for chromosomal aberrations occurred in V3 cells, the induction of chromosomal aberrations in irs3 bystander cells was minimal and similar to that of wild-type cells. Based on these findings, we hypothesize that HR is essential for the induction of SCE in bystander cells; however, HR is unable to repair the DNA damage induced in NHEJ-deficient bystander cells that leads to either SCE or chromosomal aberrations.
在缺乏DNA-PKcs(V3细胞,缺乏非同源末端连接,NHEJ)或RAD51C(irs3细胞,缺乏同源重组,HR)的仓鼠细胞系中,研究了旁观者效应在姐妹染色单体交换(SCE)和染色体畸变中的作用。将处于G0/G1期同步化的细胞用极低剂量的α粒子照射,使得<1%的细胞核被α粒子穿过。野生型细胞在SCE诱导方面表现出显著的旁观者反应;在V3细胞中观察到了更大的效应。另一方面,在细胞周期不同阶段照射的irs3 RAD51C缺陷型旁观者细胞中,未观察到SCE的显著诱导。虽然在V3细胞中发生了明显的染色体畸变旁观者效应,但irs3旁观者细胞中染色体畸变的诱导最小,与野生型细胞相似。基于这些发现,我们推测HR对于旁观者细胞中SCE的诱导至关重要;然而,HR无法修复在NHEJ缺陷型旁观者细胞中诱导的DNA损伤,这些损伤会导致SCE或染色体畸变。