Nagasawa Hatsumi, Little John B
Department of Cancer Cell Biology, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
Mutat Res. 2002 Oct 31;508(1-2):121-9. doi: 10.1016/s0027-5107(02)00193-8.
We have previously shown that when confluent cultures of mammalian cells are exposed to very low fluences of alpha particles, fluences whereby as few as 1% of the cell nuclei are traversed by a single particle, genetic effects including specific gene mutations and sister chromatid exchanges (SCE) are induced in neighboring, non-irradiated "bystander" cells. The present investigation was designed to examine the induction of chromosomal aberrations in wild-type CHO cells and its DNA double strand break repair deficient mutant xrs-5 by a broad range of alpha particle fluences yielding mean doses of 0.17-200cGy. The dose-response curve for the induction of aberrations was curvilinear for both cell lines, with a greater effect occurring at very low fluences owing to aberrations arising in bystander cells. These aberrations were predominantly of the chromatid-type. With such fluences, the number of cells with induced aberrations per nucleus irradiated increased up to 4-fold in CHO cells and 15-fold in xrs-5 cells over that expected if aberrations occurred only in irradiated cells. These results are discussed in terms of the hypothesis that the primary DNA damage in bystander CHO cells is oxidative base damage leading to a relatively small bystander effect for gross chromosomal aberrations as compared with mutations or SCE; the larger bystander effect in xrs-5 cells is the result of oxidative damage and non-repaired DNA strand breaks which may result from opposed oxidative lesions.
我们之前已经表明，当哺乳动物细胞的汇合培养物暴露于极低通量的α粒子时，即通量低至仅有1%的细胞核被单个粒子穿过时，在相邻的未受照射的“旁观者”细胞中会诱导出包括特定基因突变和姐妹染色单体交换（SCE）在内的遗传效应。本研究旨在通过一系列产生平均剂量为0.17 - 200 cGy的α粒子通量，研究野生型CHO细胞及其DNA双链断裂修复缺陷型突变体xrs - 5中染色体畸变的诱导情况。两种细胞系中畸变诱导的剂量 - 反应曲线均为曲线，由于旁观者细胞中出现的畸变，在极低通量时效应更大。这些畸变主要是染色单体型的。在这样的通量下，每个受照射细胞核中诱导出畸变的细胞数量，与仅在受照射细胞中发生畸变的预期情况相比，在CHO细胞中增加了4倍，在xrs - 5细胞中增加了15倍。我们根据以下假设对这些结果进行了讨论：旁观者CHO细胞中的主要DNA损伤是氧化性碱基损伤，与突变或SCE相比，这导致了对染色体畸变的旁观者效应相对较小；xrs - 5细胞中较大的旁观者效应是氧化性损伤和未修复的DNA链断裂的结果，这可能是由相反的氧化性损伤引起的。
