X 射线照射诱导的微核形成并不总是源于 DNA 双链断裂。

Micronuclei formation induced by X-ray irradiation does not always result from DNA double-strand breaks.

机构信息

Laboratory of Radiation Biology, Research Reactor Institute, Kyoto University, Japan.

出版信息

J Radiat Res. 2012;53(1):93-100. doi: 10.1269/jrr.11147. Epub 2012 Jan 13.

Abstract

X-ray induced formation of micronuclei is generally thought to result from DNA double-strand breaks (DSBs). However, DNA DSBs inhibit the cell cycle progression that is required for micronucleus formation. In order to reconcile this apparent discrepancy, we investigated whether DNA DSBs induced during the G1 phase could lead to micronucleus formation. We irradiated human embryonic (HE17) cells that had been treated with a radical scavenger, either DMSO or ascorbic acid (AsA), and determined the level of suppression of DNA DSBs or micronuclei. When DNA DSBs were evaluated using 53BP1 foci, treatment with 5 mM AsA did not inhibit the numbers of foci at various intervals after X-ray irradiation; however, treatment with 5 mM or 256 mM DMSO did have a significant inhibitory effect. By contrast, an assay of micronucleus numbers showed that treatment with 5 mM or 256 mM DMSO before X-ray irradiation resulted in almost no inhibition of micronucleus formation, but treatment with 5 mM AsA did have a significant inhibitory effect. These results clearly showed that AsA could suppress micronucleus formation, although it was not effective for suppression of DNA DSBs. Therefore, we conclude that DNA DSBs induced in the G1 phase do not directly lead to micronucleus formation.

摘要

X 射线诱导形成微核通常被认为是由于 DNA 双链断裂 (DSBs)。然而，DNA DSBs 抑制了微核形成所需的细胞周期进程。为了解决这一明显的矛盾，我们研究了在 G1 期诱导的 DNA DSB 是否会导致微核形成。我们用自由基清除剂 DMSO 或抗坏血酸 (AsA) 处理人胚胎 (HE17) 细胞，然后用 X 射线照射，测定 DNA DSBs 或微核的抑制水平。当用 53BP1 焦点评估 DNA DSBs 时，用 5 mM AsA 处理不会抑制 X 射线照射后不同时间的焦点数量；然而，用 5 mM 或 256 mM DMSO 处理则有显著的抑制作用。相比之下，微核数量的测定表明，用 5 mM 或 256 mM DMSO 处理后再用 X 射线照射，几乎不能抑制微核形成，但用 5 mM AsA 处理则有显著的抑制作用。这些结果清楚地表明，尽管 AsA 对抑制 DNA DSBs 没有效果，但它可以抑制微核形成。因此，我们得出结论，G1 期诱导的 DNA DSBs 不会直接导致微核形成。