Morimoto Shigeko, Honma Masamitsu, Yatagai Fumio
Division of Radioisotope Technology, The Institute of Physical and Chemical Research (RIKEN), Saitama 351-0198, Japan.
J Radiat Res. 2002 Dec;43 Suppl:S163-7. doi: 10.1269/jrr.43.s163.
A molecular analysis of the loss of heterozygosity (LOH) events in human cells after low-dose heavy-ion exposure could contribute to the sensitive detection of the genetic influences caused by high-LET radiation. We exposed human lymphoblastoid TK6-20C cells to 10 cGy of an accelerated C-ion (22 keV/microm) beam, and observed a 3.1-fold increase in the mutation frequency (MF) at the heterozygous thymidine kinase (TK) locus over the background level. This increase was due to the induction of TK mutants exhibiting hemizygous-type LOH. Surprisingly, the frequency of type-2 hemizygous LOHs (interstitial deletions) was about 23-fold, induced over the background level, and the LOH extent patterns of this type 2 induced after the irradiation were clearly different from that of the spontaneous background.. Since hemizygous-type LOH mutants are considered to be the result of the end-joining repair of DNA double-strand breaks (DSB), C-ions may more efficiently induce DSBs than X-rays in this low-dose region. In addition, an enhanced misrepair of C-ion-induced DSBs might also account for the induction of radiation-specific hemizygous-type LOH.
对低剂量重离子照射后人细胞中杂合性缺失（LOH）事件进行分子分析，可能有助于灵敏检测高传能线密度（LET）辐射引起的遗传影响。我们将人淋巴母细胞TK6 - 20C细胞暴露于10 cGy的加速碳离子（22 keV/μm）束下，观察到在杂合胸苷激酶（TK）位点的突变频率（MF）比背景水平增加了3.1倍。这种增加是由于诱导出了表现为半合子型LOH的TK突变体。令人惊讶的是，2型半合子LOH（中间缺失）的频率比背景水平诱导增加了约23倍，并且照射后诱导的这种2型LOH范围模式与自发背景明显不同。由于半合子型LOH突变体被认为是DNA双链断裂（DSB）末端连接修复的结果，在这个低剂量区域，碳离子可能比X射线更有效地诱导DSB。此外，碳离子诱导的DSB修复错误增强也可能是辐射特异性半合子型LOH诱导的原因。
