Translocations are induced in hematopoietic stem cells after irradiation of fetal mice.

Translocations are induced in hematopoietic stem cells after irradiation of fetal mice.
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胎儿小鼠受到辐射后,造血干细胞中会诱导易位。

DOI:
10.1093/jrr/rrac078
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发表时间:
2023-01-20
影响因子:
2
通讯作者:
--
中科院分区:
医学4区
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--
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虽然哺乳动物胎儿被认为对辐射敏感,但在子宫内暴露于原子弹(A-Bomb)并作为成年人进行检查的幸存者的血淋巴细胞中,没有观察到易位频率的增加。由于用小鼠和大鼠的造血细胞进行的实验证实了这一发现,因此可以假设,要么照射后的胎儿造血干细胞(f-HSCs)不能产生交换型染色体异常,要么带有诱导异常的细胞在动物成年前就被消除了。本研究用2GyX射线照射孕鼠(产后12.5~15.5天),24小时后分离出长期HSCs。体外扩增的LT-HSC克隆的多色荧光原位杂交(MFISH)分析显示,43个胎儿克隆中有9个(21%)发生易位,41个母亲克隆中有21个(51%)易位。这些结果表明,在X射线照射24小时后,小鼠的f-HSCs中可以出现易位的细胞,但存在的频率低于母亲。因此,似乎很可能产生了携带易位的f-HSCs,但随后又消失了,因此淋巴细胞易位的频率可能会降低,并在动物成年时达到控制水平。
Although mammalian fetuses have been suggested to be sensitive to radiation, an increased frequency of translocations was not observed in blood lymphocytes from atomic bomb (A-bomb) survivors who were exposed to the bomb in utero and examined as adults. Since experiments using hematopoietic cells of mice and rats confirmed this finding, it was hypothesized that either irradiated fetal hematopoietic stem cells (f-HSCs) cannot generate exchange-type chromosomal aberrations or cells bearing induced aberrations are eliminated before the animals reach adulthood. In the present study, pregnant mice (12.5–15.5 days post coitum [dpc]) were irradiated with 2 Gy of X-rays and long-term HSCs (LT-HSCs) were isolated 24 h later. Multicolor fluorescence in situ hybridization (mFISH) analysis of LT-HSC clones proliferated in vitro showed that nine out of 43 (21%) clones from fetuses and 21 out of 41 (51%) clones from mothers bore translocations. These results indicate that cells with translocations can arise in mouse f-HSCs but exist at a lower frequency than in the mothers 24 h after X-ray exposure. Thus, it seems likely that translocation-bearing f-HSCs are generated but subsequently disappear, so that the frequency of lymphocyte translocations may decrease and reach the control level by the time the animals reach adulthood.
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