Low dose X-radiation adaptive response in spleen and prostate of Atm knockout heterozygous mice

Low dose X-radiation adaptive response in spleen and prostate of Atm knockout heterozygous mice
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DOI:
10.1080/09553000701420582
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发表时间:
2007-01-01
影响因子:
2.6
通讯作者:
Sykes, Pamela J.
Sykes, Pamela J.
中科院分区:
医学3区
文献类型:
--
作者:
Day, Tanya K.;Hooker, Antony M.;Sykes, Pamela J.

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目的:研究共济失调毛细血管扩张症(Atm)基因敲除突变的杂合子对辐射适应性反应的影响。材料和方法:通过pKZ 1倒位频率测量的DNA重组,在用0.01或10 mGy X-射线引发剂量处理后3天,通过组织化学定量Atm敲除杂合前列腺和脾脏中的结果:0.01mGy单次照射可诱导脾脏和前列腺细胞内的反转频率,10 mGy剂量照射可抑制一定比例的内源性反转。两种剂量均诱导了对随后高激发剂量的适应性反应(幅度相似),导致脾脏和前列腺染色体倒位。适应性反应完全阻止了从1000毫戈瑞的挑战剂量和内源性倒置的比例的诱导倒置。在Atm敲除杂合子前列腺中观察到的适应性反应和跨腺体横截面的倒置分布与先前研究中在Atm野生型前列腺中诱导的那些相似。Atm基因敲除突变的杂合性不影响内源性pKZ 1倒位频率,即对此处使用的单一低辐射剂量的倒位响应,或诱导pKZ 1小鼠脾或前列腺内翻的辐射适应性反应。
Purpose: To investigate the effect of being heterozygous for a knockout mutation in the ataxia telangiectasia (Atm) gene on radiation adaptive response.Materials and methods: DNA recombination, as measured by pKZ1 inversion frequency, was quantified by histochemistry in Atm knockout heterozygous prostate and spleen 3 days after treatment with a priming dose of 0.01 or 10 mGy X-radiation 4 h prior to a challenge dose of 1000 mGy.Results: In spleen and prostate, a single dose of 0.01 mGy caused an induction in inversion frequency but a dose of 10 mGy prevented the induction of a proportion of endogenous inversions. Both doses induced an adaptive response, of similar magnitude, to a subsequent high challenge dose for chromosomal inversions in both spleen and prostate. The adaptive response completely prevented the induction of inversions from a 1000 mGy challenge dose and also a proportion of endogenous inversions. The adaptive responses and distribution of inversions across gland cross-sections observed here in Atm knockout heterozygote prostate were similar to those induced in Atm wild-type prostate in a previous study.Conclusions: Being heterozygous for a knockout mutation in the Atm gene does not affect the endogenous pKZ1 inversion frequency, the inversion response to single low radiation doses used here, or the induction of a radiation adaptive response for inversions in pKZ1 mouse spleen or prostate.