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电离辐射后抗辐射和辐射敏感小鼠心脏中XRCC1基因的转录情况。

The transcription of the XRCC1 gene in the heart of radiation-resistant and radiation-sensitive mice after ionizing irradiation.

作者信息

Labudova O, Hardmeier R, Rink H, Lubec G

机构信息

University of Vienna, Department of Pediatrics, Vienna, Austria.

出版信息

Pediatr Res. 1997 Mar;41(3):435-9. doi: 10.1203/00006450-199703000-00022.

Abstract

The XRCC1 (X-Ray Repair Cross Complementing) gene was described to play a role for the sensitivity of mammalian cell lines toward ionizing irradiation. Cells with a mutation of this gene present with decreased single strand break repair and reduced recombination repair, they show increased double strand breaks, and sister chromatid exchange is increased up to 10-fold. The goal of our study was to investigate the transcription of this gene in the heart after ionizing irradiation in the mouse. Furthermore, we intended to examine whether radiation-sensitive mice would show a transcriptional pattern different from radiation-resistant mice. Radiation-sensitive BALB/c/J Him mice and radiation-resistant C3H He/Him mice were whole body irradiated with x-ray at 2, 4, and 6 Gy and killed 5, 15, and 30 min after irradiation. mRNA was isolated from the heart and hybridized with probes for XRCC1 and beta-actin as a housekeeping gene control. Irradiation at 2 Gy showed increased transcription of XRCC1 at 5 min in the C3H He/Him group, approached XRCC1 transcription of BALB/c J/Him mice at 15 min, and was lower in the latter at 30 min after irradiation. Irradiation at 4 Gy showed double the transcription at 5 min and an about 3-fold rapid increase of mRNA XRCC1 in the radiation-resistant group at 15 min after irradiation, returning to the transcriptional level of sensitive animals at 30 min. Irradiation at 6 Gy seemed to overwhelm the system in both groups, but resistant mice still showed higher levels of XRCC1 transcription. We conclude that radiation-resistant mice show a higher transcription level for the XRCC1 gene in the heart early after x-ray whole body irradiation. This findings is the first in vivo study on XRCC1 of this kind and may in part explain the differences in the radiation sensitivity between the two strains studied.

摘要

XRCC1(X射线修复交叉互补)基因被认为在哺乳动物细胞系对电离辐射的敏感性方面发挥作用。该基因突变的细胞单链断裂修复能力下降,重组修复能力降低,双链断裂增加,姐妹染色单体交换增加高达10倍。我们研究的目的是调查小鼠在接受电离辐射后心脏中该基因的转录情况。此外,我们打算检查辐射敏感小鼠是否会表现出与辐射抗性小鼠不同的转录模式。对辐射敏感的BALB/c/J Him小鼠和辐射抗性的C3H He/Him小鼠进行2、4和6 Gy的全身X射线照射,并在照射后5、15和30分钟处死。从心脏中分离mRNA,并与用于XRCC1的探针以及作为管家基因对照的β-肌动蛋白探针杂交。2 Gy照射后,C3H He/Him组在5分钟时XRCC1转录增加,在15分钟时接近BALB/c J/Him小鼠的XRCC1转录水平,照射后30分钟时后者较低。4 Gy照射后,抗性组在5分钟时转录增加一倍,在照射后15分钟时mRNA XRCC1迅速增加约3倍,在30分钟时恢复到敏感动物的转录水平。6 Gy照射似乎使两组的系统不堪重负,但抗性小鼠仍显示出较高水平的XRCC1转录。我们得出结论,辐射抗性小鼠在全身X射线照射后早期心脏中XRCC1基因的转录水平较高。这一发现是此类关于XRCC1的首次体内研究,可能部分解释了所研究的两个品系之间辐射敏感性的差异。

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