Labudova O, Hardmeier R, Kitzmüller E, Rink H, Lubec G
Department of Pediatrics, University of Vienna, Austria.
Nephron. 1998;79(1):61-6. doi: 10.1159/000044993.
The XRCC1 gene was described to play a role in the sensitivity of mammalian cell lines towards ionizing irradiation. Cells with a mutation of this gene present with decreased single-strand break repair and reduced recombination repair, show increased double-strand breaks, and the sister chromatid exchange is increased up to tenfold. The goal of our study was to investigate the transcription of this gene in the kidney following ionizing irradiation in the mouse, as this could be relevant to the pathogenetic mechanisms found in radiation nephropathy. 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 sacrificed 5, 15, and 30 min after irradiation. mRNA was isolated from kidney cortex and hybridized with probes for XRCC1 and beta-actin as a housekeeping gene control. Following irradiation at 2 Gy, radiation-resistant mice increased transcriptional levels of mRNA-XRCC1/mRNA-beta-actin as early as after 5 min, and 15 and 30 min after irradiation, XRCC1 transcription was still higher than in radiation-sensitive mice. At higher radiation doses, no differences were found. This finding 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.
XRCC1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。该基因突变的细胞表现为单链断裂修复能力下降和重组修复减少,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肾脏中该基因的转录情况,因为这可能与放射性肾病的发病机制相关。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小鼠进行全身X射线照射,剂量分别为2、4和6 Gy,并在照射后5、15和30分钟处死。从肾皮质分离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。在2 Gy照射后,辐射抗性小鼠在照射后5分钟时mRNA-XRCC1/mRNA-β-肌动蛋白的转录水平就开始升高,并且在照射后15分钟和30分钟时,XRCC1的转录水平仍高于辐射敏感小鼠。在更高的辐射剂量下,未发现差异。这一发现是关于XRCC1的此类首次体内研究,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。