Transcription of the XRCC1 Gene in Kidneys of Radiosensitive and Radioresistant Mice following Whole-Body Irradiation

Abstract

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 β-actin as a housekeeping gene control. Following irradiation at 2 Gy, radiation-resistant mice increased transcriptional levels of mRNA-XRCC1/mRNA-β-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.