THE TRANSCRIPTION OF THE XRCC1 GENE IN THE HEART OF RADIATION-RESISTANT AND RADIATION-SENSITIVE MICE AFTER IONIZING IRRADIATION

The XRCC1 (X-Ray Repair Cross Complementing) gene was described to pla y a role for the sensitivity of mammalian cell Lines toward ionizing i rradiation. 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 incr eased up to 10-fold. The goal of our study was to investigate the tran scription 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-re sistant mice. Radiation-sensitive BALB/c/J Him mice and radiation-resi stant C3H He/Him mice were whole body irradiated with x-ray at 2, 4, a nd 6 Gy and killed 5, 15, and 30 min after irradiation, mRNA was isola ted 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 XR CC1 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 af 15 min after irradiation, r eturning 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 lev el for the XRCC1 gene in the heart early after x-ray whole body irradi ation. This finding is the first in vivo study on XRCC1 of this kind a nd may in part explain the differences in the radiation sensitivity be tween the two strains studied.