Low dose-rate X-irradiation induces larger deletions at the human HPRT locus than high dose-rate X-irradiation

Purpose: To investigate the size of deletions induced by low dose-rate (LDR) X-irradiation in relation to the induction by high dose-rate (HDR) X-irradiation at the HPRT locus of human lymphoblastoid WI-L2-NS cells. Materials and methods: The molecular nature of HPRT deletions in human WI-L2-NS lymphoblasts was investigated after LDR or HDR X-irradiation with a total dose of 4 Gy using a set of nine Xq26 sequence tagged sites (STS loci) markers surrounding the hprt gene and covering approximately 2.75 Mb. Results: Eleven of 24 LDR X-ray-induced mutants contained a deletion of the entire hprt gene, whereas this was the case in 10 of 19 HDR X-irradiation-induced mutants. Most of the LDR and HDR total gene deletions exhibited also loss of markers adjacent to the HPRT locus, 10/11 and 7/10 respectively. The largest HDR X-irradiation induced deletion was 0.89 Mb, while the largest deletion observed after LDR X-irradiation (4/11 HPRT deletion mutants) extended outside the investigated region in both proximal (> 0.57 Mb) and distal directions (> 2 Mb). Conclusions: The average size of HPRT deletions after LDR X-irradiation was significantly larger (p=0.0024) than following HDR, suggesting that an inverse dose-rate effect exists for the size of deletions induced by X-irradiation.