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


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.
Colussi
N
N
Department of Radiation Genetics and Chemical Mutagenesis (MGC), Leiden University, The Netherlands.
Lohman
P H
PH
D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D017353:Gene Deletion; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D009154:Mutation; D014965:X-Rays
D007041:Hypoxanthine Phosphoribosyltransferase