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Low dose-rate X-irradiation induces larger deletions at the human HPRT locus than high dose-rate X-irradiation. 1997

N Colussi, and P H Lohman
Department of Radiation Genetics and Chemical Mutagenesis (MGC), Leiden University, The Netherlands.

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.

UI MeSH Term Description Entries
D007041 Hypoxanthine Phosphoribosyltransferase An enzyme that catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate and hypoxanthine, guanine, or MERCAPTOPURINE to the corresponding 5'-mononucleotides and pyrophosphate. The enzyme is important in purine biosynthesis as well as central nervous system functions. Complete lack of enzyme activity is associated with the LESCH-NYHAN SYNDROME, while partial deficiency results in overproduction of uric acid. EC 2.4.2.8. Guanine Phosphoribosyltransferase,HPRT,Hypoxanthine-Guanine Phosphoribosyltransferase,IMP Pyrophosphorylase,HGPRT,HPRTase,Hypoxanthine Guanine Phosphoribosyltransferase,Phosphoribosyltransferase, Guanine,Phosphoribosyltransferase, Hypoxanthine,Phosphoribosyltransferase, Hypoxanthine-Guanine,Pyrophosphorylase, IMP
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004307 Dose-Response Relationship, Radiation The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation. Dose Response Relationship, Radiation,Dose-Response Relationships, Radiation,Radiation Dose-Response Relationship,Radiation Dose-Response Relationships,Relationship, Radiation Dose-Response,Relationships, Radiation Dose-Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014965 X-Rays Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard X-rays are the higher energy, shorter wavelength X-rays. Soft x-rays or Grenz rays are less energetic and longer in wavelength. The short wavelength end of the X-ray spectrum overlaps the GAMMA RAYS wavelength range. The distinction between gamma rays and X-rays is based on their radiation source. Grenz Ray,Grenz Rays,Roentgen Ray,Roentgen Rays,X Ray,X-Ray,Xray,Radiation, X,X-Radiation,Xrays,Ray, Grenz,Ray, Roentgen,Ray, X,Rays, Grenz,Rays, Roentgen,Rays, X,X Radiation,X Rays,X-Radiations
D017353 Gene Deletion A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. Deletion, Gene,Deletions, Gene,Gene Deletions

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