Joining of correct and incorrect DNA ends at double-strand breaks produced by high-linear energy transfer radiation in human fibroblasts.
DNA double-strand breaks (DSBs) were measured within a 3.2-Mbp NotI fragment on chromosome 21 of cells of a normal human fibroblast cell line. Correct rejoining of DSBs was followed by measuring reconstitution of the original-size NotI fragment, and this was compared to total rejoining as measured by a conventional pulsed-field gel electrophoresis technique (FAR assay). After 80 Gy of particle irradiations with LETs in the range of 7-150 keV/microm, it was found that the repair kinetics was generally slower after irradiation with high-LET particles compared to X irradiation and that a larger proportion of the breaks remained unrepaired after 24 h. On the other hand, the misrejoining frequency as measured by the difference between correct and total rejoining after 24 h did not change with LET, but was approximately the same for all radiations at this dose, equal to 25-30% of the initial breaks. This result is discussed in relation to formation of chromosomal aberrations, deletion mutations and other biological end points.
Löbrich
M
M
Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley 94720, USA.
Cooper
P K
PK
Rydberg
B
B
D002478:Cells, Cultured; D002869:Chromosome Aberrations; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics / Q000528:radiation effects; D004247:DNA / Q000737:chemistry / Q000378:metabolism* / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D007700:Kinetics; D018499:Linear Energy Transfer; D009693:Nucleic Acid Hybridization; D012062:Relative Biological Effectiveness
D004247:DNA