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 fr agment on chromosome 21 of cells of a normal human fibroblast cell lin e. Correct rejoining of DSBs was followed by measuring reconstitution of the original-size NotI fragment, and this was compared to total rej oining 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/mu m, it was found that the repair kinetics was generally slower after irradiation with high-LET particles compare d 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 afte r 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 aberration s, deletion mutations and other biological end points. (C) 1998 by Rad iation Research Society.