Lethality of heavy ion-induced DNA double-strand breaks in mammalian cells.

Cell killing and the production of DNA double-strand breaks (dsbs) were measured in parallel for V79 cells and a human tumour cell line (Caski) following exposure to radiations of differing linear energy transfer (LET) including accelerated heavy ions. Dsb induction was assessed by neutral filter elution (pH 7.4) and elution from agarose plugs in pulsed-field electrophoresis. The elution data were consistent with linear lesion induction and allowed to derive dsb yields or production cross-sections (sigma dsb), respectively. Both cell lines as well as the two elution approaches gave comparable results. sigma dsb was found to rise up to the heaviest ions used (LET = 11,500 keV/microns) but relative biological effectiveness was always smaller than unity. Slopes of the exponential survival curves (final slope with 60Co-radiation) were normalized to the respective dsb yields and allowed to calculate the relative lethality per induced dsb. This parameter increased with LET up to about 300 keV/microns followed by a steep decline for the very heavy ions. The extent of dsb rejoining was concomitantly reduced with ionization density.