DNA damage, micronucleus formation, and cell death from super(125)I decays in DNA

CHO cells were pulse-labeled with super(125)I-iododeoxyuridine, harvested 30 min or 5 h after labeling, and stored at -196 degree C for accumulation of super(125)I decays. The 30-min groups yielded low-LET survival curves (large shoulder, D sub(0) 136 decays/cell); 5-h groups showed a high-LET pattern of cell killing (no shoulder, D sub(0) 45 decay/cell). Surprisingly, the shift in super(125)I action was abolished in cells exposed to HAT medium; both 30-min and 5-h cell groups exhibited high-LET-type killing (no shoulder, D sub(0) 52 decays/cell). The striking difference in cell death was not accompanied by any change in induction or repair of DNA DSBs, but the pattern of micronucleus formation (and by implication chromosome damage) did parallel super(125)I-induced cell death. These findings suggest that cell killing may not be directly linked to the absolute number of DNA DSBs and that damage to higher-order genome structures may be an important factor in radiation-induced cell death.