DNA-DAMAGE, MICRONUCLEUS FORMATION, AND CELL-DEATH FROM I-125 DECAYS IN DNA

CHO cells were pulse-labeled with I-125-iododeoxyuridine, harvested 30 min or 5 h after labeling, and stored at -196 degrees C for accumulat ion of I-125 decays, The 30- min groups yielded low-LET survival curve s (large shoulder, D-0 136 decays/cell); 5-h groups showed a high-LET pattern of cell killing (no shoulder, D-0 45 decay/cell). Surprisingly , the shift in I-125 action was abolished in cells exposed to HAT medi um; both 30-min and 5-h cell groups exhibited high-LET-type killing (n o shoulder, D-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 chromos ome damage) did parallel I-125-induced cell death. These findings sugg est that cell killing may not be directly linked to the absolute numbe r of DNA DSBs and that damage to higher-order genome structures may be an important factor in radiation-induced cell death.