LOW-LET AND HIGH-LET RADIATION ACTION OF I-125 DECAYS IN DNA - EFFECTOF CYSTEAMINE ON MICRONUCLEUS FORMATION AND CELL-KILLING

Chinese hamster ovary cells were pulse-labeled with I-125-iododeoxyuri dine during early S phase, and cell samples were harvested 30 min or 5 h after labeling. The samples were frozen (with or without 25 mill cy steamine) and stored at -196 degrees C for accumulation of I-125 decay s. X-ray control experiments were performed at 37 degrees C and -196 d egrees C. Aliquots of cells were plated for evaluating micronucleus fo rmation and cell survival. The results demonstrated a striking shift i n micronucleus formation and cell death with time after labeling. Cell s frozen 30 min after labeling exhibited effects typical of low-LET ra diation, but cells frozen 5 h after labeling showed a response charact eristic of high-LET radiation. Cysteamine provided protection against the effects of I-125 during the initial phase of effects characteristi c of low-LET radiation, but no protection was seen during the phase ch aracteristic of high-LET radiation. When cell survival was evaluated a s a function of micronucleus frequency rather than dose in decays/cell , the survival curves for all treatment groups became superimposed. Pr evious work using the same experimental system had failed to show a di rect link between I-125-induced DNA double-strand breaks and cell deat h. These findings are consistent with the hypothesis that DNA damage m ay not be the sole mechanism for cell killing and that damage to highe r-order structures in the cell nucleus may contribute to (or modify) r adiation-induced cell death. (C) 1995 by Radiation Research Society