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

Chinese hamster ovary cells were pulse-labeled with I-125-iododeoxyuridine 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 cysteamine) and stored at -196 degrees C for accumulation of I-125 decays. X-ray control experiments were performed at 37 degrees C and -196 degrees C. Aliquots of cells were plated for evaluating micronucleus formation and cell survival. The results demonstrated a striking shift in micronucleus formation and cell death with time after labeling. Cells frozen 30 min after labeling exhibited effects typical of low-LET radiation, but cells frozen 5 h after labeling showed a response characteristic of high-LET radiation. Cysteamine provided protection against the effects of I-125 during the initial phase of effects characteristic of low-LET radiation, but no protection was seen during the phase characteristic of high-LET radiation. When cell survival was evaluated as a function of micronucleus frequency rather than dose in decays/cell, the survival curves for all treatment groups became superimposed. Previous work using the same experimental system had failed to show a direct link between I-125-induced DNA double-strand breaks and cell death. These findings are consistent with the hypothesis that DNA damage may not be the sole mechanism for cell killing and that damage to higher-order structures in the cell nucleus may contribute to (or modify) radiation-induced cell death. (C) 1995 by Radiation Research Society