Low-LET and high-LET radiation action of 125I decays in DNA: effect of cysteamine on micronucleus formation and cell killing.
Chinese hamster ovary cells were pulse-labeled with 125I-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 mM cysteamine) and stored at -196 degrees C for accumulation of 125I 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 125I 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 125I-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.
Institute of Molecular Biophysics, Florida State University, Tallahassee 32306.
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Hofer
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Bao
D000818:Animals; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D003543:Cysteamine / Q000494:pharmacology*; D004247:DNA / Q000528:radiation effects*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D007457:Iodine Radioisotopes; D018499:Linear Energy Transfer; D048629:Micronuclei, Chromosome-Defective; D014965:X-Rays
D007457:Iodine Radioisotopes; D003543:Cysteamine; D004247:DNA; D004121:Dimethyl Sulfoxide