THE NUCLEUS IS THE TARGET FOR RADIATION-INDUCED CHROMOSOMAL INSTABILITY

We have previously described chromosomal instability in cells of a hum an-hamster hybrid cell line after exposure to X rays. Chromosomal inst ability in these cells is characterized by the appearance of novel chr omosomal rearrangements multiple generations after exposure to ionizin g radiation. To identify the cellular target(s) for radiation-induced chromosomal instability, cells were treated with I-125-labeled compoun ds and frozen. Radioactive decays from I-125 cause damage to the cell primarily at the site of their decay, and freezing the cells allows da mage to accumulate in the absence of other cellular processes. We foun d that-the decay of I-125-iododeoxyuridine, which is incorporated into the DNA, caused chromosomal instability. While cell killing and first -division chromosomal rearrangements increased with increasing numbers of I-125 decays, the frequency of chromosomal instability was indepen dent of dose. Chromosomal instability could also be induced from incor poration of I-125-iododeoxyuridine without freezing the cells for accu mulation of decays, This indicates that DNA double-strand breaks in fr ozen cells resulting from 125I decays failed to lead to instability. I ncorporation of an I-125-labeled protein (I-125-succinyl-concanavalin A), which was internalized into the cell and/or bound to the plasma me mbrane, neither caused chromosomal instability nor potentiated chromos omal instability induced by I-125-iododeoxyuridine. These results show that the target for radiation-induced chromosomal instability in thes e cells is the nucleus. (C) 1998 by Radiation Research Society.