DOUBLE-STRAND BREAKS FROM I-125 INCORPORATED IN THE DNA AND CELL-DEATH

Track structure calculations of the local energy deposition by electro ns emitted during the decay of I-125 are used to demonstrate that the range of high energy deposition is small (< 10 nm) and restricted to t he DNA and its immediate environment. An experiment in which I-125 is incorporated into the DNA of synchronized CHO cells during a pulse and decays are allowed to accumulate a given time after the incorporation is described. Here it is shown that damage from I-125 decays in newly replicated DNA (cells frozen for decay accumulation within Ih after l abelling) are relatively non-toxic whereas decays in mature DNA (cells frozen 5h after labelling) are highly lethal. It is suggested that du ring DNA maturation the labelled DNA becomes associated with (or reorg anized into) a radiosensitive nuclear structure and that damage to thi s structure is the primary cause of radiation-induced cell death.