Double-strand Breaks from 125I Incorporated in the DNA and Cell Death

Track structure calculations of the local energy deposition by electrons emitted during the decay of 125I are used to demonstrate that the range of high energy deposition is small (< 10 nm) and restricted to the DNA and its immediate environment. An experiment in which 125I 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 125I decays in newly replicated DNA (cells frozen for decay accumulation within 1 h after labelling) are relatively non-toxic whereas decays in mature DNA (cells frozen 5 h after labelling) are highly lethal. It is suggested that during DNA maturation the labelled DNA becomes associated with (or reorganized into) a radiosensitive nuclear structure and that damage to this structure is the primary cause of radiation-induced cell death.