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

Abstract

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.