Paradoxical Effects of Iodine-125 Decays in Parent and Daughter DNA: A New Target Model for Radiation Damage

Hofer, K. G., Lin, X. and Schneiderman, M. H. Paradoxical Effects of Iodine-125 Decays in Parent and Daughter DNA: A New Target Model for Radiation Damage. Chinese hamster ovary cells were synchronized at the G1/S-phase boundary of the cell cycle and were pulse-labeled with 125I-iododeoxyuridine 30 min after they entered the S phase. Cell samples were harvested and frozen for accumulation of 125I decays during the first and second G2 phase after labeling. Cell aliquots that had accumulated the desired number of decays were thawed and plated for evaluation micronucleus formation and cell death. Cells subjected to 125I decays during the first G2 phase after labeling exhibited single-hit kinetics of cell killing (n = 1, D0 41 decays/cell). In contrast, decays accumulated during the second G2 phase killed cells with dual-hit kinetics (n = 1.9, D0 81 decays/cell). A similar divergence in the action of 125I was noted for micronucleus formation. These findings indicate that the effects of 125I varied depending on whether the decays occurred in daughter DNA (first G2 phase) or parent DNA (second G2 phase). Control studies with external X rays showed no such divergence of the action of radiation. To account for this paradox, a model is proposed that invokes higher-order chromatin structures as radiation targets. This model implies differential spatial arrangements for parent and daughter DNA in the genome, with DNA strands organized such that a single 125I decay originating in daughter DNA damages two targets during the first G2 phase, but identical decays occurring during the second G2 phase damage only one of the targets.