Double-strand break yield following I-125 decay - Effects of DNA conformation

The decay of iodine-125 (I-125) is accompanied by the emission of low-energy electrons that dissipate most of their energy in approximately 10 nm from the decay site. In mammalian dells, the (OH)-O-. generated by these electrons are also confined to a small volume. Iodine-125 is thus an excellent probe for assessing the radiobiologic effects produced by (OH)-O-. in close proximity to the site of a decaying atom. We have compared in pUC19 plasmids (naked DNA) and in Chinese hamster V79 lung fibroblasts (chromatin) the modulation by the (OH)-O-. scavenger dimethyl sulfoxide (DMSO) of I-125-induced DNA double-strand breaks (DSB). The data indicate that DMSO cannot protect plasmid DNA against DSB damage from I-125 decaying within a few angstroms from DNA. However, DMSO attenuated DSB production in V79 cells following the decay of DNA-incorporated I-125, thus suggesting that chromatin structure fosters some DSB formation by indirect mechanism(s). DSB production depends on the environment and/or conformation of DNA. Consequently, current biophysical modeling of DNA damage that is based on naked and non-compacted DNA is inadequate for explaining radiobiologic effects at the cellular level.