Double-strand break yield following 125I decay--effects of DNA conformation.
The decay of iodine-125 (125I) 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 cells, the .OH 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 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 scavenger dimethyl sulfoxide (DMSO) of 125I-induced DNA double-strand breaks (DSB). The data indicate that DMSO cannot protect plasmid DNA against DSB damage from 125I decaying within a few angstroms from DNA. However, DMSO attenuated DSB production in V79 cells following the decay of DNA-incorporated 125I, 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.
Kassis
A I
AI
Department of Radiology, Harvard Medical School, Boston, 02115-5729, USA. amin_kassis@hms.harvard.edu
Walicka
M A
MA
Adelstein
S J
SJ
D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002843:Chromatin / Q000235:genetics* / Q000528:radiation effects*; D006224:Cricetinae; D004247:DNA / Q000737:chemistry* / Q000528:radiation effects*; D004249:DNA Damage / Q000528:radiation effects*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004583:Electrons / Q000009:adverse effects*; D005347:Fibroblasts / Q000528:radiation effects; D007457:Iodine Radioisotopes / Q000009:adverse effects* / Q000493:pharmacokinetics; D008168:Lung / Q000166:cytology; D008962:Models, Theoretical; D009690:Nucleic Acid Conformation; D010957:Plasmids; D011837:Radiation-Protective Agents / Q000494:pharmacology*
D002843:Chromatin; D007457:Iodine Radioisotopes; D011837:Radiation-Protective Agents; D004247:DNA; D004121:Dimethyl Sulfoxide