Dna Strand Breakage by¹²⁵I-Decay in A Synthetic Oligodeoxynucleotide: Fragment distribution and evaluation of DMSO protection effect

Abstract

A double stranded oligodeoxynucleotide containing a single 125I-dC in a defined location was used to investigate DNA strand breakage resulting from 125I decay. Samples of a 41 bp oligodeoxynucleotide were incubated in 20 mM phosphate buffer (PB), or PB plus 2 M dimethylsulphoxide (DMSO), at 4 degrees C during 18-20 days. The 32P-5'-end labelled DNA fragments produced by 125I decays were separated on denaturing polyacrylamide gels, and the 32P activity in each fragment was determined by scintillation counting after elution of fragments from gel. Most of the breaks, around 90%, occurred within 4-5 nucleotides of the 125I-dC, but DNA breaks were detected up to 16 nucleotides from the decay site. The 125I-dC was located at the 21st nucleotide from the 32P-5'-end label, and since 32P was not detected in fragments longer than 20 nucleotides, it was assumed that all 125I decay events produce at least one break in the 125I-labelled DNA strand. The results show a considerable protection effect of DMSO on DNA breaks at sites >5-6 nucleotides from the 125I location. The probability of breaks in this region was decreased with DMSO by a factor of 2 to 8-fold, suggesting significant role for radical-mediated DNA breaks at the more distant sites. However, the total protection effect of DMSO is rather small: 1.1, because of the small contribution of breakage at distant sites to the total yield.

Quantitative modelling of DNA damage using Monte Carlo track structure method

“…These include average energy loss, ionisation energy, oscillator strength and average excitation potential ranging from 12 to about 30 eV. To obtain a more realistic value based on experimental data [11,[31][32][33], experiments were simulated in which the DNA fragment length distributions were measured after decay of incorporated 125 I [34,35]. These calculations provided an experimentally based average value of 17.5 eV in the sugar-phosphate moiety, based on best agreement between empirical fitting of the experimental 34 [33] expt.…”

Protection by DMSO against Cell Death Caused by Intracellularly Localized Iodine-125, Iodine-131 and Polonium-210

“…In addition to the mammalian cell experiments described above, other studies have been carried out with plasmids and oligonucleotides in an effort to elucidate the mechanisms by which Auger electron emitters impart biological damage in DNA (14)(15)(16)(17)(18). These studies have uniformly implicated direct effects as the primary mechanism involved in the damage suffered by naked DNA.…”

Radiation Protection by Cysteamine against the Lethal Effects of Intracellularly Localized Auger Electron, a- and ß-Particle Emitting Radionuclides

“…The DMF values shown in Table 1 (17), which led us to suggest that a portion of the lethal damage caused by radionuclides incorporated into the DNA of mammalian cells may be due to direct effects, a premise supported by other data sets (29,30). These data suggest that direct effects from 125 I decays in the DNA may be responsible for DNA damage within a few base pairs of the decay site; however, the consequence of this damage appears to be small relative to the overall damage responsible for cell death (7,12,16,17).…”