Strand breaks after the decay of iodine-125 in proximity to plasmid pBR322 DNA.
To elucidate the kinetics of DNA strand breaks caused by low-energy Auger electron emitters in proximity to DNA molecules, we synthesized (125)I-labeled 2-iodoacridine (2-(125)IA), which intercalates with DNA, and 4-iodoacridine (4-(125)IA), which does not. Supercoiled DNA from pBR322 plasmid, labeled with 3H, was purified and incubated with 2-(125)IA or 4-(125)IA in aqueous solution. Reaction mixtures were stored at 4 degrees C to accumulate radiation dose from the decay of (125)I, and DNA was resolved by gel electrophoresis into supercoiled (DNA-I), nicked-circular (DNA-II) and linear (DNA-III) forms, representing undamaged DNA, single-strand breaks (SSBs) and double-strand breaks (DSBs), respectively. Gamma irradiation from an external (137)Cs source led to an exponential decrease in DNA-I with a D0 value of 10.8 +/- 0.3 Gy. Under identical conditions, the D0 values for 2-(125)IA and 4-(125)IA were 22.4 +/- 0.6 x 10(11) disintegrations and 4.7 +/- 0.4 x 10(11) disintegrations, respectively. External gamma irradiation and 4-(125)IA produced SSB/DSB ratios of 26.5 +/- 2.1 and 15.9 +/- 2, respectively, while that for 2-(125)IA was 0.6. The average number of DSBs from each decay of (125)I was 0.67 for 2-(125)IA and 0.27 for 4-(125)IA. The results indicate that the decay of (125)I bound to a DNA-intercalating compound produces DSBs 2.5-fold more efficiently than (125)I bound to a nonintercalating compound and support the theoretical expectations that predict a DSB yield that is highly dependent on the proximity of the Auger electron emitter to DNA.
Sahu
S K
SK
Department of Radiology (Nuclear Medicine), Harvard Medical School, Boston, Massachusetts 02115, USA.
Kortylewicz
Z P
ZP
Baranowska-Kortylewicz
J
J
Taube
R A
RA
Adelstein
S J
SJ
Kassis
A I
AI
D000166:Acridines / Q000494:pharmacology; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D004926:Escherichia coli; D007364:Intercalating Agents / Q000138:chemical synthesis; D007457:Iodine Radioisotopes; D007553:Isotope Labeling / Q000379:methods; D007700:Kinetics; D010957:Plasmids / Q000737:chemistry / Q000528:radiation effects*
C105258:2-iodoacridine; C105259:4-iodoacridine; D000166:Acridines; D007364:Intercalating Agents; D007457:Iodine Radioisotopes; D004247:DNA