DNA double-strand breaks induced by decay of (123)I-labeled Hoechst 33342: role of DNA topology.
OBJECTIVE
To determine double-strand-break (DSB) yields produced by decay of minor-groove-bound (123)I-labeled Hoechst 33342 ((123)IEH) in supercoiled (SC) and linear (L) forms of pUC19 DNA, to compare strand-break efficiency of (123)IEH with that of (125)IEH, and to examine the role of DNA topology in DSB induction by these Auger electron emitters.


METHODS
Tritium-labeled SC and L pUC19 DNA were incubated with (123)IEH (0-10.9 MBq) at 4 degrees C. After (123)I had completely decayed (10 days), samples were analyzed on agarose gel, and single-strand-break (SSB) and DSB yields were measured.


RESULTS
Each (123)I decay in SC DNA produces a DSB yield of 0.18 +/- 0.01. On the basis of DSB yields for (125)IEH (0.52 +/- 0.02 for SC and 1.62 +/- 0.07 for L, reported previously) and dosimetric expectations, a DSB yield of approximately 0.5 (3 x 0.18) per (123)I decay is expected for L DNA. However, no DSB are observed for the L form, even after approximately 2 x 10(11) decays of (123)I per microg DNA, whereas a similar number of (125)I decays produces DSB in approximately 40% of L DNA.


CONCLUSIONS
(123)IEH-induced DSB yield for SC but not L DNA is consistent with the dosimetric expectations for Auger electron emitters. These studies highlight the role of DNA topology in DSB production by Auger emitters and underscore the failure of current theoretical dosimetric methods per se to predict the magnitude of DSB.
Balagurumoorthy
Pichumani
P
Department of Radiology, Harvard Medical School, Boston, MA, USA. pbalagurumoorthy@hms.harvard.edu
Wang
Ketai
K
Adelstein
S James
SJ
Kassis
Amin I
AI
D001562:Benzimidazoles; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D053904:DNA Breaks, Single-Stranded / Q000528:radiation effects*; D004278:DNA, Superhelical / Q000528:radiation effects*; D004583:Electrons; D007457:Iodine Radioisotopes / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D010957:Plasmids; D011851:Radioactivity
D001562:Benzimidazoles; D004278:DNA, Superhelical; D007457:Iodine Radioisotopes; C017807:bisbenzimide ethoxide trihydrochloride