DNA double-strand breaks induced by decay of 123I-labeled Hoechst 33342: Role of DNA topology

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

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

Results: Each ¹²³I decay in SC DNA produces a DSB yield of 0.18 ± 0.01. On the basis of DSB yields for ¹²⁵IEH (0.52 ± 0.02 for SC and 1.62 ± 0.07 for L, reported previously) and dosimetric expectations, a DSB yield of ～0.5 (3 × 0.18) per ¹²³I decay is expected for L DNA. However, no DSB are observed for the L form, even after ～2 × 10¹¹ decays of ¹²³I per μg DNA, whereas a similar number of ¹²⁵I decays produces DSB in ～40% of L DNA.

Conclusion: ¹²³IEH-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.