The effect of hypoxia on the induction of strand breaks in plasmid DNA by alpha-, beta- and Auger electron-emitters 223Ra, 188Re, 99mTc and DNA-binding 99mTc-labeled pyrene

Abstract

Introduction: Radiation-induced DNA damage occurs from direct and indirect effects. The induction is influenced by the physical characteristics of the radionuclide, especially its linear energy transfer. Hypoxia reduces the effect of irradiation treatment in tumor cells and leads to poor patient outcomes. High linear energy transfer emitters can overcome this obstacle. Our aim is to demonstrate the influence of hypoxia on the interaction of different radiation qualities with isolated DNA.

Methods: PuC19 Plasmid DNA was irradiated with ²²³Ra, ¹⁸⁸Re, ^99mTc and ^99mTc-labeled pyrene with and without DMSO under hypoxia or normoxic conditions. DNA damages in form of single-(SSB) and double-strand breaks (DSB) were analyzed by gel electrophoresis.

Results: Radiation doses up to 200 Gy of ²²³Ra, ¹⁸⁸Re and ^99mTc led to maximal yields of 80% SSB and 30%, 28% and 32% DSB, respectively. Hypoxia had minor effects on damages from ²²³Ra, but caused a small enhancement in DSB for ¹⁸⁸Re and ^99mTc. DMSO prevented DSB completely and reduced SSB from the "free" radionuclides to comparable levels. DNA-binding ^99mTc-labeled pyrene induced less SSB and DSB compared to [^99mTc]TcO₄^-. However, the incubation with DMSO could prevent the SSB and DSB induction only to a minor extent.

Conclusions: Hypoxia does not limit DNA damage induced by ²²³Ra, ¹⁸⁸Re, ^99mTc and ^99mTc-labeled pyrene. Dose-dependent radiation effects were comparable for alpha-emitters and both high- and low-energy electron emitters. The radioprotection by DMSO was not influenced by hypoxia. The results indicate the contribution of mainly indirect radiation effects for ^99mTc, ¹⁸⁸Re and ²²³Ra. ^99mTc-labeled pyrene caused direct DNA damages and Auger-electrons from ^99mTc-labeled pyrene are more effective than high-energy electrons or alpha particles.

Advances in knowledge: Without the consideration of DNA repair mechanisms, oxygen has no direct influence in radiation-induced DNA damages by different radiation qualities.

Implications for patient care: The short-time stimulation with oxygen during patient radiation could have minor influence compared to constant oxygen flooding to overcome hypoxic barriers.

Keywords: Auger-electrons; DMSO; Hypoxia; Plasmid DNA; α-Emitter; β-Emitter.