Sensitizing DNA Towards Low-Energy Electrons with 2-Fluoroadenine.

Abstract

2-Fluoroadenine ((2F) A) is a therapeutic agent, which is suggested for application in cancer radiotherapy. The molecular mechanism of DNA radiation damage can be ascribed to a significant extent to the action of low-energy (<20 eV) electrons (LEEs), which damage DNA by dissociative electron attachment. LEE induced reactions in (2F) A are characterized both isolated in the gas phase and in the condensed phase when it is incorporated into DNA. Information about negative ion resonances and anion-mediated fragmentation reactions is combined with an absolute quantification of DNA strand breaks in (2F) A-containing oligonucleotides upon irradiation with LEEs. The incorporation of (2F) A into DNA results in an enhanced strand breakage. The strand-break cross sections are clearly energy dependent, whereas the strand-break enhancements by (2F) A at 5.5, 10, and 15 eV are very similar. Thus, (2F) A can be considered an effective radiosensitizer operative at a wide range of electron energies.