Role of Transient Anions in Chemoradiation Therapy: Base Modifications, Crosslinks and Cluster Damages Induced to Cisplatin-DNA Complexes by 1-20 eV Electrons.

The molecular mechanism of platinum-based drugs in concomitant chemoradiation therapy relies on enhancement of DNA damage in cancer cells, particularly that of detrimental clustered lesions and cross-links induced by the abundant low-energy electrons (LEEs) generated by ionizing radiation. We provide the complete 1-20 eV electron-energy dependence of the yields of all conformational LEE-induced lesions to biological DNA, when it binds to five molecules of the chemotherapeutic drug cisplatin. Recording at 1 eV intervals clearly show that the enhancement of all lesions is particularly intense at the energies of coreexcited transient molecular anions (i.e., TMAs at 5, 6, and 10 eV). New TMAs are observed at 14 and 18 eV, only in yield functions of cisplatin-DNA complexes. Enhancements of all lesions by cisplatin are quantified over the 1-20 eV range, where maxima appear at 14 and 18 eV. The most detrimental lesions to cell survival exhibit the highest enhancements by factors of 2-3. Whereas no cluster lesions are induced by electrons of energy <5 eV in DNA, LEEs of any energy cause clustered damages in the complex. These results confirm the current notion that LEEs and TMAs play a dominant role in the molecular mechanism of platinum-drug chemoradiation therapy.