Speaker
Description
About 80% of the energy absorbed in cells exposed to high-energy ionizing radiation (IR), produces firstly ions and secondary electrons. These latter posse the largest portion of the deposited energy (E), with an initial energy distribution lying essentially below 30 eV and peaking around 9-10 eV. Although some low-energy (E<20 eV) electrons (LEEs) can further ionize biological tissues, they mostly interact with biomolecules via the formation of a transient anions (TAs). TAs have lifetimes varying from one femtosecond to several picoseconds and can efficiently break chemical bonds by dissociative electron attachment (DEA), or by autoionization, when the target molecule is left in a dissociative excited state. In large biomolecules, such as DNA, TAs are formed on fundamental constituents (e.g., a base or phosphate group) [1].
In this talk, the results from LEE impact on plasmid DNA will be presented and the mechanisms leading to various lesions under single collision conditions will be explained. Plasmids constitute the form of DNA found in mitochondria and appear as a suitable model of genomic DNA. The plasmids were condensed on Ta substrates, and thereafter transferred to vacuum to be irradiated. The samples recuperated from vacuum were analyzed by electrophoresis and enzyme treatment to quantitate the yields of single and double strand breaks, other cluster damages, isolated base lesions, and crosslinks. From the electron-energy dependence of the damage yields, it was generally concluded that the decay of TAs into destructive channels played a major role in inducing these lesions in the 0-20 eV energy range [2].
Describing the role of LEEs in damaging the type of DNA found in living organisms has implications not only in conventional radiotherapy, but in more recent treatment modalities, such as targeted radionuclide therapy, nanoparticle-aided radiotherapy and heavy-ion radiotherapy. Examples will be provided at the conference, to illustrate the specific role of LEEs in the development of these new radiotherapeutic modalities, which produce large, localized densities of short-range LEEs, resulting in a reduction of radiation damage to healthy tissues for a given absorbed dose by cancer cells [3]. Moreover, it will be shown that chemotherapeutic drugs can amplify LEE-induced damage. Consequently, fundamental knowledge of LEE-interactions with DNA bound to such drugs should lead to improve treatments in concomitant chemoradiation therapy.
REFERENCES
[1] Y. Gao, Y. Zheng, L. Sanche, International Journal of Molecular Science 22, 7879 (2021).
[2] Y. Dong, Y. Gao, W. Liu, T. Gao, Y. Zheng, L. Sanche, Journal of Physical Chemistry Letters 10, 2985-2990 (2019).
[3] M. Khosravifarsani, S. Ait-Mohand, B. Paquette, L. Sanche and B. Guérin, Journal of Medical Chemistry 64, 6765-6776 (2021).