Molecular mechanisms underlying radiotherapy

Nucleic acids found in Earth’s living organisms are permanently exposed to ionizing radiation and these interactions are known for their disruptive effects on life. As a consequence, radiation action upon DNA has not only fundamentally influenced the evolution of life on Earth but also is an important contributor to the development of cancer. On the other hand, radiation is commonly used for controlled cell killing in radiotherapy. The molecular response of DNA to ionizing radiation depends sensitively on the interaction site, molecular conformation, and chemical environment and we are able to address these parameters experimentally. Based on the information about individual damage mechanisms we can directly compare with quantum-chemical calculations. We have for instance shown recently that both X-ray and MeV ion impact on DNA leads to emission of more secondary electrons than previously thought, with fundamental consequences for biological radiation damage. We have also shown that ultrafast hydrogen transfer processes are a key part of the damage process.

Multiple valence electron detachment following Auger decay of inner-shell vacancies in gas-phase DN, W. Li, O. Kavatsyuk, W. Douma, X. Wang, R. Hoekstra, D. Mayer, M. Robinson, M. Gühr, M. Lalande, M. Abdelmouleh, M. Ryszka, J.C. Poully, T. Schlathölter, Chem. Sci., 12, 3177, 2021

Intramolecular hydrogen transfer in DNA induced by site-selected resonant core excitation, X. Wang, S. Rathnachalam, K. Bijlsma, W. Li, R. Hoekstra, M. Kubin, M. Timm, B. von Issendorf, V. Zamudio-Bayer, J. T. Lau, S. Faraji, T. Schlathölter, PCCP 24, 11900, 2022

MS-RADAM “ Multiscale Phenomena in Radiation Damage“, MSCA Doctoral Training Network 2025-2029. https://cordis.europa.eu/project/id/101225527