DNA structure change induced by guanosine radicals -- a theoretical and spectroscopic study

Abstract

Proton radiation therapy is one of the newest and most promising methods used in modern oncology. Nonetheless, the dissemination of that method may result challenging. This is partially due to the fact that the mechanism of DNA damage induced by protons, which is one of the ways proton radiation interacts with tissues, has not been fully understood yet. It is well known that ionizing radiation especially ions such as protons may directly damage DNA but it also causes the formation of radicals, which may lead to even more serious damage of the DNA sugar-backbone than direct interaction with charged ion. In this article we focus on the influence of guanine radicals on the DNA structure, namely the conformation and stability of the DNA strand. We present the theoretical results of the optimization calculations of DNA structures with guanine radical-adenine pairs as well as calculated Raman spectra. By combining theoretical calculations with the experimental spectra we were able to explain molecular modifications of the DNA sugar-backbone affected by guanine radicals formed upon radiation exposure, which lead to spectral changes between spectra of control and irradiated DNA. Thus we established a pathway of the formation of DNA damage caused by protons.