DNA sequence-dependent damage by Auger electrons in fibroblast cell: a geant4-DNA study
摘要
This research investigated the effects of DNA sequence on the single strand breaks (SSBs) and double strand breaks (DSBs) of DNA induced by Auger electron-emitting radionuclides in an atomic model of fibroblast cells using the Geant4-DNA toolkit. For this, two cells (C1 and C2) and their nuclei (N1 and N2), defined as homogeneous ellipsoids of liquid water of unit density, were considered. An atomic DNA model constructed in the Geant4-DNA toolkit was placed inside N1 and N2. While N1 solely consisted of Cytosine-Guanine (C-G) sequences, N2 contained a novel DNA sequence (damage-specific DNA-binding protein 2 (DDB2)), which has not been investigated to date. This sequence includes nucleotide motifs such as C-G, Adenine-Thymine (A-T), Guanine-Cytosine (G-C), and Thymine-Adenine (T-A). The total numbers of direct and indirect SSBs, DSBs, and hybrid DSBs (HDSBs), caused by five widely-used Auger electron-emitting radionuclides, including 99mTc, 111In, 123I, 125I, and 201Tl were quantified at the cellular level. The results show that the total DNA damage, from greatest to least, corresponds to 201Tl, 125I, 123I, 111In, and 99mTc. In addition, incorporating DDB2 base pairs (bp) into the DNA sequences increased the DNA damage by approximately 31% compared to the case with only C–G bp. The findings of the present study indicate that 201Tl and 125I, due to their higher decay yields of sub-1 keV electron emissions (enabling highly localized energy deposition within the DNA strands), are more effective candidates for inducing DNA strand breaks in a single tumour cell compared to 123I, 111In, and 99mTc.