Vacuum-UV induced DNA strand breaks
- Radiation therapy is a basic part of cancer treatment. To increase the DNA damage in carcinogenic cells and preserve healthy tissue at the same time, radiosensitizing molecules such as halogenated nucleobase analogs can be incorporated into the DNA during the cell reproduction cycle. In the present study 8.44 eV photon irradiation induced single strand breaks (SSB) in DNA sequences modified with the radiosensitizer 5-bromouracil (U-5Br) and 8-bromoadenine ((8Br)A) are investigated. U-5Br was incorporated in the 13mer oligonucleotide flanked by different nucleobases. It was demonstrated that the highest SSB cross sections were reached, when cytosine and thymine were adjacent to U-5Br, whereas guanine as a neighboring nucleobase decreases the activity of U-5Br indicating that competing reaction mechanisms are active. This was further investigated with respect to the distance of guanine to U-5Br separated by an increasing number of adenine nucleotides. It was observed that the SSB cross sections were decreasing with an increasing numberRadiation therapy is a basic part of cancer treatment. To increase the DNA damage in carcinogenic cells and preserve healthy tissue at the same time, radiosensitizing molecules such as halogenated nucleobase analogs can be incorporated into the DNA during the cell reproduction cycle. In the present study 8.44 eV photon irradiation induced single strand breaks (SSB) in DNA sequences modified with the radiosensitizer 5-bromouracil (U-5Br) and 8-bromoadenine ((8Br)A) are investigated. U-5Br was incorporated in the 13mer oligonucleotide flanked by different nucleobases. It was demonstrated that the highest SSB cross sections were reached, when cytosine and thymine were adjacent to U-5Br, whereas guanine as a neighboring nucleobase decreases the activity of U-5Br indicating that competing reaction mechanisms are active. This was further investigated with respect to the distance of guanine to U-5Br separated by an increasing number of adenine nucleotides. It was observed that the SSB cross sections were decreasing with an increasing number of adenine spacers between guanine and U-5Br until the SSB cross sections almost reached the level of a non-modified DNA sequence, which demonstrates the high sequence dependence of the sensitizing effect of U-5Br. (8Br)A was incorporated in a 13mer oligonucleotide as well and the strand breaks were quantified upon 8.44 eV photon irradiation in direct comparison to a non-modified DNA sequence of the same composition. No clear enhancement of the SSB yield of the modified in comparison to the non-modified DNA sequence could be observed. Additionally, secondary electrons with a maximum energy of 3.6 eV were generated when using Si as a substrate giving rise to further DNA damage. A clear enhancement in the SSB yield can be ascertained, but to the same degree for both the non-modified DNA sequence and the DNA sequence modified with (8Br)A.…
Author details: | Stefanie VogelORCiDGND, Kenny EbelORCiD, Christian HeckORCiDGND, Robin Mathis SchürmannORCiDGND, Aleksandar R. MilosavljevicORCiD, Alexandre GiulianiORCiD, Ilko BaldORCiDGND |
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DOI: | https://doi.org/10.1039/c8cp06813e |
ISSN: | 1463-9076 |
ISSN: | 1463-9084 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/30633275 |
Title of parent work (English): | Physical chemistry, chemical physics : a journal of European Chemical Societies |
Subtitle (English): | influence of the radiosensitizers 5-bromouracil and 8-bromoadenine |
Publisher: | Royal Society of Chemistry |
Place of publishing: | Cambridge |
Publication type: | Article |
Language: | English |
Date of first publication: | 2019/01/02 |
Publication year: | 2019 |
Release date: | 2021/04/19 |
Volume: | 21 |
Issue: | 4 |
Number of pages: | 8 |
First page: | 1972 |
Last Page: | 1979 |
Funding institution: | German Research Foundation (DFG)German Research Foundation (DFG) [281049597]; Federal Institute for Materials Research and Testing (BAM); DFGGerman Research Foundation (DFG) [GSC 1013]; synchrotron facility SOLEIL [20151010, 99170068] |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Chemie |
DDC classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
Peer review: | Referiert |