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Vacuum-UV induced DNA strand breaks - influence of the radiosensitizers 5-bromouracil and 8-bromoadenine

Abstract : 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 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.
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Submitted on : Tuesday, May 26, 2020 - 5:54:37 AM
Last modification on : Wednesday, November 17, 2021 - 2:28:24 PM

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Stefanie Vogel, Kenny Ebel, Christian Heck, Robin M. Schuermann, Aleksandar R. Milosavljević, et al.. Vacuum-UV induced DNA strand breaks - influence of the radiosensitizers 5-bromouracil and 8-bromoadenine. Physical Chemistry Chemical Physics, Royal Society of Chemistry, 2019, 21 (4), pp.1972-1979. ⟨10.1039/c8cp06813e⟩. ⟨hal-02622516⟩

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