Determining How Ions Degrade DNA May Enhance Radiotherapy for Cancer Patients

Icelandic scientists now have a better determination of how short DNA strands decompose in microseconds. They discovered new fragmentation pathways that occur universally when DNA strands are exposed to metal ions from a range of alkaline and alkaline earth elements. These new insights could help optimize tumor therapy through a better determination of how radiation and its by-products, reactive intermediate particles, interact with complex DNA structures.

These ions tend to replace protons in the DNA backbone, and at the same time, trigger a reactive conformation, which leads more readily to fragmentation. Dr. Andreas Piekarczyk, from the University of Iceland (Reykjavík), and colleagues published their findings June 2014 in the European Physical Journal D.

In cancer radiotherapy, it is not the radiation by itself that directly damages the DNA strands, or oligonucleotides. Instead, it is the secondary reactive particles, leading to the creation of charged intermediates. The researchers have examined one of these charged intermediates in the form of so-called protonated metastable DNA hexamers. In so doing, the investigators created selected oligonucleotide-metal-ion complexes that they selected to have between zero and six metal ions. They then tracked these complexes’ fragmentation reactions using time-of-flight mass spectrometry. By comparing the different species, they could deduce how the underlying metal-ion-induced oligonucleotide fragmentation works.

The scientists discovered that metal ion-induced fragmentation of oligonucleotides is universal with all alkaline and alkaline earth metal ions, for example, lithium, Li+; potassium, K+; rubidium, Rb+; magnesium, Mg2+; and calcium, Ca2+. They had earlier arrived at the same conclusion for sodium ions, which are abundant in nature, in the form of sodium chloride. Once the number of sodium ions per nucleotide is high enough, the study revealed, it induces an unanticipated oligonucleotide fragmentation reaction.

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