Base Release and Modification in Solid-Phase DNA Exposed to Low-Energy Electrons.

Area of Science:

• Radiation chemistry
• Molecular biology
• Biophysics

Background:

• Ionization produces low-energy electrons (LEEs) that can induce DNA damage via dissociative electron attachment (DEA).
• Understanding LEE-induced DNA damage is crucial for radiation biology and safety.

Purpose of the Study:

• To investigate the impact of LEEs on dry DNA damage.
• To compare DNA damage induced by X-rays alone versus X-rays combined with LEEs.
• To quantify DNA base release and modifications.

Main Methods:

• Irradiation of dry DNA (calf-thymus and synthetic oligonucleotides) on glass or tantalum (Ta) substrates using 1.5 keV X-rays.
• Generation of LEEs (average energy 5.8 eV) from the Ta substrate.
• Analysis of non-modified DNA base release and base modifications using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with isotopic dilution.

Main Results:

• DNA deposited on a Ta substrate (emitting LEEs) showed a 20-30% increase in non-modified base release and base modifications compared to DNA on a glass substrate.
• The order of base release was Guanine > Adenine > Thymine ≈ Cytosine, consistent with theoretical predictions of sugar-phosphate cleavage.
• Main LEE-induced base modifications included 5,6-dihydrothymine, 5,6-dihydrouracil, 5-hydroxymethyluracil, and 5-formyluracil.

Conclusions:

• LEEs significantly enhance X-ray-induced DNA damage, primarily through DEA.
• The observed base release suggests initial cleavage of DNA backbone bonds.
• LEE-induced base modifications result from DEA and secondary reactions involving generated atoms and anions.