Molecular hydrogen attenuates radiation-induced nucleobase damage to DNA in aerated aqueous solutions

Abstract

Purpose: The main aim of the present study is to gain mechanistic insights into the modulating effect of molecular hydrogen on the γ-radiation-induced alteration pathways of DNA nucleobases.

Materials and methods: Aerated aqueous solutions of calf thymus DNA were exposed to a ⁶⁰Co source at doses ranging from 0 to 55 Gy under normoxic conditions, in the presence or not of 0.7 MPa hydrogen or helium. The measurement of several modified bases was performed using HPLC associated with electrospray ionization tandem pass spectrometry (HPLC-ESI-MS/MS). Bleaching of aqueous solutions of p-nitrosodimethylaniline (p-NDA) solutions was also used to allow the quantification of hydroxyl radical (•OH) formation.

Results: pNDA bleaching was significantly reduced in the presence of hyperbaric hydrogen. This is undoubtedly due to ^•OH scavenging by H₂ since, under the same conditions, He had no effect. Similarly, base alterations were significantly reduced in the presence of hydrogen, as compared to controls under normal atmosphere or in the presence of helium. The relative proportions of modified nucleobases were not changed, showing that the only effect of H₂ is to scavenge ^•OH without exhibiting reducing properties.

Conclusions: Our findings demonstrate that H₂ exerts a significant protection against radiation-induced DNA base damage in aqueous solutions, ^•OH scavenging being the only mechanism involved.

Keywords:

• DNA base oxidation
• hydroxyl radical scavenging
• molecular hydrogen-mediated protection
• oxidized 2′-deoxyribonucleosides

Acknowledgments

The work was supported by CNRS, Aix Marseille University, CEA and COMEX SA. Hadia Bensalem help us with the experimental work.

Disclosure statement

The authors declare that there is no conflict of interest.