REVIEW article
Front. Mol. Biosci.
Sec. Cellular Biochemistry
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1636255
This article is part of the Research TopicIn Honor of Dr. Bruce Ames: Innovations in Mutagenesis and DNA RepairView all articles
Pioneering contribution of Professor Bruce Ames to early development in biochemical aspects of oxidatively generated damage to DNA
Provisionally accepted
- Université de Sherbrooke, Sherbrooke, Canada
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The first part of the memorial review article is devoted to a retrospective of selected topics that were the subject of pioneering studies over the period 1985-2025 by Professor Bruce Ames. Major efforts were made to develop accurate and sensitive assays including HPLC coupled with electrochemical detection for monitoring the formation of 8-oxo-7,8-dihydroguanine in isolated cells and animal tissues. Special attention was provided to the minimization of artefactual oxidation of DNA that occurs during sample preparation. Complementary information on the biological relevance of 8-oxo-7,8-dihydroguanine and 5,6-dihydroxy-5,6-dihydrothymine was gained from the non-invasive measurement of the oxidized bases and nucleosides various mammalian fluids. The second part of the article focuses on the current situation concerning the formation of oxidized bases in cellular DNA produced under various conditions of oxidative stress and enzymatic ten-eleven TEToxidation of 5-methylcytosine. The analysis of DNA base modifications by HPLC-ESI-MS/MS is the gold standard for the quantitative monitoring base oxidation products in both DNA and several body fluids. It should be mentioned that accurate measurement of oxidatively generated base damage requires acute oxidizing conditions. This allows for a significant increase in the yields of oxidized bases/nucleosides above the background level including a significant contribution of adventitious oxidation reactions that cannot be totally suppressed. In a complementary way application of the modified comet assay and alkaline elution technique provides more global information although it gives less structural information about the base damage formed under chronic exposure to mild oxidizing conditions.
Keywords: Oxidatively generated damage to DNA, reactive oxygen and nitrogen species, Hydroxyl Radical, one-electron oxidants, Singlet Oxygen, cellular DNA oxidation, measurement oxidized nucleosides, urinary DNA oxidation lesions
Received: 27 May 2025; Accepted: 24 Jun 2025.
Copyright: © 2025 CADET and Wagner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jean CADET, Université de Sherbrooke, Sherbrooke, Canada
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