Methyl methanesulfonate (MMS) is a well-known classical alkylating agent that induces DNA damage, mutagenesis, and cell dysfunction. Alternatives to mitigate the damage caused by MMS are essential for understanding DNA repair mechanisms and developing approaches to reduce mutagenic and cytotoxic effects of alkylating agents. This study explores the potential of synthetic antioxidants containing iron (1), manganese (2), or copper (3) to protect Saccharomyces cerevisiae from MMS-induced damage. The wild type strain, BY4741, and its isogenic DNA-repair mutants rad9Δ and rad54Δ strains were used to investigate whether these complexes effectively mitigate yeast susceptibility, mitochondrial dysfunction, intracellular oxidation, and mutagenesis caused by MMS. The results demonstrate that all complexes significantly enhanced the survival rates of all fungal strains, indicating their protective role against MMS-induced DNA damage. Additionally, MMS exposure increased mitochondrial dysfunction, intracellular oxidation, and canavanine-based mutagenesis, which was subsequently reduced by the treatment with the complexes, indicating their ability to mitigate oxidative stress and genotoxicity caused by MMS. Among the tested compounds, complex 3 conferred the greatest protective effect against MMS-induced cellular damage, followed by complexes 2 and 1, establishing a consistent order of efficacy: 3 > 2 > 1. These findings demonstrate that the coordination compounds employed in this study effectively protected S. cerevisiae against MMS-induced toxicity, highlighting their potential role in enhancing cellular defense against genotoxic agents.

• PMID: 41045319
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Journal Article

Authors

Mattos LMM, Andrade DA, Alves ANS, Ferreira VT, Oliveira SSC, Segat BB, Santos ALS, Horn A, Fernandes C, Pereira MD

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