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Published on: April 5, 2015
Iron, manganese, and copper complexes protect saccharomyces cerevisiae from methyl methanesulfonate-induced
Larissa M M Mattos1,2, Davi A Andrade3,4, Alan N S Alves3,4
1Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. larissamattos@pos.iq.ufrj.br.
Abstract:
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.
Insights
Synthetic antioxidants with iron, manganese, and copper protect yeast from methyl methanesulfonate (MMS) DNA damage. These compounds mitigate MMS-induced toxicity, oxidative stress, and mutagenesis, with copper complex showing the highest efficacy.
Area of Science:
- Biochemistry
- Genetics
- Toxicology
Background:
- Methyl methanesulfonate (MMS) is a potent alkylating agent causing DNA damage, mutagenesis, and cellular dysfunction.
- Developing protective agents against MMS is crucial for understanding DNA repair and mitigating genotoxic effects.
- Synthetic antioxidants offer potential strategies to counteract alkylating agent-induced cellular damage.
Purpose of the Study:
- To evaluate the protective potential of synthetic antioxidant complexes containing iron, manganese, and copper against MMS-induced damage in Saccharomyces cerevisiae.
- To investigate the impact of these complexes on yeast survival, mitochondrial function, oxidative stress, and mutagenesis.
- To determine the relative efficacy of different metal-containing complexes in mitigating MMS toxicity.
Main Methods:
- Utilized wild-type (BY4741) and DNA-repair mutant (rad9Δ, rad54Δ) Saccharomyces cerevisiae strains.
- Exposed yeast strains to MMS and treated with iron (1), manganese (2), or copper (3) complexes.
- Assessed survival rates, mitochondrial dysfunction, intracellular oxidation levels, and canavanine mutagenesis.
Main Results:
- All tested metal complexes significantly improved yeast survival rates against MMS exposure.
- Treatment with complexes reduced MMS-induced mitochondrial dysfunction, intracellular oxidation, and mutagenesis.
- Complex 3 (copper) demonstrated the highest protective efficacy, followed by complex 2 (manganese) and complex 1 (iron).
Conclusions:
- Synthetic antioxidant complexes effectively protect Saccharomyces cerevisiae from MMS-induced DNA damage and toxicity.
- These metal-containing compounds mitigate oxidative stress and genotoxicity associated with alkylating agents.
- The findings highlight the potential of these coordination compounds as cellular defense enhancers against genotoxic agents.
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