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Nitrofuran induced mutagenesis and error prone repair in Escherichia coli
Abstract:
Nitrofuran derivatives are a class of compounds which exhibit mutagenic and cytotoxic effects in bacteria and mammalian cells in tissue culture after metabolic activation by endogenous nitroreductases. The relationship between mutation and induction of pleiotropic error-prone repair functions (the 'SOS' system) in bacteria following exposure to nitrofurans was examined. A variety of nitrofurans were found to induce protein X, the recA+ protein, which is characteristic of error-prone repair. Furthermore, induction of the 'SOS' system depended on reductive activation of the mutagen. The use of a mutant thermally inducible for error-prone repair functions (tif-1) provided direct examination of bacteria exposed to non-lethal doses of nitrofuran. These results distinguish between mutants which arose from directly induced base mispairing and those which occur only after induction of error-prone repair functions. The mutational activity of AF2 (furylfuramide) was almost entirely dependent on the induction of error-prone repair since very few tryptophan revertants were detected in conditions which did not induced the 'SOS' repair system. We present a model for mutation induction by nitrofurans in bacteria.
Insights
Nitrofuran compounds can cause mutations by activating error-prone repair systems in bacteria. This study details how these mutagens induce the
Area of Science:
- Microbiology
- Molecular Biology
- Toxicology
Background:
- Nitrofuran derivatives are known mutagens and cytotoxins.
- Metabolic activation by nitroreductases is required for nitrofuran activity.
- The 'SOS' system in bacteria involves error-prone repair functions.
Purpose of the Study:
- To investigate the relationship between nitrofuran-induced mutations and the bacterial 'SOS' system.
- To understand the role of reductive activation in nitrofuran mutagenicity.
- To differentiate mutation mechanisms in bacteria exposed to nitrofurans.
Main Methods:
- Exposure of bacterial strains to various nitrofurans.
- Assaying for induction of protein X (recA+ protein) as a marker for error-prone repair.
- Utilizing a thermally inducible mutant (tif-1) for studying non-lethal doses.
- Analyzing tryptophan revertants to assess mutational activity.
Main Results:
- Nitrofurans induce protein X, indicating activation of error-prone repair.
- Induction of the 'SOS' system is dependent on reductive activation of the mutagen.
- Mutational activity, particularly of AF2 (furylfuramide), relies heavily on the 'SOS' repair system.
- A distinction was made between mutations from direct base mispairing and those from induced repair functions.
Conclusions:
- Nitrofuran-induced mutations in bacteria are largely mediated by the 'SOS' error-prone repair system.
- Reductive activation is crucial for nitrofuran mutagenicity.
- A model for nitrofuran mutation induction in bacteria has been proposed.