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Mutagenicity and mutagenic specificity of metronidazole and niridazole in Neurospora crassa
Abstract:
Mutagenicity and mutagenic specificity of niridazole and metronidazole, two chemotherapeutic agents used in the treatment of human parasitic diseases, were studied with the ad-3 test system of Neurospora crassa. The results show that neither compound is mutagenic in resting conidia. In growing vegetative cells, however, both compounds are mutagenic in N. crassa. Genetic analysis of the mutants indicated that niridazole induces predominantly base-pair substitution mutations. None of the niridazole-induced mutants resulted from multilocus deletions. The spectra of genetic alterations induced by metronidazole are similar to those induced by the mono-functional alkylating agents ethyleneimine (EI), ethylmethanesulfonate (EMS), and ICR-177. It is therefore suggested that the mechanism of mutation induction by metronidazole in Neurospora is similar to that of monofunctional alkylating agents.
Insights
Niridazole and metronidazole are mutagenic in growing Neurospora crassa cells, not resting ones. Niridazole causes base-pair substitutions, while metronidazole
Area of Science:
- Molecular Biology
- Genetics
- Toxicology
Background:
- Niridazole and metronidazole are chemotherapeutic agents for parasitic diseases.
- Understanding their mutagenicity is crucial for therapeutic safety.
Purpose of the Study:
- To assess the mutagenicity and mutagenic specificity of niridazole and metronidazole.
- To elucidate the mechanisms of mutation induction by these agents in Neurospora crassa.
Main Methods:
- Utilized the ad-3 test system in Neurospora crassa.
- Studied mutagenicity in both resting conidia and growing vegetative cells.
- Performed genetic analysis of induced mutants.
Main Results:
- Neither niridazole nor metronidazole showed mutagenicity in resting conidia.
- Both compounds exhibited mutagenicity in growing vegetative cells.
- Niridazole induced primarily base-pair substitution mutations.
- Metronidazole's mutagenic profile resembled that of monofunctional alkylating agents.
Conclusions:
- Niridazole and metronidazole are mutagenic in actively growing Neurospora crassa.
- Niridazole's mechanism involves base-pair substitutions.
- Metronidazole's mutagenic mechanism is suggested to be similar to alkylating agents.