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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 Neurospora crassa. Genetic analysis of the mutants indicate 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 monofunctional alkylating agents, EI, EMS and ICR-177. It is suggested, therefore, that the mechanism of mutation induction by metronidazole in Neurospora is similar to that of monofunctional alkylating agents.
Insights
Niridazole and metronidazole are not mutagenic in resting cells but are mutagenic in growing Neurospora crassa cells. Niridazole causes base-pair substitutions, while metronidazole
Area of Science:
- Microbiology
- Genetics
- Toxicology
Background:
- Niridazole and metronidazole are chemotherapeutic agents used for parasitic diseases.
- Understanding their mutagenicity is crucial for assessing therapeutic safety.
Purpose of the Study:
- To evaluate the mutagenicity and mutagenic specificity of niridazole and metronidazole.
- To compare their mechanisms of action in Neurospora crassa.
Main Methods:
- Utilized the ad-3 test system of Neurospora crassa.
- Assessed mutagenicity in both resting conidia and growing vegetative cells.
- Performed genetic analysis of induced mutations.
Main Results:
- Neither niridazole nor metronidazole showed mutagenicity in resting conidia.
- Both compounds demonstrated mutagenicity in growing vegetative cells.
- Niridazole primarily induced base-pair substitution mutations.
- Metronidazole's mutation spectrum resembled that of monofunctional alkylating agents.
Conclusions:
- Niridazole and metronidazole exhibit mutagenic potential in actively growing cells.
- Niridazole acts via base-pair substitutions.
- Metronidazole's mutagenic mechanism may involve alkylation-like processes.