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Tallysomycin-induced mitotic aneuploidy and point mutations in Aspergillus nidulans
1Department of Biology, University of Patras, Greece.
Abstract:
Tallysomycin is an antibiotic compound structurally related to bleomycin, and like bleomycins and phleomycins also shows antitumour activity. We have investigated the genetic activity of tallysomycin in the ascomycete Aspergillus nidulans for malsegregation of chromosomes at mitosis and for point mutations. We found that the antibiotic at very low concentrations from 0.025 to 0.2 micrograms/ml had an inhibitory effect on colonial growth of up to 50% and it increased the number of mitotic malsegregants from 311% to 607% over the control value. Tallysomycin at concentrations between 2 and 16 micrograms/ml (which inhibited the germination of conidia from 30 to 90%) also increased the number of methionine suppressor revertants from 59 to 368 per 10(6) conidia. With regard to the mechanism for induced mitotic segregation it was shown that this may involve non-disjunction of chromosomes which through the intermediate formation of unstable aneuploids resulted in formation of stable haploid and diploid segregants.
Insights
Tallysomycin, an antibiotic related to bleomycin, induces chromosome missegregation and point mutations in Aspergillus nidulans. This genetic activity was observed at low concentrations, impacting colonial growth and gene function.
Area of Science:
- Microbiology
- Genetics
- Molecular Biology
Background:
- Tallysomycin is an antibiotic compound with structural similarities to bleomycin.
- Bleomycins and phleomycins, like tallysomycin, exhibit antitumour activity.
- Understanding the genetic activity of such compounds is crucial for assessing their safety and potential applications.
Purpose of the Study:
- To investigate the genetic activity of tallysomycin in the ascomycete Aspergillus nidulans.
- To assess tallysomycin's potential to induce chromosome missegregation during mitosis.
- To evaluate tallysomycin's capacity to cause point mutations.
Main Methods:
- Exposure of Aspergillus nidulans to varying concentrations of tallysomycin.
- Quantification of colonial growth inhibition.
- Measurement of mitotic chromosome missegregation rates.
- Assay for point mutations using methionine suppressor reversions.
Main Results:
- Tallysomycin inhibited colonial growth by up to 50% at concentrations of 0.025–0.2 µg/ml.
- Mitotic missegregants increased significantly (311%–607%) over control values.
- Tallysomycin induced point mutations, increasing methionine suppressor revertants from 59 to 368 per 10^6 conidia at 2–16 µg/ml.
Conclusions:
- Tallysomycin exhibits significant genotoxic effects, including chromosome missegregation and point mutations in Aspergillus nidulans.
- The mechanism of induced mitotic segregation likely involves chromosome non-disjunction, leading to aneuploid intermediates and stable segregants.
- These findings highlight the genotoxic potential of tallysomycin, necessitating careful consideration in its use.