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Evaluation of the genotoxicity of alpha-amanitin in mice bone marrow cells
B Marciniak1, D Łopaczyńska2, T Ferenc2
1Laboratory of Cytogenetics, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237, Lodz, Poland.
Abstract:
Alpha-amanitin is a known cytotoxic substance found in some mushroom species including Amanita phalloides. Its main mechanism of action is to block the transcription, which can lead to cell death. Lack of reports on the genotoxicity of this toxin was an inspiration for undertaking this experiment. Genotoxic effect of α-amanitin on balb/c mice bone marrow cells was tested using: comet assay and chromosomal aberration test. The tested substance was given once by intraperitoneal administration to animals at doses: 0.1 mg/kg, 0.15 mg/kg and 0.25 mg/kg (LD50) body weight with 48 h exposure. The comet assay demonstrated a statistically significant increase in DNA damage for all the investigated α-amanitin doses compared to the negative control (p < 0.0001). The exposure to 0.15 and 0.25 mg/kg doses of α-amanitin also generated a statistically significant increase in the frequency of chromosomal aberrations in bone marrow cells of mice compared to the negative control (p < 0.05). The genotoxic effect induced by α-amanitin in mammalian cells can result in genome instability and its functional consequences.
Insights
Alpha-amanitin, a toxin from poisonous mushrooms, was found to be genotoxic. This study demonstrated that alpha-amanitin causes DNA damage and chromosomal aberrations in mouse bone marrow cells.
Area of Science:
- Toxicology
- Genetics
- Molecular Biology
Background:
- Alpha-amanitin is a cytotoxic toxin produced by Amanita phalloides mushrooms.
- Its primary mechanism involves blocking transcription, leading to cell death.
- Limited data exists on the genotoxicity of alpha-amanitin.
Purpose of the Study:
- To investigate the genotoxic effects of alpha-amanitin.
- To assess DNA damage and chromosomal aberrations in mammalian cells exposed to alpha-amanitin.
Main Methods:
- Genotoxicity testing was performed on Balb/c mice bone marrow cells.
- Methods included the comet assay and the chromosomal aberration test.
- Mice received single intraperitoneal doses of 0.1, 0.15, or 0.25 mg/kg body weight alpha-amanitin, with a 48-hour exposure period.
Main Results:
- The comet assay showed a significant increase in DNA damage across all tested alpha-amanitin doses (p < 0.0001).
- A significant increase in chromosomal aberrations was observed at 0.15 and 0.25 mg/kg alpha-amanitin doses (p < 0.05).
- These results indicate dose-dependent genotoxic effects.
Conclusions:
- Alpha-amanitin exhibits significant genotoxic potential in mammalian cells.
- The toxin induces DNA damage and chromosomal aberrations.
- This genotoxicity may lead to genome instability and associated functional consequences.
