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Genotoxic effects of rotenone on cultured lymphocytes
Patrícia Danielle Lima de Lima1, Elizabeth Sumi Yamada, Edmar Tavares da Costa
1Laboratório de Citogenética Humana, Departamento de Biologia, Centro de Ciências Biológicas, Hospital Universitário João de Barros Barreto, Universidade do Pará, Belém, PA, Brasil.
Abstract:
Rotenone is a heterocyclic compound widely used as an insecticide, acaricide and piscicide. Its toxicity is mainly caused by the inhibition of mitochondrial respiratory processes and ATP production, resulting in the generation of reactive oxygen species. Reactive oxygen species can interact with DNA, RNA and proteins, leading to cell damage, followed by death. We used the Comet assay, and we analyzed chromosome aberrations, in order to evaluate the genotoxic and clastogenic effects of rotenone on the different phases of the cell cycle. Cultured human lymphocytes were treated with 1.0, 1.5 and 2.0 microg/mL rotenone during the G1, G1/S, S (pulses of 1 and 6 h), and G2 phases of the cell cycle. Rotenone induced DNA damage and was clastogenic, but the clastogenicity was detected only with treatments conducted during the G1/S and S phases of the cell cycle. Rotenone also induced endoreduplication and polyploidy in treatments made during G1, while it significantly reduced the mitotic index in all phases of the cell cycle.
Insights
Rotenone, a pesticide, causes DNA damage and chromosome aberrations in human cells. Its genotoxic effects vary depending on the cell cycle phase, with clastogenicity observed during G1/S and S phases.
Area of Science:
- Toxicology
- Cell Biology
- Genetics
Background:
- Rotenone is a widely used insecticide, acaricide, and piscicide.
- Its toxicity stems from inhibiting mitochondrial respiration, reducing ATP production, and generating reactive oxygen species (ROS).
- ROS can damage DNA, RNA, and proteins, leading to cellular damage and death.
Purpose of the Study:
- To evaluate the genotoxic and clastogenic effects of rotenone on human lymphocytes.
- To assess these effects across different phases of the cell cycle (G1, G1/S, S, and G2).
Main Methods:
- Utilized the Comet assay to detect DNA damage.
- Analyzed chromosome aberrations to assess clastogenic effects.
- Treated cultured human lymphocytes with varying concentrations of rotenone (1.0, 1.5, 2.0 microg/mL) during specific cell cycle phases.
Main Results:
- Rotenone induced DNA damage and exhibited clastogenic effects, particularly when applied during the G1/S and S phases.
- Treatments during the G1 phase led to endoreduplication and polyploidy.
- A significant reduction in the mitotic index was observed across all treated cell cycle phases.
Conclusions:
- Rotenone demonstrates genotoxic and clastogenic potential in human lymphocytes.
- The observed effects are cell cycle-dependent, with distinct impacts on DNA integrity and chromosomal structure.
- Rotenone's mechanism involves inducing DNA damage, aberrations, and alterations in cell cycle progression, contributing to its toxicity.
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