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Published on: October 15, 2016
Metronidazole induced DNA damage in somatic cells of Drosophila melanogaster
Ana María Palermo1, Marta Dolores Mudry
1CITEDEF, Juan Bautista de La Salle 4397, B1603ALO, Buenos Aires, Argentina. apalermo@citedef.gov.a
Abstract:
The standard version of the wing somatic mutation and recombination test (SMART) in Drosophila melanogaster was employed in order to evaluate the genotoxic potential of metronidazole (MTZ) as a function of exposure concentration. MTZ was administered by chronic feeding of 3-day-old larvae with the parenteral solution at 0, 500, 1000 and 2000 μg/ml until pupation. The marker-heterozygous progeny (mwh+/+flr3) with phenotypically wild-type wings was analyzed. Non significant differences were found between control and each MTZ concentration tested for single small spots (SSS) frequencies. Large single spots (LSS) and twin spots (TS) were significantly increased with the higher dose. MTZ treatments with 1000 and 2000 μg/ml also significantly increased the frequency of Total spots. These findings suggest that MTZ is genotoxic in the present experimental conditions and induces recombinagenesis and/or gene conversion, two major mechanisms that cause loss of heterocigosity and could play an important role in tumorigenesis and carcinogenesis processes.
Insights
Metronidazole (MTZ) shows genotoxic potential in Drosophila melanogaster wing assays. Higher doses significantly increased mutations, suggesting MTZ induces genetic alterations linked to cancer development.
Area of Science:
- Genetics
- Toxicology
- Developmental Biology
Background:
- Metronidazole (MTZ) is a widely used antibiotic.
- Understanding its genotoxic potential is crucial for risk assessment.
- The wing somatic mutation and recombination test (SMART) is a sensitive assay for genotoxicity.
Purpose of the Study:
- To evaluate the genotoxic potential of metronidazole (MTZ) in Drosophila melanogaster.
- To determine the dose-response relationship of MTZ-induced genotoxicity.
- To investigate the mechanisms of genotoxicity, including recombination and gene conversion.
Main Methods:
- Standard wing somatic mutation and recombination test (SMART) in Drosophila melanogaster.
- Chronic feeding of larvae with MTZ at concentrations of 0, 500, 1000, and 2000 μg/ml.
- Analysis of wing spot frequencies (SSS, LSS, TS, Total spots) in marker-heterozygous progeny.
Main Results:
- No significant increase in single small spot (SSS) frequencies at any MTZ concentration.
- Significant increases in large single spot (LSS) and twin spot (TS) frequencies at higher MTZ doses (1000 and 2000 μg/ml).
- Significant increase in the total spot frequency with MTZ treatment at 1000 and 2000 μg/ml.
Conclusions:
- Metronidazole (MTZ) exhibits genotoxic effects under the tested experimental conditions.
- MTZ induces recombinagenesis and/or gene conversion, leading to loss of heterozygosity.
- These genotoxic mechanisms may contribute to tumorigenesis and carcinogenesis.
