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Published on: August 6, 2014
The cytogenetic effects of pyrimethamine on male mouse germ cells
1Department of Biology, Faculty of Arts and Science, Uludağ University, Bursa, Turkey.
Abstract:
Pyrimethamine is an inhibitor of dihydrofolate reductase and is used in the treatment of malaria and toxoplasmosis. We examined the cytogenetic effects of this drug. Adult male mice were given doses of 20, 40, 80, and 120 mg/kg pyrimethamine intraperitoneally. Animals were killed by cervical dislocation on the 3rd, 6th, 9th, and 12th day after treatment, and the primary spermatocytes were harvested from their testes. These cells were analyzed for gaps, breaks, acentric fragments, and exchanges, as well as for numerical aberrations such as univalency. A dose-related increase in chromosomal aberrations was found in the pyrimethamine group compared with the control group. We suspect that pyrimethamine is a possible clastogen that may affect human germ cells.
Insights
Pyrimethamine, used for malaria and toxoplasmosis, may cause DNA damage. This study found increased chromosomal aberrations in male mice treated with pyrimethamine, suggesting a potential risk to human germ cells.
Area of Science:
- Toxicology
- Genetics
- Pharmacology
Background:
- Pyrimethamine is a dihydrofolate reductase inhibitor.
- It is clinically used for malaria and toxoplasmosis treatment.
Purpose of the Study:
- To investigate the cytogenetic effects of pyrimethamine.
- To assess the potential clastogenicity of pyrimethamine in male germ cells.
Main Methods:
- Adult male mice were administered varying doses of pyrimethamine (20-120 mg/kg).
- Primary spermatocytes were harvested on days 3, 6, 9, and 12 post-treatment.
- Chromosomal aberrations (gaps, breaks, exchanges, numerical aberrations) were analyzed.
Main Results:
- A dose-dependent increase in chromosomal aberrations was observed in pyrimethamine-treated mice.
- Specific aberrations included gaps, breaks, acentric fragments, exchanges, and univalency.
Conclusions:
- Pyrimethamine demonstrated clastogenic potential in male mouse germ cells.
- The drug may pose a risk to human germ cell integrity.
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