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Detection of fragile sites induced by pyrimethamine
1Department of Medical Biology, Faculty of Medicine, University of Uludağ, Bursa, Turkey.
Abstract:
In this study, the effect of pyrimethamine in inducing expression of fragile sites in human peripheral blood lymphocyte cultures is investigated. In vitro lymphocyte cultures of 15 healthy individuals were treated with 0.02 mg/ml of pyrimethamine for 48 and 72 hr. One culture was used as control. The number of cells showing chromosomal aberration increases significantly in the cultures after 48 and 72 hr in comparison to the control group (P < 0.001). Localization of fragile sites was determined by the G-banding method and light microscopy. As a result, five folic acid-sensitive fragile sites (1p32, 1q32, 3p14, 6p22, 14q24) were detected.
Insights
Pyrimethamine significantly increases chromosomal aberrations in human lymphocytes, revealing five new folic acid-sensitive fragile sites. This finding is crucial for understanding drug-induced genetic instability.
Area of Science:
- Cytogenetics
- Pharmacology
- Human Genetics
Background:
- Fragile sites are specific points on chromosomes prone to breakage.
- Certain drugs can induce or enhance the expression of these fragile sites.
- Understanding these mechanisms is vital for assessing genotoxicity and genetic risk.
Purpose of the Study:
- To investigate the effect of pyrimethamine on inducing fragile sites in human peripheral blood lymphocytes.
- To identify specific chromosomal locations of pyrimethamine-induced fragile sites.
- To evaluate the potential genotoxic effects of pyrimethamine.
Main Methods:
- Human peripheral blood lymphocyte cultures from 15 healthy individuals were established.
- Cultures were treated with pyrimethamine (0.02 mg/ml) for 48 and 72 hours.
- Chromosomal aberrations and fragile site localization (using G-banding and light microscopy) were analyzed.
Main Results:
- A significant increase in cells with chromosomal aberrations was observed in pyrimethamine-treated cultures compared to controls (P < 0.001).
- Five folic acid-sensitive fragile sites were identified and localized: 1p32, 1q32, 3p14, 6p22, and 14q24.
- The study demonstrates pyrimethamine's capacity to induce fragile site expression.
Conclusions:
- Pyrimethamine induces chromosomal instability and expression of fragile sites in human lymphocytes.
- The identified fragile sites (1p32, 1q32, 3p14, 6p22, 14q24) are sensitive to folic acid.
- These findings highlight the importance of considering pyrimethamine's genotoxic potential.