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Genotoxicity studies on the antimicrobial drug sulfamethoxazole in cultured human lymphocytes
Ahmed Abou-Eisha1, Ricard Marcos, Amadeu Creus
1Department of Cell Biology, National Research Center, Dokki, Cairo, Egypt.
Abstract:
The genotoxicity of the antimicrobial drug sulfamethoxazole was evaluated in cultured human peripheral blood lymphocytes. The frequencies of sister-chromatid exchange (SCE) and micronuclei (MN) were scored as genetic endpoints. Both tests cover a wide range of induced genetic damage such as primary DNA damage, clastogenicity and aneugenicity. Cultures were set up with blood samples from two healthy donors and the treatment was done with different sulfamethoxazole concentrations ranging from 10 to 500 microg/ml. From the results obtained it appears that this drug is able to induce weak genotoxic effects, as revealed by the slight increase in the SCE and MN frequencies, at least at one of the two highest concentrations tested. However, the results of the SCE assay should be interpreted with caution because the increase is just significant. In addition, cyotoxic/cytostatic effects of sulfamethoxazole were revealed by a decrease in the proliferative rate index (PRI) and in the cytokinesis block proliferation index (CBPI).
Insights
The antimicrobial drug sulfamethoxazole showed weak genotoxic effects in human cells, indicated by slight increases in sister-chromatid exchange (SCE) and micronuclei (MN) frequencies. Cytotoxic effects were also observed, impacting cell proliferation.
Area of Science:
- Pharmacology
- Genetics
- Toxicology
Background:
- Sulfamethoxazole is a widely used antimicrobial agent.
- Assessing the genotoxicity of pharmaceuticals is crucial for drug safety.
- Genotoxicity testing evaluates potential DNA damage and chromosomal abnormalities.
Purpose of the Study:
- To evaluate the genotoxic potential of sulfamethoxazole in human cells.
- To determine if sulfamethoxazole induces sister-chromatid exchange (SCE) and micronuclei (MN) formation.
- To assess the cytotoxic and cytostatic effects of sulfamethoxazole on lymphocyte proliferation.
Main Methods:
- Cultured human peripheral blood lymphocytes from healthy donors were treated with varying concentrations of sulfamethoxazole (10-500 microg/ml).
- Frequencies of sister-chromatid exchange (SCE) and micronuclei (MN) were analyzed as indicators of genotoxicity.
- Proliferative rate index (PRI) and cytokinesis-block proliferation index (CBPI) were measured to assess cytotoxic/cytostatic effects.
Main Results:
- Sulfamethoxazole treatment resulted in a slight, statistically borderline increase in SCE and MN frequencies at higher concentrations.
- The drug exhibited cytotoxic and cytostatic effects, evidenced by a significant decrease in PRI and CBPI.
- The genotoxic findings suggest weak potential, requiring cautious interpretation due to borderline significance.
Conclusions:
- Sulfamethoxazole demonstrates weak genotoxic potential in human lymphocytes, with borderline significant increases in SCE and MN.
- The drug exhibits clear cytotoxic and cytostatic effects, impacting lymphocyte proliferation.
- Further investigation may be warranted to fully elucidate the genotoxic risk associated with sulfamethoxazole exposure.
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