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Mutagenicity tests on epristeride in vitro and in vivo
1Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
Aim:
To evaluate the genetic effects of epristeride (Epr), a new prospective drug for treating benign prostatic hyperplasia.
Methods:
1) Assaying reverse mutation in histidine nutritional deficiency strain of Salmonella typhimurium 2) detecting chromosome aberrations in Chinese hamster lung cells (CHL); 3) micronucleus assays of mouse bone marrow; 4) counting sperm shape abnormalities 35 d after first ig Epr.
Results:
1) The reverse mutation happened at almost the same rate of the negative control. Epr did not induce bacterial mutation. 2) In vitro, the rates of aberration were all below 3%, thus Epr did not induce chromosome damage in CHL. 3) Micronucleated polychromatic erythroblasts (PCE) were not apparently more than those of sovent control, Epr did not induce the formation of micronuclei in PCE. 4) With Epr 818, 682, and 341 mg.kg-1, the head abnormalities of sperms were 5.3% +/- 2.7%, 5.3% +/- 1.9%, and 5.2% +/- 1.2%, respectively.
Conclusion:
No genetic toxicity of Epr was detected.
Insights
Epristeride (Epr), a potential treatment for benign prostatic hyperplasia, showed no signs of genetic toxicity in bacterial or mammalian cell assays. Further studies confirmed no genotoxic effects in mouse bone marrow or sperm abnormalities.
Area of Science:
- Pharmacology
- Toxicology
- Genetics
Background:
- Benign prostatic hyperplasia (BPH) is a common condition in aging men.
- Epristeride (Epr) is a novel drug candidate for BPH treatment.
- Evaluating the genotoxicity of new pharmaceutical agents is crucial.
Purpose of the Study:
- To assess the potential genetic toxicity of epristeride (Epr).
- To determine if Epr induces mutations or chromosomal damage.
Main Methods:
- Bacterial reverse mutation assay (Ames test) using Salmonella typhimurium.
- In vitro chromosome aberration test in Chinese hamster lung cells (CHL).
- In vivo micronucleus assay in mouse bone marrow and sperm morphology analysis.
Main Results:
- Epristeride did not induce bacterial reverse mutations.
- No significant chromosome aberrations were observed in CHL cells treated with Epr.
- Epr did not increase micronuclei formation in mouse bone marrow.
- Sperm abnormality rates remained comparable to controls across different Epr doses.
Conclusions:
- Epristeride demonstrated no genotoxic potential in the conducted assays.
- The findings suggest Epr is safe from a genetic toxicity perspective.