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[Mutagenicity tests of etoposide and teniposide]
Abstract:
Mutagenicities of Etoposide (VP 16-213) and Teniposide (VM-26), podophyllotoxin derivatives with antitumor activity, were studied by Rec-assay, Salmonella/microsome reverse mutation assay (Ames' test) and Micronucleus test. In the Rec-assay, both Etoposide and Teniposide showed positive results on B. subtilis H17 rec+ and M45 rec-. They also induced the revertants of S. typhimurium TA 98, TA 1537 and TA 1538, but not of S. typhimurium TA 100, TA 1535 or E. coli WP2 uvrA in the Reverse mutation test. The results were not influenced by the addition of S-9 Mix. In the Micronucleus test, Etoposide and Teniposide induced significantly micronucleated polychromatic erythrocytes of the bone marrow cells in mice; 3.3-4.3% at the doses of 0.75-6 mg/kg and 4.0-6.1% at 0.5-4 mg/kg, respectively. These results indicate that Etoposide and Teniposide are both mutagenic.
Insights
Etoposide and Teniposide, antitumor drugs, were found to be mutagenic in bacterial and mouse cell tests. These podophyllotoxin derivatives showed significant genotoxicity, indicating potential risks.
Area of Science:
- Pharmacology
- Toxicology
- Genetics
Context:
- Etoposide (VP 16-213) and Teniposide (VM-26) are podophyllotoxin derivatives used for cancer treatment.
- Assessing the mutagenicity of these drugs is crucial for understanding their safety profile.
Purpose:
- To evaluate the mutagenic potential of Etoposide and Teniposide using multiple genotoxicity assays.
- To determine if these antitumor agents pose a mutagenic risk.
Summary:
- Both Etoposide and Teniposide demonstrated mutagenicity in the Rec-assay using Bacillus subtilis strains.
- These compounds induced reverse mutations in Salmonella typhimurium strains TA98, TA1537, and TA1538, but not in TA100, TA1535, or E. coli WP2 uvrA.
- In vivo micronucleus tests in mice showed that Etoposide and Teniposide significantly increased micronucleated polychromatic erythrocytes, confirming their mutagenic activity.
Impact:
- The findings indicate that Etoposide and Teniposide possess mutagenic properties.
- This research highlights the importance of considering the genotoxic effects of these widely used anticancer agents.
- Results may inform risk-benefit assessments and guide future drug development strategies.