Related Experiment Videos
[Mutagenicity studies of prulifloxacin (NM441) and the active metabolite (NM394)]
K Iwakura1, H Tamura, Y Yamashita
1Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
Abstract:
The mutagenicity of prulifloxacin, a new antibacterial agent, was investigated by the reverse mutation test in bacteria, the chromosomal aberration test in cultured cells, and the micronucleus test in mice. In addition, NM394, an active metabolite of prulifloxacin, was examined for mutagenicity in the chromosomal aberration test in cultured cells. The reverse mutation test was performed at dose range of 0.0078-0.25 micrograms/plate using Salmonella typhimurium strains (TA100, TA1535, TA98, and TA1537), and Escherichia coli (WP2uvrA). Prulifloxacin did not increase revertant colonies significantly in any of the test strains with or without metabolic activation system (S9 mix). The chromosomal aberration tests were carried out in cultured Chinese hamster lung cells (CHL/IU). Prulifloxacin increased aberrant cells without S9 mix, and NM394 also induced chromosomal aberrations. In human lymphocytes, no significant increases of the frequencies of cells with chromosomal aberrations were observed at dose range of 5-320 micrograms/ml with or without S9 mix. The micronucleus test was conducted at doses of 625-5000 mg/kg in the bone marrow cells of Slc : ddY male mice. There were no significant increases in the frequencies of micronucleated polychromatic erythrocytes.
Insights
Prulifloxacin, an antibacterial agent, showed no mutagenicity in bacterial reverse mutation tests or mouse micronucleus tests. However, it induced chromosomal aberrations in cultured Chinese hamster lung cells without metabolic activation.
Area of Science:
- Pharmacology
- Toxicology
- Genetics
Background:
- Prulifloxacin is a novel antibacterial agent.
- Assessing the mutagenicity of new drugs is crucial for safety.
- NM394 is the active metabolite of prulifloxacin.
Purpose of the Study:
- To evaluate the mutagenicity of prulifloxacin and its metabolite NM394.
- To determine potential genotoxic risks associated with prulifloxacin use.
Main Methods:
- Bacterial reverse mutation assay (Ames test) using Salmonella typhimurium and Escherichia coli.
- In vitro chromosomal aberration tests in cultured Chinese hamster lung cells and human lymphocytes.
- In vivo micronucleus test in mouse bone marrow cells.
Main Results:
- Prulifloxacin was not mutagenic in bacterial reverse mutation tests (with or without S9 mix).
- Prulifloxacin induced chromosomal aberrations in Chinese hamster lung cells (without S9 mix).
- NM394 also induced chromosomal aberrations in cultured cells; no significant effects were observed in human lymphocytes or mouse bone marrow cells.
Conclusions:
- Prulifloxacin demonstrated genotoxic potential in vitro (chromosomal aberrations) but not in bacterial assays or in vivo micronucleus tests.
- The active metabolite NM394 also showed in vitro genotoxicity.
- Further investigation may be warranted regarding the in vitro clastogenic effects of prulifloxacin.