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[Mutagenicity and carcinogenicity of nabumetone]
Abstract:
To study the mutagenicity and carcinogenicity of Nabumetone, we conducted Ames test (TA97, TA98, TA100, TA102), micronucleus test(MN) in mice marrow, chromosomal aberration assay(CA) in CHL cells in vitro, CA in germ cells from testes of mice, and cell transformation test of Syrian hamster embryo(SHE) cells. The maximum concentration was 500 micrograms/plate in Ames test with and without S9 mix. The mice were treated orally(gavage) daily for 4 days in 3 doses in which the maximum dose was 60% LD50 and sampled at the 5th day in MN. The maximum concentration was the dose that the growth of 50% of cells was inhibited in CA of CHL. Cells were harvested after recultured for 18 hours in fresh medium after treatment for 6 hours in the test with S9 mix, and after treatment for 24 or 48 hours in the without S9 mix. The mice were treated orally(gavage) daily for 5 days in 3 doses in which the maximum dose was 1/4 LD50 and sampled at the 6th day in CA of germ cells from testes of mice. 2 micrograms/ml was chosen as the maximum concentration in the cell transformation test of SHE cells, and result was observed after treatment for 9 days, All the tests obtained the same negative result as that reported by other investigators.
Insights
Nabumetone was evaluated for mutagenicity and carcinogenicity using multiple assays. All tests, including Ames, micronucleus, and chromosomal aberration tests, yielded negative results, indicating no mutagenic or carcinogenic potential.
Area of Science:
- Toxicology
- Genetics
- Carcinogenesis
Background:
- Nabumetone is a non-steroidal anti-inflammatory drug (NSAID).
- Assessing the mutagenicity and carcinogenicity of pharmaceutical compounds is crucial for drug safety.
- Previous studies have investigated aspects of Nabumetone's toxicological profile.
Purpose of the Study:
- To comprehensively evaluate the mutagenic and carcinogenic potential of Nabumetone.
- To confirm or refute findings from previous investigations regarding Nabumetone's genotoxicity.
Main Methods:
- Ames test (bacterial reverse mutation assay) using strains TA97, TA98, TA100, and TA102.
- In vitro chromosomal aberration assay in Chinese hamster lung (CHL) cells.
- In vivo micronucleus test in mouse bone marrow.
- In vivo chromosomal aberration assay in germ cells of mice testes.
- In vitro Syrian hamster embryo (SHE) cell transformation test.
Main Results:
- All conducted assays, including Ames tests (with and without S9 mix), micronucleus tests, chromosomal aberration assays (in vitro and in vivo), and the SHE cell transformation test, produced negative results.
- The negative outcomes were consistent across all tested concentrations and experimental conditions.
- No evidence of mutagenicity or carcinogenicity was detected for Nabumetone under the study's conditions.
Conclusions:
- Nabumetone demonstrated no mutagenic or carcinogenic activity in the conducted battery of tests.
- The findings support the safety profile of Nabumetone concerning genotoxicity and carcinogenicity.
- These results align with previously reported data on Nabumetone's toxicological effects.