Vol.55 No.S-1 October 2007
Genotoxicity study of garenoxacin
1)Research Laboratories, Toyama Chemical Co., Ltd., 2-4-1 Shimookui, Toyama, Japan
2)Quality Assurance Center, Toyama Chemical Co., Ltd.
3)Biosafety Research Center, Foods, Drugs and Pesticides
Abstract
A bacterial reverse mutation test, a gene mutation test in mammalian cultured cells, a chromosome aberration test in mammalian cultured cells, a micronucleus test in mice, and an in vivo unscheduled DNA synthesis test in rat hepatocytes were conducted to investigate the genotoxicity of garenoxacin mesilate hydrate(GRNX).
1. In the bacterial reverse mutation test, GRNX did not show mutagenic activity against tester strains (Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli WP2uvrA) in the absence and presence of metabolic activation (S9 mix).
2. In the gene mutation test with cultured mammalian cells (V79 cells), no increase in 6-thioguanine-resistant mutant colonies was observed in the absence and presence of the S9 mix.
3. In the chromosomal aberration test with cultured mammalian cells (CHL/IU cells), increases in the frequency of cells with chromosomal aberration were observed in the absence and presence of the S9 mix.
4. In the micronucleus test in mice, no increase was observed in the frequency of micronuclei.
5. In the in vivo unscheduled DNA synthesis test in rat hepatocytes, no increase of the number was observed with net nuclear grain and repair cells.
These results indicated that GRNX showed mutagenic activity against cultured mammalian cells based on its topoisomerase inhibitory activity, but not in the mice micronucleus test or other in vitro and in vivo studies. The GRNX is thus not considered to show the mutagenic activity in vivo.
Key word
garenoxacin, des-fluoro(6)-quinolone, genotoxicity
Received
May 11, 2007
Accepted
July 6, 2007
Jpn. J. Chemother. 55 (S-1): 54-61, 2007
