[Mutagenicity studies of prulifloxacin (NM441) and the active metabolite (NM394)].

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.