[Cytotoxicity and mutagenicity studies of T-3761]

We investigated cytotoxicity and mutagenicity of T-3761. The mutagenicity was evaluated using reverse mutation test with bacteria, chromosome aberration test with cultured cells and micronucleus test with mice. The following results were obtained. 1. Cytotoxicity test: The cell growth was examined using Chinese hamster (V79) cells. The 50% inhibition doses of T-3761 for cell growth (ID50) were 490 micrograms/ml (cultured for 24 hours) and 220 micrograms/ml (cultured for 48 hours). The inhibitory effect of T-3761 was 2-4 times lower than those of ciprofloxacin or norfloxacin and approximately equal to cephalothin. 2. Reverse mutation test with bacteria: The preincubation method with Salmonella typhimurium TA100, TA98, TA1535, TA1537 and Escherichia coli WP2 uvrA, and the induced mutation frequency (IMF) test with Salmonella typhimurium TA100, TA98 were performed. The number of revertant colonies were not increased in any strains treated with T-3761 in the presence or absence of S9 mix. 3. Chromosome aberration test: V79 cells were treated with 50-200 micrograms/ml of T-3761 for 24 or 48 hours, and were treated with 400-3,200 micrograms/ml of T-3761 for 6 hours with S9 mix. The number of cells showing chromosomal aberrations were not increased in any conditions tested for T-3761. 4. Micronucleus test: The male ICR mice were given a single (500-5,000 mg/kg) or five consecutive (150-1,500 mg/kg) oral administration of T-3761. The number of polychromatic erythrocytes with micronuclei were not increased at any dosage groups of T-3761. From these results, it is concluded that T-3761 has low cytotoxicity, and has no mutagenicity.