Comparative genotoxicity of quinolone and quinolonyl-lactam antibacterials in the in vitro micronucleus assay in Chinese hamster ovary cells

✍ Scribed by David P. Gibson; Xin Ma; A. Greg Switzer; Vincent A. Murphy; Marilyn J. Aardema

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 135 KB
• Volume: 31
• Category: Article
• ISSN: 0893-6692
• DOI: 10.1002/(sici)1098-2280(1998)31:4<345::aid-em7>3.0.co;2-h

✦ Synopsis

The in vitro micronucleus assay is gaining increased tween 0.02 and 0.16 mM. These changes were larger attention as a potential alternative to the standard than those seen with the commercial quinolones, ciin vitro metaphase analysis assay. In particular, the profloxacin (cytotoxic at ¢ 0.57 mM and MNBC at ¢ in vitro micronucleus assay has been proposed as 0.3 mM) and nalidixic acid (cytotoxic at 1.8 mM and a useful method for chemicals that induce both struc-no MNBC up to this dose). In contrast, the quinolonyltural and numerical chromosome alterations, such lactams were not cytotoxic up to 1.0 mM concentraas DNA gyrase/topoisomerase inhibitors. In this tions and induced either no MNBC or a low frequency study, we compared the micronucleus-inducing ac-of MNBC at higher concentrations compared to the tivity of quinolonyl-lactam antibacterials that inhibit quinolones. Quinolonyl-lactams appear to be less cyto-DNA-gyrase and bind to penicillin-binding proteins toxic and genotoxic than structurally related quinorelative to the activity of structurally related quino-lones. These results add to the growing database on lone antibacterials that also inhibit DNA-gyrase. All the in vitro micronucleus assay in general, and more of the quinolones that were structurally related to specifically to the relatively small database for the in the quinolonyl-lactams were cytotoxic and induced vitro micronucleus assay in Chinese hamster ovary large increases in the frequency of micronucleated cells.