COMPARATIVE GENOTOXICITY OF QUINOLONE AND QUINOLONYL-LACTAM ANTIBACTERIALS IN THE IN-VITRO MICRONUCLEUS ASSAY IN CHINESE-HAMSTER OVARY CELLS

The in vitro micronucleus assay is gaining increased attention as a po tential alternative to the standard in vitro metaphase analysis assay. In particular, the in vitro micronucleus assay has been proposed as a useful method For chemicals that induce both structural and numerical chromosome alterations, such as DNA gyrase/topoisomerase inhibitors. In this study, we compared the micronucleus-inducing activity of quino lanyl-lactam antibacterials that inhibit DNA-gyrase and bind ta penici llin-binding proteins relative to the activity of structurally related quinolone antibacterials that also inhibit DNA-gyrase. All of the qui nolones that were structurally related to the quinolonyl-lactams were cytotoxic and induced large increases in the Frequency of micronucleat ed binucleated cells (MNBC) at concentrations between 0.02 and 0.16 mM . These changes were larger than those seen with the commercial quinol ones, ciprofloxacin (cytotoxic at greater than or equal to 0.57 mM and MNBC at greater than or equal to 0.3 mM) and nalidixic acid (cytotoxi c at 1.8 mM and no MNBC up to this dose). In contrast, the quinolonyl- lactams were not cytotoxic up to 1.0 mM concentrations and induced eit her no MNBC or a low frequency of MNBC at higher concentrations compar ed to the quinolones. Quinolonyl-lactams appear to be less cytotoxic a nd genotoxic than structurally related quinotones. These results add t o the growing database on the in vitro micronucleus assay in general, and more specifically to the relatively small database for the in vitr o micronucleus assay in Chinese hamster ovary cells. (C) 1998 Wiley-Li ss, Inc.