Effects of new quinolone antibacterial agents on mammalian chromosomes.
The clastogenic effects of several new quinolones (ciprofloxacin, enoxacin, levofloxacin, nalidixic acid, ofloxacin, pipemidic acid, and N1-cyclopropyl quinolones for drug candidate) were studied cytogenetically using Chinese hamster lung cells (CHL) and the mouse micronucleus test. Some N1-cyclopropyl quinolones strongly induced chromosomal aberration on CHL cells, and some, but not all, were also capable of inducing micronuclei in mouse bone marrow cells. Levofloxacin showed weak clastogenicity in CHL cells but did not induce either micronuclei in mouse bone marrow or unscheduled DNA synthesis (UDS) in rat hepatocytes when administered to intact live animals. The lack of concordance between in vitro and in vivo assays could reflect the differences in the tissue levels of the drugs and the in vitro conditions.
Shimada
H
H
Developmental Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Itoh
S
S
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D002460:Cell Line; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004260:DNA Repair / Q000187:drug effects; D024841:Fluoroquinolones; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009153:Mutagens