Lack of mutagenicity of levofloxacin in lacZ transgenic mice

The mutagenic effects of levofloxacin in lacZ transgenicmice(Muta^TMMouse) have been investigated. Male Muta^TMMouse micewere administered levofloxacin i.p. at a dose of 300 or 600mg/kg. The higher dose corresponded to half the LD50 of thecompound in ddY strain mice. The mutant frequencies in the bonemarrow, liver (day 10 only), testis and sperm were examinedby the positive selection method for lacZ mutations on days1 and 10 after treatment Levofloxacin did not induce any statisticallysignificant increase in mutant frequency in any of the examinedtissues at either dose level or at either sampling time. Themutant frequency increases over the spontaneous values in thebone marrow, liver, testis and sperm were 1.0- to 1.2-fold,0.9-fold, 0.5- to 1.0-fold and 0.9- to 13-fold respectively.N-Ethyl-N-nitrosourea (100 mg/kg as a positive control), onthe other hand, induced significant increases in mutant frequenciesin both somatic cells (bone marrow and liver) and germ cells(testis and sperm) on day 10 after treatment. The mutagenicpotency for ENU was bone marrow >> liver testis sperm(50.1-fold, 3.4-fold, 2.9-fold and 23-fold respectively overthe spontaneous values). Levofloxacin was not mutagenic in thelacZ transgenic mice under the present experimental conditions. ¹To whom correspondence should be addressed. Tel: +81 3 5696 8294; Fax: +81 3 5696 8335; Email: itohsudk{at}daiichipharm.co.jp