Comparative mutagenicity testing of ceftiofur sodium: I. Positive results in in vitro cytogenetics

Autor: P.R. Harbach, Mazurek Jm, R.L. Yu, D.H. Swenson, R. Marshall, D. Kirkland, C.S. Aaron, S. McEnaney
Rok vydání: 1995
Předmět:
Zdroj: Mutation Research/Genetic Toxicology. 345:27-35
ISSN: 0165-1218
DOI: 10.1016/0165-1218(95)90067-5
Popis: Preclinical safety evaluation of new drugs is routine prior to the use in humans or animals and genetic toxicology assays are an accepted part of the evaluation along with other more traditional measures of toxicity. A widely used battery of genetic toxicology assays includes an Ames Salmonella microsome assay, a mammalian cell mutation assay, a rat bone marrow micronucleus test and an in vitro assay for induction of chromosomal aberrations. Ceftiofur (U-6427E, NAXCEL®, EXCENEL®), a new generation cephalosporin antibiotic, was subjected to this battery of assays. The result of the first three (Ames test, V79/HPRT mammalian cell mutation assay and the micronucleus test) were negative, the in vitro assay for induction of chromosome aberrations in CHO cells gave positive results. The nature of the observed aberrations was primarily chromatid and isochromatid breaks, gaps and fragments with little evidence of chromosomal rearrangements in the absence of S9 metabolic activation. The aberration increase was only seen following an extended (44 h) exposure to drug; no evidence of clastogenic activity was seen in the presence of S9 metabolic activation or at shorter treatment times. The severe treatment conditions required to produce the clastogenic effects also produced very high levels of mitotic inhibition and thus the observation of chromosomal aberrations is unlikely to be biologically meaningful.
Databáze: OpenAIRE
Externí odkaz: