Comparative mutagenicity testing of ceftiofur sodium II. Cytogenitic damage induced in vitro by ceftiofur is reversible and is due to cell cycle delay

  • Aaron C
  • Yu R
  • Bacon J
 et al. 
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Abstract

Ceftiofur, a new generation of cephalosporin antibiotic, used to combat bacterial respiratory disease in growing cattle and swine, has been tested in a battery of genetic toxicology assays (Aaron et al., 1995a) and been shown to produce chromosome aberrations in CHO cells following treatment for 44 h. No evidence of aberration induction was seen at shorter, i.e., 20 h, treatment time nor was any suggestion of clastogenicity seen in the presence of S9 metabolic activation. The experiments reported here were undertaken to determine significance of this observation and elucidate the reason for clastogenesis in the earlier experiments. Briefly, ceftiofur was found to not affect the pH or osmolality of the treatment solutions nor were enzymes generally associated with cell death released during the treatment period. The aberrations were found to be reversible, and thus, doubt was cast concerning the potential for direct DNA damage as a causative factor. The most profound effect of ceftiofur treatment at this level was the dramatic effect on cell cycle kinetics and therefore the clastogenic effects observed following exposure to cettiofur in vitro appear to be due to prolongation of the cell cycle. © 1995.

Author-supplied keywords

  • Antibiotic mutagenesis
  • Cell cycle effect
  • Clastogenesis
  • Extreme treament condition
  • Preclinical safety assessment

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