COMPARATIVE MUTAGENICITY TESTING OF CEFTIOFUR SODIUM .2. CYTOGENETIC DAMAGE-INDUCED IN-VITRO BY CEFTIOFUR IS REVERSIBLE AND IS DUE TO CELL-CYCLE DELAY

Ceftiofur, a new generation of cephalosporin antibiotic, used to comba t 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 followi ng treatment for 44 h. No evidence of aberration induction was seen at shorter, i.e., 20 h, treatment time nor was any suggestion of clastog enicity seen in the presence of S9 metabolic activation. The experimen ts reported here were undertaken to determine significance of this obs ervation and elucidate the reason for clastogenesis in the earlier exp eriments. Briefly, ceftiofur was found to not affect the pH or osmolal ity of the treatment solutions nor were enzymes generally associated w ith cell death released during the treatment period. The aberrations w ere found to be reversible, and thus, doubt was cast concerning the po tential for direct DNA damage as a causative factor. The most profound effect of ceftiofur treatment at this level was the dramatic effect o n cell cycle kinetics and therefore the clastogenic effects observed f ollowing exposure to ceftiofur in vitro appear to be due to prolongati on of the cell cycle.