[Study on the genotoxicity of cefuroxime lactone--an impurity substance in antibiotics].

OBJECTIVE

To study the genotoxicity of cefuroxime lactone, a kind of impurity in cefuroxime sodium, and to provide experimental basis for the toxicological safety evaluation of cefuroxime sodium.

METHODS

A set of efficient and convenient genetic toxicity tests were used to evaluate the genotoxicity of cefuroxime lactone, focusing on gene mutation, chromosomal aberration, DNA damage and repair.

RESULTS

(1) Ames assay: The number of colonies with back mutation (revertant) in varied strains of Salmonella typhimurium (TA97, 98, 100 and 102) through all doses of cefuroxime lactone did not exceed the number of spontaneous mutation colony by two times with or without rat liver microsomal enzymes (S9). (2) Micronucleus test in Kunming mice: Micronucleus rate in mice treated with 40 mg/kg cyclophosphamide, which used as a positive control, was 19.74 per thousand, significantly higher than that of negative control (1.82 per thousand) (P < 0.05), and micronucleus rate in mice dosed by 125, 250 and 500 (mg/kg) of cefuroxime lactone were 3.06 per thousand, 2.83 per thousand and 3.24 per thousand, showing no significant difference when compared with the negative control (P > 0.05). (3) Chromosome aberration assay: In the conditions of S9 existence or not, the chromosomal aberration rate of positive control (20 microg/ml cyclophosphamide and 0.1 microg/ml mitomycin c) was significantly higher than that of negative control (P < 0.05), while chromosomal aberration rate from cefuroxime lactone revealed no significant difference compared with the negative control (P > 0.05). (4) TK gene mutation assay: The relative survival (RS), relative viability (RV), relative suspension growth (RSG) and relative total growth (RTG) was decreased along with the increase of cefuroxime lactone concentrations, however, no significant difference was discovered between the dosed groups and negative control for TK gene mutation frequency (P > 0.05). (5) Comet assay: Comet rate of positive control (5.0 microg/ml methyl methanesulfonate) was 94.5%, higher than that of negative control (7.0%) (P < 0.05), while comet rates in varying concentrations of cefuroxime lactone showed no statistically difference compared with the negative control (P > 0.05).

CONCLUSION

genotoxicity was observed under our experimental conditions, which suggested that cefuroxime lactone has no mutagenic effect.