Cui Jie, Zhang Zunzhen, Ran Yun, Zhao Wei, Kang Xiaoxi, Deng Wenwen
Department of Environmental Health, West China School of Public Health, Sichuan University, Chengdu 610041, China.
Wei Sheng Yan Jiu. 2012 Sep;41(5):717-22.
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.
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.
(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).
genotoxicity was observed under our experimental conditions, which suggested that cefuroxime lactone has no mutagenic effect.
研究头孢呋辛钠中的一种杂质头孢呋辛内酯的遗传毒性，为头孢呋辛钠毒理学安全性评价提供实验依据。
采用一系列高效便捷的遗传毒性试验评估头孢呋辛内酯的遗传毒性，重点关注基因突变、染色体畸变、DNA损伤与修复。
（1）Ames试验：在有或无大鼠肝微粒体酶（S9）存在的情况下，所有剂量的头孢呋辛内酯作用于不同鼠伤寒沙门氏菌菌株（TA97、98、100和102）后，回复突变菌落数均未超过自发突变菌落数的两倍。（2）昆明小鼠微核试验：以40mg/kg环磷酰胺作为阳性对照，其微核率为19.74‰，显著高于阴性对照（1.82‰）（P<0.05）；而125、250和500（mg/kg）头孢呋辛内酯给药组小鼠微核率分别为3.06‰、2.83‰和3.24‰，与阴性对照相比无显著差异（P>0.05）。（3）染色体畸变试验：在有或无S9存在的条件下，阳性对照（20μg/ml环磷酰胺和0.1μg/ml丝裂霉素c）的染色体畸变率显著高于阴性对照（P<0.05），而头孢呋辛内酯的染色体畸变率与阴性对照相比无显著差异（P>0.05）。（4）TK基因突变试验：随着头孢呋辛内酯浓度增加，相对存活率（RS）、相对活力（RV）、相对悬浮生长率（RSG）和相对总生长率（RTG）降低，但给药组与阴性对照的TK基因突变频率无显著差异（P>0.05）。（5）彗星试验：阳性对照（5.0μg/ml甲磺酸甲酯）的彗星率为94.5%，高于阴性对照（7.0%）（P<0.05），不同浓度头孢呋辛内酯的彗星率与阴性对照相比无统计学差异（P>0.05）。
在本实验条件下未观察到遗传毒性，提示头孢呋辛内酯无致突变作用。
