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首页> 外文期刊>Mutation research. Genetic toxicology testing >COMPARATIVE MUTAGENICITY TESTING OF CEFTIOFUR SODIUM .1. POSITIVE RESULTS IN IN VITRO CYTOGENETICS
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COMPARATIVE MUTAGENICITY TESTING OF CEFTIOFUR SODIUM .1. POSITIVE RESULTS IN IN VITRO CYTOGENETICS

机译：头孢呋喃钠的致突变性比较测试.1。体外细胞遗传学的阳性结果

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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-64279E, NAXCEL (R), EXCENEL (R)), 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.
机译：对新药进行临床前安全性评估是在将其用于人或动物之前的常规工作，而遗传毒理学分析与其他更传统的毒性测量方法一样，是评估的公认部分。广泛使用的一系列遗传毒理学测定包括Ames沙门氏菌微粒体测定，哺乳动物细胞突变测定，大鼠骨髓微核试验以及用于诱导染色体畸变的体外测定。新一代头孢菌素抗生素头孢噻呋（U-64279E，NAXCEL（R），EXCENEL（R））进行了一系列检测。前三个结果（Ames试验，V79 / HPRT哺乳动物细胞突变试验和微核试验）均为阴性，体外诱导CHO细胞染色体畸变的试验呈阳性结果。观察到的像差的性质主要是染色单体和异染色单体的断裂，缺口和片段，在没有S9代谢活化的情况下几乎没有染色体重排的迹象。仅在长时间（44小时）接触药物后才能观察到畸变增加，在存在S9代谢激活或较短治疗时间的情况下，没有发现致胶裂活性的证据。产生致胶凝作用所需的严格治疗条件也产生了很高水平的有丝分裂抑制作用，因此观察染色体畸变在生物学上不太有意义。

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