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In vitro cytotoxic and genotoxic evaluation of peptides used in nuclear medicine (DOTATATE and Ubiquicidin29-41) in CHO-K1 cells

机译:CHO-K1细胞中核医学用肽(DOTATATE和Ubiquicidin29-41)的体外细胞毒性和遗传毒性评估

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摘要

Micronucleus (MN) assay constitutes a valuable surrogate to the chromosome aberration technique for in vitro testing of the genotoxicity of substances. As test substances, two peptidic compounds (DOTATATE and Ubiquicidin29-41) used in nuclear medicine, were tested for in vitro cytotoxicity and genotoxicity in CHO-K1 cells. None of the compounds showed detectable cytotoxicity (0.5–7.3?ng/mL for DOTATATE and 0.3–4.5?ng/mL for UBI29-41), genotoxicity (0.72, 7.2 and 72.0?ng/ml for DOTATATE and 0.45, 4.5 and 45.0?ng/mL for UBI29-41) or cell cycle changes as compared to untreated controls at the concentrations tested. Statistical analysis showed good concordance between two independent analysts. The results corroborate the notion of the safety of the compounds and present improvements of the in vitro MN assay when performed in a pre-clinical trial context that increase the throughput of small-to-medium testing facilities as an alternative to high content screening systems.
机译:微核(MN)分析构成了用于体外测试物质遗传毒性的染色体畸变技术的宝贵替代品。作为测试物质,测试了核医学中使用的两种肽化合物(DOTATATE和Ubiquicidin29-41)在CHO-K1细胞中的体外细胞毒性和基因毒性。没有一种化合物显示出可检测到的细胞毒性(DOTATATE为0.5–7.3?ng / mL,UBI29-41为0.3–4.5?ng / mL),遗传毒性(DOTATATE为0.72、7.2和72.0?ng / ml和0.45、4.5和45.0)与未处理的对照组相比,UBI29-41的浓度为?ng / mL)或细胞周期发生了变化。统计分析表明,两位独立分析师之间具有很好的一致性。结果证实了化合物安全性的概念,并在临床前试验中进行了体外MN测定的改进,这增加了中小型测试设施的通量,可替代高含量筛选系统。

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