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硝基咪唑衍生物:人外周血淋巴细胞中的非随机性姐妹染色单体交换

Nitroimidazole derivatives: non-randomness sister chromatid exchanges in human peripheral blood lymphocytes.

作者信息

Ana Carballo Marta, Martinez Romari Alejandra, Mudry Marta Dolores

机构信息

CIGETOX-Citogenética Humana y Genética Toxicológica, Departamento Bioquímica Clínica. INFIBIOC, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956 (1113), Ciudad Autónoma de Buenos Aires, Argentina.

出版信息

J Appl Toxicol. 2009 Apr;29(3):248-54. doi: 10.1002/jat.1403.

Abstract

Nitroimidazole derivatives exhibited genotoxic effect in different experimental conditions. This study focuses on an evaluation of possible genomic targets, at a chromosomal level, of two 5-nitroimidazoles (ornidazole and metronidazole) using the in vitro human peripheral blood culture as experimental system. We observed that both derivatives showed a decrease in mitotic index (MI) (P < 0.001), an increase in sister chromatid exchanges (SCE) frequency (P < 0.001) and no modifications in cellular proliferation kinetics (CPK). As a null hypothesis we considered the assumption that larger chromosomes should harbor more SCE, which was viewed using a novel sequential G-band (400 band resolution)/SCE technique. The analysis showed highly significant chi square values (P < 0.001), indicating that SCE frequency per chromosome is not proportional to chromosome length. SCE could be considered an instability indicator due to the high correlation between SCEs in certain chromosomal bands and the exposure to nitroimidazole derivatives.

摘要

硝基咪唑衍生物在不同实验条件下表现出遗传毒性作用。本研究以体外人外周血培养为实验系统,着重评估两种5 - 硝基咪唑(奥硝唑和甲硝唑)在染色体水平上可能的基因组靶点。我们观察到,这两种衍生物的有丝分裂指数(MI)均下降(P < 0.001),姐妹染色单体交换(SCE)频率增加(P < 0.001),而细胞增殖动力学(CPK)无变化。作为零假设,我们考虑这样一种假设,即较大的染色体应含有更多的SCE,这是使用一种新颖的连续G带(400带分辨率)/SCE技术进行观察的。分析显示卡方值高度显著(P < 0.001),表明每条染色体的SCE频率与染色体长度不成比例。由于某些染色体带中的SCE与接触硝基咪唑衍生物之间存在高度相关性,SCE可被视为一种不稳定性指标。

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