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使用细胞遗传学和分子方法研究多黏菌素E的遗传毒性作用。

Investigation of genotoxic effects of doripenem using cytogenetic and molecular methods.

作者信息

Aydin M, Rencüzoğullari E, Bozkurt O, Genç A, Bayram S

机构信息

Departmant of Biology, Faculty of Science and Letters, Adiyaman University, Adiyaman, Turkey.

Departmant of Biology, Natural and Applied Sciences Institute, Adiyaman University, Adiyaman, Turkey.

出版信息

Cell Mol Biol (Noisy-le-grand). 2017 Oct 31;63(10):87-92. doi: 10.14715/cmb/2017.63.10.14.

DOI:10.14715/cmb/2017.63.10.14
PMID:29096747
Abstract

The main aim of this study was to investigate the genotoxic effects of doripenem (DRP) using both cytogenetic and molecular test systems. Although there have been some studies reporting the effects of DRP, none of them has shown the genotoxic effects of DRP. In order to achieve the main aim of the study, the human peripheral lymphocytes were treated with 100 μg/ml, 200 μg/ml, and 400 μg/ml concentrations of DRP for 24 and 48 hours, and the chromosome aberration (CA) and micronucleus (MN) methods were used as the cytogenetic tests and RAPD-PCR method was used as the molecular test to determine the genotoxic effects of DRP. DRP did not induce the chromosome aberrations and micronucleus frequencies at all concentrations and at all treatment periods. So, it was concluded that DRP did not show any cytotoxic effect. However, DRP increased the number of polymorphic bands and decreased the ratio of genomic template stability, especially at the 48-hour treatment period. In this study, according to the obtained results, it was determined that DRP failed to show any genotoxic risk at the therapeutic doses. This result also indicates that DRP could be a reliable antibiotics according to its rapid metabolism.

摘要

本研究的主要目的是使用细胞遗传学和分子检测系统来研究多黏菌素B(DRP)的遗传毒性作用。尽管已有一些研究报道了DRP的作用,但均未显示出DRP的遗传毒性作用。为实现本研究的主要目的,将人外周血淋巴细胞分别用100μg/ml、200μg/ml和400μg/ml浓度的DRP处理24小时和48小时,并采用染色体畸变(CA)和微核(MN)方法作为细胞遗传学检测,采用随机扩增多态性DNA -聚合酶链反应(RAPD-PCR)方法作为分子检测来确定DRP的遗传毒性作用。在所有浓度和所有处理时间段,DRP均未诱导染色体畸变和微核频率。因此,得出结论:DRP未显示出任何细胞毒性作用。然而,DRP增加了多态性条带的数量并降低了基因组模板稳定性的比率,尤其是在48小时处理时间段。在本研究中,根据所得结果确定,在治疗剂量下DRP未显示出任何遗传毒性风险。该结果还表明,根据其快速代谢情况,DRP可能是一种可靠的抗生素。

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