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使用流式细胞术对细胞培养物中的微核频率进行半自动分析,评估核医学中使用的肽(PSMA -617和-11,以及泛素化细胞素29-41)的遗传毒性潜力。

Evaluation of genotoxic potential of peptides used in nuclear medicine (PSMA -617 and -11, and ubiquicidine 29-41) using a flow-cytometric, semi-automated analysis of micronuclei frequency in cell cultures.

作者信息

de Carvalho L R, Vieira D P

机构信息

Laboratório de Radiobiologia, Centro de Biotecnologia, Instituto de Pesquisas Energéticas e Nucleares, Av. Lineu Prestes 2242, São Paulo, São Paulo, Brazil.

出版信息

Toxicol Rep. 2020 Feb 7;7:304-316. doi: 10.1016/j.toxrep.2020.02.003. eCollection 2020.

Abstract

Assays that rely on the assessment of frequency of micronuclei are important standard techniques currently used to quantify potential genotoxic damage after exposure to chemical or physical agents, such as ionizing radiation, or in pre-clinical studies, to assessment of the genotoxic potential of drugs or its components. The experiments are usually performed using conventional microscopy, but currently the protocols are being upgraded to automated approaches based on flow cytometry protocols based on the elimination of the plasma membrane by chemical agents, allowing quantification by flow cytometry. In this work, the genotoxic potential of peptides used as components of radiopharmaceuticals (PSMA-617 and 11 and Ubiquicidine) was evaluated exposing CHO-KI cells to a wide range of concentration (0.1X and 100X the maximum allowed concentration to human adults). Incubation with PSMA-11 or UBI did not induce genotoxicity. After 24 h of incubation, PSMA-617 induced genotoxicity only in non-practical concentration (100-fold). Results corroborate the safety of the pre-drugs and the wide detection range of technique.

摘要

依赖于微核频率评估的检测方法是目前用于量化接触化学或物理因子(如电离辐射)后潜在遗传毒性损伤的重要标准技术,或用于临床前研究中评估药物或其成分的遗传毒性潜力。这些实验通常使用传统显微镜进行,但目前方案正在升级为基于流式细胞术的自动化方法,该方法基于通过化学试剂去除质膜,从而允许通过流式细胞术进行定量。在这项工作中,通过将CHO-KI细胞暴露于广泛的浓度范围(人类成年人最大允许浓度的0.1倍和100倍),评估了用作放射性药物成分的肽(PSMA-617和11以及泛喹啶)的遗传毒性潜力。用PSMA-11或泛喹啶孵育未诱导遗传毒性。孵育24小时后,PSMA-617仅在非实际浓度(100倍)下诱导遗传毒性。结果证实了前体药物的安全性以及该技术的广泛检测范围。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edaa/7016341/522a17e00319/ga1.jpg

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