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柔红霉素治疗后急性淋巴细胞白血病细胞所利用的DNA修复途径的测定

Determination of the DNA repair pathways utilised by acute lymphoblastic leukaemia cells following daunorubicin treatment.

作者信息

Al-Aamri Hussain Mubarak, Irving Helen R, Meehan-Andrews Terri, Bradley Christopher

机构信息

Department of Pharmacy and Biomedical Sciences, La Trobe Institute for Molecular Sciences (LIMS), La Trobe University, P.O. Box 199, Bendigo, VIC, 3552, Australia.

Oman College of Health Sciences, PO Box 293, 620, Ruwi, Oman.

出版信息

BMC Res Notes. 2019 Sep 24;12(1):625. doi: 10.1186/s13104-019-4663-8.

DOI:10.1186/s13104-019-4663-8
PMID:31551083
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6760046/
Abstract

OBJECTIVE

DNA double strand breaks (DNA-DSBs) are among the most lethal DNA lesions leading to genomic instability and repaired by either homologous recombination (HR) or the non-homologous end joining (NHEJ) mechanisms. The purpose of this study was to assess the importance and the level of activation of non-homologous end joining (NHEJ) and homologous recombination (HR) DNA repair pathways in three cell lines, CCRF-CEM and MOLT-4 derived from T lymphocytes and SUP-B15 derived from B lymphocytes following treatment with chemotherapy agent daunorubicin.

RESULTS

The Gamma histone H2AX (γH2AX) assay was used assess the effects of DNA-PK inhibitor NU7026 and RAD51 inhibitor RI-2 on repair of DNA-DSB following treatment with daunorubicin. In all cell lines, the NHEJ DNA repair pathway appeared more rapid and efficient. MOLT-4 and CCFR-CEM cells utilised both NHEJ and HR pathways for DNA-DSB repair. Whereas, SUP-B15 cells utilised only NHEJ for DSB repair, suggestive of a deficiency in HR repair pathways.

摘要

目的

DNA双链断裂（DNA-DSBs）是最具致死性的DNA损伤之一，可导致基因组不稳定，通过同源重组（HR）或非同源末端连接（NHEJ）机制进行修复。本研究的目的是评估在用化疗药物柔红霉素处理后，源自T淋巴细胞的CCRF-CEM和MOLT-4以及源自B淋巴细胞的SUP-B15这三种细胞系中，非同源末端连接（NHEJ）和同源重组（HR）DNA修复途径的激活重要性和水平。

结果

使用γ组蛋白H2AX（γH2AX）检测法评估DNA-PK抑制剂NU7026和RAD51抑制剂RI-2对柔红霉素处理后DNA-DSB修复的影响。在所有细胞系中，NHEJ DNA修复途径显得更快且更有效。MOLT-4和CCFR-CEM细胞利用NHEJ和HR途径进行DNA-DSB修复。然而，SUP-B15细胞仅利用NHEJ进行DSB修复，提示HR修复途径存在缺陷。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7db/6760046/a60cc1ed2af6/13104_2019_4663_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7db/6760046/a60cc1ed2af6/13104_2019_4663_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7db/6760046/a60cc1ed2af6/13104_2019_4663_Fig1_HTML.jpg

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