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细胞有丝分裂阻断微核细胞胞质分裂法演变为一种更全面的染色体不稳定性测量方法。

Cytokinesis-Block Micronucleus Cytome Assay Evolution into a More Comprehensive Method to Measure Chromosomal Instability.

机构信息

Genome Health Foundation, North Brighton, SA 5048, Australia.

Centre for Healthy Aging and Wellness, Faculty of Health Science, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia.

出版信息

Genes (Basel). 2020 Oct 15;11(10):1203. doi: 10.3390/genes11101203.

DOI:10.3390/genes11101203
PMID:33076531
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7602810/
Abstract

This review describes the cytokinesis-block micronucleus (CBMN) cytome assay and its evolution into a molecular cytogenetic method of chromosomal instability (CIN). Micronuclei (MNi) originate from whole chromosomes or chromosome fragments that fail to segregate to the poles of the cell during mitosis. These lagging chromosomes are excluded from the daughter nuclei and are enveloped in their own membrane to form MNi. The CBMN assay was developed to allow MNi to be scored exclusively in once-divided binucleated cells, which enables accurate measurement of chromosome breakage or loss without confounding by non-dividing cells that cannot express MNi. The CBMN assay can be applied to cell lines in vitro and cells such as lymphocytes that can be stimulated to divide ex vivo. In the CBMN assay, other CIN biomarkers such as nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) are also measured. Use of centromere, telomere, and chromosome painting probes provides further insights into the mechanisms through which MNi, NPBs and NBUDs originate. Measurement of MNi is also important because entrapment within a micronucleus may cause chromosomes to shatter and, after nuclear reintegration, become rearranged. Additionally, leakage of DNA from MNi can stimulate inflammation via the cyclic GMP-AMP Synthase-Stimulator of Interferon Genes (cGAS-STING) DNA sensing mechanism of the innate immune system.

摘要

本文综述了胞质分裂阻断微核（CBMN）细胞遗传学检测法及其向染色体不稳定性（CIN）分子细胞遗传学检测法的演变。微核（MNi）来源于在有丝分裂过程中未能向细胞两极分离的整条染色体或染色体片段。这些滞后染色体被排除在子核之外，并被包裹在自己的膜中形成 MNi。CBMN 检测法的开发是为了允许仅在一次分裂的双核细胞中对 MNi 进行评分，从而能够准确测量染色体断裂或丢失，而不会受到无法表达 MNi 的非分裂细胞的干扰。CBMN 检测法可应用于体外细胞系和可刺激体外分裂的淋巴细胞等细胞。在 CBMN 检测法中，还测量了其他 CIN 生物标志物，如核质桥（NPB）和核芽（NBUD）。使用着丝粒、端粒和染色体涂染探针可以进一步深入了解 MNi、NPB 和 NBUD 起源的机制。测量 MNi 也很重要，因为微核内的捕获可能导致染色体破碎，并且在核再整合后，发生重排。此外，MNi 中的 DNA 泄漏可以通过先天免疫系统的环鸟苷酸-腺苷酸合成酶-干扰素基因刺激物（cGAS-STING）DNA 感应机制引发炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc70/7602810/279beb72973c/genes-11-01203-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc70/7602810/005c04be51aa/genes-11-01203-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc70/7602810/fd56ed14cc8b/genes-11-01203-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc70/7602810/cfee5f59c0fd/genes-11-01203-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc70/7602810/892f14a9322c/genes-11-01203-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc70/7602810/8b6d9b8e26b3/genes-11-01203-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc70/7602810/b387763e5c44/genes-11-01203-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc70/7602810/279beb72973c/genes-11-01203-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc70/7602810/005c04be51aa/genes-11-01203-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc70/7602810/fd56ed14cc8b/genes-11-01203-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc70/7602810/cfee5f59c0fd/genes-11-01203-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc70/7602810/892f14a9322c/genes-11-01203-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc70/7602810/8b6d9b8e26b3/genes-11-01203-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc70/7602810/b387763e5c44/genes-11-01203-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc70/7602810/279beb72973c/genes-11-01203-g007.jpg

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