Cytokinesis-block micronucleus assay evolves into a "cytome" assay of chromosomal instability, mitotic dysfunction and cell death
Cytokinesis-block micronucleus assay evolves into a "cytome" assay of chromosomal instability, mitotic dysfunction and cell death
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DOI：
10.1016/j.mrfmmm.2006.05.028
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发表时间：
2006-08-30
影响因子：
2.3
通讯作者：
Fenech, Michael
中科院分区：
文献类型：
--
作者：
Fenech, Michael
胞质分裂阻断微核(CBMN)最初是一种测量微核(MNI)的理想系统，但它也可用于测量核质桥(NPB)、核芽(NBUD)、细胞死亡(坏死或凋亡)和核分裂率。目前的证据表明：(A)NPB起源于双着丝粒染色体，其中着丝粒在后期被拉到细胞的相反两极，因此表明DNA错误修复、染色体重排或端粒末端融合，(B)NPB可能断裂形成MNI，(C)核萌发过程是细胞移除扩增的和/或多余的DNA的机制，因此是基因扩增和/或基因剂量改变的标志，(D)细胞周期检查点缺陷导致微核形成和(E)DNA的低甲基化，营养诱导或抑制DNA甲基转移酶可通过染色体丢失或染色体断裂导致微核形成。叶酸缺乏或电离辐射诱导的微核形成、核萌发和NPBS(r=0.75-0.77，P<；0.001)之间的强相关性支持了叶酸缺乏和/或电离辐射通过启动断裂-融合-桥循环而导致基因组不稳定和基因扩增的假说。在其综合模式下，CBMN检测所有细胞，包括坏死性和凋亡性细胞，以及每个细胞的核数量，以提供细胞毒性和有丝分裂活性的衡量标准。CBMN分析实际上已经发展成为一种全面测量染色体不稳定表型和由遗传缺陷和/或营养缺陷和/或外源基因毒素引起的细胞活力改变的“细胞组学”方法，从而为该方法在营养基因组学和毒素基因组学及其组合的新兴领域的应用开辟了令人兴奋的未来。皇冠版权所有(C)2006由爱思唯尔出版。保留所有权利。
The cytokinesis-block micronucleus (CBMN) assay was originally developed as an ideal system for measuring micronuclei (MNi) however it can also be used to measure nucleoplasmic bridges (NPBs), nuclear buds (NBUDs), cell death (necrosis or apoptosis) and nuclear division rate. Current evidence suggests that (a) NPBs originate from dicentric chromosomes in which the centromeres have been pulled to the opposite poles of the cell at anaphase and are therefore indicative of DNA mis-repair, chromosome rearrangement or telomere end-fusions, (b) NPBs may break to form MNi, (c) the nuclear budding process is the mechanism by which cells remove amplified and/or excess DNA and is therefore a marker of gene amplification and/or altered gene dosage, (d) cell cycle checkpoint defects result in micronucleus formation and (e) hypomethylation of DNA, induced nutritionally or by inhibition of DNA methyl transferase can lead to micronucleus formation either via chromosome loss or chromosome breakage. The strong correlation between micronucleus formation, nuclear budding and NPBs (r = 0.75-0.77, P < 0.001) induced by either folic acid deficiency or exposure to ionising radiation is supportive of the hypothesis that folic acid deficiency and/or ionising radiation cause genomic instability and gene amplification by the initiation of breakage-fusion-bridge cycles. In its comprehensive mode, the CBMN assay measures all cells including necrotic and apoptotic cells as well as number of nuclei per cell to provide a measure of cytotoxicity and mitotic activity. The CBMN assay has in fact evolved into a "cytome" method for measuring comprehensively chromosomal instability phenotype and altered cellular viability caused by genetic defects and/or nutrional deficiencies and/or exogenous genotoxins thus opening up an exciting future for the use of this methodology in the emerging fields of nutrigenomics and toxicogenomics and their combinations. Crown Copyright (c) 2006 Published by Elsevier B.V. All rights reserved.