Fenech Michael
CSIRO Human Nutrition, Genome Health Nutrigenomics Project, P.O. Box 10041, Adelaide BC, Adelaide, SA 5000, Australia.
Mutat Res. 2006 Aug 30;600(1-2):58-66. doi: 10.1016/j.mrfmmm.2006.05.028. Epub 2006 Jul 5.
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.
胞质分裂阻滞微核（CBMN）试验最初被开发为一种测量微核（MNi）的理想系统，然而它也可用于测量核质桥（NPBs）、核芽（NBUDs）、细胞死亡（坏死或凋亡）以及核分裂率。目前的证据表明：（a）核质桥起源于双着丝粒染色体，在后期着丝粒被拉向细胞的两极，因此指示DNA错配修复、染色体重排或端粒末端融合；（b）核质桥可能断裂形成微核；（c）核芽形成过程是细胞去除扩增和/或过量DNA的机制，因此是基因扩增和/或基因剂量改变的标志物；（d）细胞周期检查点缺陷导致微核形成；（e）营养诱导或DNA甲基转移酶抑制引起的DNA低甲基化可通过染色体丢失或染色体断裂导致微核形成。叶酸缺乏或暴露于电离辐射诱导的微核形成、核芽形成和核质桥之间的强相关性（r = 0.75 - 0.77，P < 0.001）支持了以下假设：叶酸缺乏和/或电离辐射通过启动断裂 - 融合 - 桥循环导致基因组不稳定和基因扩增。在其综合模式下，CBMN试验测量所有细胞，包括坏死和凋亡细胞以及每个细胞的核数，以提供细胞毒性和有丝分裂活性的测量。事实上CBMN试验已经演变成一种“细胞组”方法，用于全面测量由遗传缺陷和/或营养缺乏和/或外源性基因毒素引起的染色体不稳定表型和细胞活力改变，从而为该方法在营养基因组学和毒理基因组学及其组合的新兴领域中的应用开辟了令人兴奋的未来。
