Iarmarcovai Gwenaëlle, Botta Alain, Orsière Thierry
Laboratoire de biogénotoxicologie et mutagenèse Environnementale (EA 1784, IFR PMSE112), Faculté de Médecine, Université de la Méditerranée, 27, bd Jean-Moulin, 13005 Marseille.
Bull Cancer. 2007 Apr;94(4):381-8.
Aneugenic compounds cause chromosome missegregation during cell division and induce aneuploidy in cells that do not die. Aneuploidy is a key step in the progression from a normal cell into a cancerous cell, and it could represent an early event in the carcinogenic process. Missegregation of chromosome during anaphase often originates from centrosome abnormality, which plays a key role in the formation of the mitotic spindle during cell division. Micronuclei (MN) are thought to be biomarkers of chromosome damage due to genetic instability or exposure to environmental mutagens or carcinogens (occupational exposure for example). The MN assay in combination with fluorescent in situ hybridization discriminates between MN containing acentric chromosome fragments (chromosome breakage) and MN containing whole chromosomes (chromosome loss), consecutively to clastogenic and aneugenic events, respectively. Centromere-positive micronuclei are due to alteration in mitotic apparatus proteins. Two pathways could be involved : chromosome migration impairment would lead to MN containing a single chromosome whereas centrosome amplification would induce MN containing several chromosomes. For biomonitoring purposes, numerous confounding factors (host factors, lifestyle, genetic polymorphism) influence the MN biomarker. Thus, the separated analysis of MN containing a single or several centromeres could be useful, as centrosome abnormalities seem to be linked with an increase in genetic instability.
非整倍体诱导化合物在细胞分裂过程中导致染色体错分离，并在未死亡的细胞中诱导非整倍体形成。非整倍体是正常细胞发展为癌细胞过程中的关键步骤，可能是致癌过程中的早期事件。后期染色体错分离通常源于中心体异常，中心体异常在细胞分裂过程中纺锤体形成中起关键作用。微核（MN）被认为是由于遗传不稳定或暴露于环境诱变剂或致癌物（如职业暴露）导致染色体损伤的生物标志物。微核试验结合荧光原位杂交可区分含有无着丝粒染色体片段的微核（染色体断裂）和含有整条染色体的微核（染色体丢失），分别对应于致断裂和非整倍体诱导事件。着丝粒阳性微核是由于有丝分裂装置蛋白的改变。可能涉及两条途径：染色体迁移受损会导致含有单条染色体的微核，而中心体扩增会诱导含有多条染色体的微核。出于生物监测目的，许多混杂因素（宿主因素、生活方式、基因多态性）会影响微核生物标志物。因此，对含有单个或多个着丝粒的微核进行单独分析可能有用，因为中心体异常似乎与遗传不稳定性增加有关。
