Fenech Michael, Holland Nina, Zeiger Errol, Chang Peter Wushou, Kirsch-Volders Micheline, Bolognesi Claudia, Stopper Helga, Knudsen Lisbeth E, Knasmueller Siegfried, Nersesyan Armen, Thomas Philip, Dhillon Varinderpal, Deo Permal, Franzke Bernhard, Andreassi Maria-Grazia, Laffon Blanca, Wagner Karl-Heinz, Norppa Hannu, da Silva Juliana, Volpi Emanuela V, Wilkins Ruth, Bonassi Stefano
Health and Biomedical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide 5000, Australia; Genome Health Foundation, North Brighton, SA 5048, Australia.
Center for Environmental Research and Community Health (CERCH), University of California, Berkeley, Berkeley, CA, USA.
Mutat Res Rev Mutat Res. 2024 Jul-Dec;794:108511. doi: 10.1016/j.mrrev.2024.108511. Epub 2024 Sep 2.
Micronuclei (MN) are a nuclear abnormality that occurs when chromosome fragments or whole chromosomes are not properly segregated during mitosis and consequently are excluded from the main nuclei and wrapped within nuclear membrane to form small nuclei. This maldistribution of genetic material leads to abnormal cellular genomes which may increase risk of developmental defects, cancers, and accelerated aging. Despite the potential importance of MN as biomarkers of genotoxicity, very little was known about the optimal way to measure MN in humans, the normal ranges of values of MN in healthy humans and the prospective association of MN with developmental and degenerative diseases prior to the 1980's. In the early 1980's two important methods to measure MN in humans were developed namely, the cytokinesis-block MN (CBMN) assay using peripheral blood lymphocytes and the Buccal MN assay that measures MN in epithelial cells from the oral mucosa. These discoveries greatly increased interest to use MN assays in human studies. In 1997 the Human Micronucleus (HUMN) project was founded to initiate an international collaboration to (i) harmonise and standardise the techniques used to perform the lymphocyte CBMN assay and the Buccal MN assay; (ii) establish and collate databases of MN frequency in human populations world-wide which also captured demographic, lifestyle and environmental genotoxin exposure data and (iii) use these data to identify the most important variables affecting MN frequency and to also determine whether MN predict disease risk. In this paper we briefly describe the achievements of the HUMN project during the period from the date of its foundation on 9th September 1997 until its 26th Anniversary in 2023, which included more than 200 publications and 23 workshops world-wide.
微核(MN)是一种核异常现象,当染色体片段或整条染色体在有丝分裂过程中未正确分离,从而被排除在主核之外,并被核膜包裹形成小核时就会出现。这种遗传物质的错误分配会导致细胞基因组异常,可能增加发育缺陷、癌症和加速衰老的风险。尽管微核作为遗传毒性生物标志物具有潜在重要性,但在20世纪80年代之前,人们对测量人类微核的最佳方法、健康人群微核的正常数值范围以及微核与发育和退行性疾病的前瞻性关联知之甚少。20世纪80年代初,开发了两种测量人类微核的重要方法,即使用外周血淋巴细胞的胞质分裂阻滞微核(CBMN)试验和测量口腔黏膜上皮细胞微核的颊黏膜微核试验。这些发现极大地增加了在人体研究中使用微核试验的兴趣。1997年,人类微核(HUMN)项目成立,旨在发起一项国际合作,以(i)协调和标准化用于进行淋巴细胞CBMN试验和颊黏膜微核试验的技术;(ii)建立和整理全球人群微核频率数据库,该数据库还收集了人口统计学、生活方式和环境遗传毒素暴露数据;(iii)利用这些数据确定影响微核频率的最重要变量,并确定微核是否可预测疾病风险。在本文中,我们简要描述了HUMN项目从1997年9月9日成立至2023年26周年期间所取得的成就,其中包括全球范围内200多篇出版物和23次研讨会。