Preston R J
Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709, USA.
Environ Mol Mutagen. 1996;28(3):176-81. doi: 10.1002/(SICI)1098-2280(1996)28:3<176::AID-EM3>3.0.CO;2-C.
The task of the Workgroup on "Disruption of Chromosome Mover Components" was to establish what cellular structures are involved in chromosome segregation and how disruption of these could occur. Recent research on the mechanism of action of the cellular components that segregate chromosomes accurately during mitosis or meiosis has served to highlight the number of potential targets for disruption. The process of chromosome segregation represents an orchestrated chain of events centered on the activities of cellular motors, kinesins and dyneins. These motors are involved in arranging chromosomes at the metaphase plate, providing the spindle tension necessary for progression, and the actual segregation of the chromosomes to the poles. The Workgroup determined that there is a lack of information on the effects of chemical exposure to cell motors and other chromosome mover components, and that there is a clear need for further research. This article describes the discussions of the Workgroup and highlights areas of future research into chromosome movement, particularly in human meiotic and mitotic cells. The Workgroup emphasized that obtaining mechanistic data on the induction of aneuploidy will allow for extrapolation of the dose response curves for chemical exposures below the level of observation and for using aneuploidy data for quantitative risk assessment for adverse health effects.
“染色体移动成分破坏”工作组的任务是确定哪些细胞结构参与染色体分离以及这些结构如何被破坏。最近关于在有丝分裂或减数分裂期间精确分离染色体的细胞成分作用机制的研究,突显了可能被破坏的靶点数量。染色体分离过程是一系列精心编排的事件,其核心是细胞马达蛋白(驱动蛋白和动力蛋白)的活动。这些马达蛋白参与将染色体排列在中期板上,提供前进所需的纺锤体张力,并将染色体实际分离到两极。工作组确定,关于化学物质暴露对细胞马达蛋白和其他染色体移动成分的影响缺乏相关信息,显然需要进一步研究。本文描述了工作组的讨论内容,并着重指出了未来关于染色体移动的研究领域,特别是在人类减数分裂和有丝分裂细胞方面。工作组强调,获取关于非整倍体诱导的机制数据,将有助于外推低于观察水平的化学物质暴露剂量反应曲线,并利用非整倍体数据进行不良健康影响的定量风险评估。