[Changes in chromosome number, genetic instability, and occupational exposures]

Abstract

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.