The in vitro micronucleus test: a multi-endpoint assay to detect simultaneously mitotic delay, apoptosis, chromosome breakage, chromosome loss and non-disjunction

Abstract

Genotoxicity testing aims to detect a large range of genetic damage endpoints and evaluate such results in context of cell survival. The cytokinesis block micronucleus test offers the advantage to provide simultaneously information on both cell cycle progression and chromosome/genome mutations. Indeed, 1. frequencies of cytokinesis-blocked binucleated cells (and polynucleated) are good estimators of the mitotic rate; 2. frequencies of apoptotic figures in mononucleated and binucleated cells provide a measure for cell death before or after cell division; 3. combination of fluorescence in situ hybridization (FISH) for centromere/telomeres and micronucleus scoring allows discrimination between clastogenic and aneugenic events; 4. detection of FISH signals for chromosome specific sequences in both macronuclei and micronuclei, discriminates between aneuploidy due to chromosome non-disjunction or to chromosome loss. The cytokinesis block in vitro micronucleus test is thus a cytogenetic multi-test providing mechanistic information with a simple, rapid, objective, microscopical analysis.