Malsegregation as a possible mechanism of aneuploidy induction by metal salts in MRC‐5 human cells

Abstract

Many aneugenic compounds are known to affect one or more components of the mitotic apparatus leading to an erroneous migration of chromosomes. Malsegregation occurs when a chromosome (or a chromatid) fails to migrate and remains at the metaphase plate. Nondisjunction implies the lack of dissociation between sister chromatids and the migration of both together to the same pole. The aim of the present study was to provide evidence that the aneugenic effect of some metal salts is the consequence of malsegregation at anaphase and that it is not caused by nondisjunction mechanisms. The frequencies of lagging chromosomes at anaphase‐telophase of mitosis, hypoploid metaphases, and kinetochore‐positive micronuclei induced by cadmium chloride, potassium dichromate, and cacodilic acid (dimethylarsinic acid) in MRC‐5 human cells were compared. The data indicate that all the tested compounds are able to induce aneuploidy in MRC‐5 human cells. Positive, statistically significant correlations were found when kinetochore‐positive micronuclei, hypoploidy, and lagging chromosome frequencies were compared. The results suggest that malsegregation is the main mechanism involved in the induction of aneuploidy by metal salts in MRC‐5 cells. Environ. Mol. Mutagen. 40:200–206, 2002.