Aneugenicity

Aneugenicity is the property of certain chemicals, physical agents, or biological factors to induce aneuploidy, an abnormal number of chromosomes in daughter cells, by interfering with the mitotic spindle, kinetochore–microtubule attachments, or centrosome function. It is a specific form of genotoxicity focused on chromosomal number rather than structural damage to chromosomes.

Aneugens differ from clastogens, which cause structural chromosomal alterations such as breaks and rearrangements. Aneugenic effects arise mainly during mitosis when chromosomes fail to segregate properly, leading to daughter cells with gain or loss of entire chromosomes. Mechanisms include disruption of spindle assembly or dynamics, improper kinetochore attachment, formation of multipolar or defective spindles, and centrosome amplification. Resulting mis-segregation can produce lagging chromosomes and micronuclei, contributing to cellular aneuploidy, mosaicism, and potential implications for development or cancer.

Common examples of aneugens include microtubule-targeting agents such as colchicine, vinblastine, vincristine, and taxanes, which perturb spindle function. Certain metals and industrial chemicals, as well as some environmental and occupational exposures, have also been associated with aneugenic effects in experimental settings. The relevance of aneugenicity to disease is particularly noted in cancer, where aneuploidy is a frequent feature, as well as in developmental toxicology, where chromosome number changes can have profound effects.

Detection and assessment typically rely on cytogenetic methods. Micronucleus assays, often combined with centromere or kinetochore staining (for example, CREST-based methods), help distinguish aneugenic (centromere-positive) from clastogenic (centromere-negative) events. Regulatory testing may include in vitro and in vivo micronucleus studies to evaluate aneugenic potential. See also genotoxicity, mutagenicity, and chromosomal instability.