Identification of aneuploidy‐inducing agents using cytokinesis‐blocked human lymphocytes and an antikinetochore antibody

Abstract

The identification of agents causing aneuploidy in humans, a condition associated with carcinogenesis and birth defects, is currently limited due to the highly skilled and time‐consuming nature of cytogenetic analyses. We report the development of a new simple and rapid assay to identify aneuploidy‐inducing agents (aneuploidogens). The assay involves the chemical‐ or radiation‐induced formation of micronuclei in cytokinesis‐blocked human lymphocytes and the use of an antikinetochore antibody to determine whether the micronuclei contain centromeres—a condition indicating a high potential for aneuploidy. All agents tested produced dose‐related increases in the frequency of micronucleated cells. The micronucleated cells induced by the known aneuploidogens—colchicine, vincristine sulfate, and diethylstilbestrol—contained kinetochore‐positive micronuclei 92, 87, and 76% of the time, respectively. In contrast, the micronucleated cells induced by the potent clastogens—ionizing radiation and sodium arsenite—contained kinetochore‐positive micronuclei only 3 and 19% of the time, respectively. These results indicate that this relatively simple assay can discriminate between aneuploidogens and clastogens and may allow a more rapid identification of environmental and therapeutic agents with aneuploidy‐inducing potential.