Identification of aneuploidy-inducing agents using cytokinesis-blocked human lymphocytes and an antikinetochore antibody.
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.
Biomedical Sciences Division, Lawrence Livermore National Laboratory, Livermore, CA 94550.
D A
DA
Eastmond
J D
JD
Tucker
D000782:Aneuploidy; D000974:Antibodies, Antinuclear; D001151:Arsenic / Q000494:pharmacology; D018053:Arsenites; D002455:Cell Division / Q000187:drug effects; D002503:Centromere / Q000276:immunology*; D002588:Cesium Radioisotopes; D002875:Chromosomes / Q000276:immunology*; D003078:Colchicine / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D004054:Diethylstilbestrol / Q000494:pharmacology; D008214:Lymphocytes; D015162:Micronucleus Tests; D009153:Mutagens; D017670:Sodium Compounds; D014750:Vincristine / Q000494:pharmacology
D000974:Antibodies, Antinuclear; D018053:Arsenites; D002588:Cesium Radioisotopes; D009153:Mutagens; D017670:Sodium Compounds; D003571:Cytochalasin B; C017947:sodium arsenite; D014750:Vincristine; D004054:Diethylstilbestrol; D001151:Arsenic; D003078:Colchicine