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

Journal Article · Sun Jan 01 04:00:00 EST 1989 · Environ. Mol. Mutagen.; (United States)

DOI:https://doi.org/10.1002/em.2850130104· OSTI ID:6497170

Eastmond, D A; Tucker, J D

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.

• Research Organization: Lawrence Livermore National Lab., Livermore, CA (USA)
• OSTI ID: 6497170
• Journal Information: Environ. Mol. Mutagen.; (United States), Journal Name: Environ. Mol. Mutagen.; (United States) Vol. 13:1; ISSN EMMUE
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALOIDS
ANEUPLOIDY
ANIMAL CELLS
ANIMALS
ANTIBODIES
ANTIMITOTIC DRUGS
ANTIPYRETICS
ARSENIC
BIOASSAY
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL CONSTITUENTS
CELL DIVISION
CELL NUCLEI
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHROMOSOMES
COLCHICINE
CONNECTIVE TISSUE CELLS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELEMENTS
IONIZING RADIATIONS
LEUKOCYTES
LYMPHOCYTES
MAMMALS
MAN
MATERIALS
MUTAGENS
ORGANIC COMPOUNDS
PLOIDY
PRIMATES
RADIATIONS
SEMIMETALS
SOMATIC CELLS
VERTEBRATES