Genetic Method to Quantitate Induced Chromosome Breaks Using a Mouse/Human Monochromosomal Hybrid Cell Line: Identification of Potential Clastogenic Agents

摘要

Micronuclei induction in bone marrow erythrocytes of mice is a commonly used index of clastogenicity. However, micronuclei could also originate from intact lagging chromosomes. We have used antikinetochore antibodies to distinguish kinetochore containing micronuclei from those originating from acentric chromosomal fragments. This provides a method to identify the agents capable of inducing lagging chromosomes, by inference aneuploidy in an in vivo system. The technique was evaluated using a known clastogen, ionizing radiation; and a known aneuploidy inducing agent, vincristine sulfate. The frequence of total micronucleated erythrocytes increased with the dose with both agents. Micronuclei induced by x-irradiation were predominantly negative for kinetochores while the majority of the micronuclei resulting from the effect of Vincristine contained kinetochore. Staining for kinetochores provide a qualitative method to identify environmental agents capable of inducing aneuploidy.