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Mutagenesis vol. 9 no. 5 pp. 411-416, 1994
© 1994 UK Environmental Mutagen Society/Oxford University Press

research-article

Is micronucleus induction by aneugens an early event leading to mutagenesis?

Helga Stopper1,4, Inge Eckert1, Dietmar Schiffmann2, Diane L. Spencer3 and William J. Caspary3

1Institute of Pharmacology and Toxicology, University of Würzburg 97078 Wurzburg 2Institute of Animal Physiology, University of Rostock 18051 Rostock, Germany 3Germany and Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institutes of Health Research Triangle Park, NC 27709, USA

This study was designed to investigate a previously unidentified potential mechanism for mutation induction as well as to clarify a biological consequence of micronucleus formation. We compared the induction of micronuclei with mutation induction as measured by trifluorothymidine (TFT) resistance in mouse L5178Y cells using four aneugens: colcemid, diethylstilbestrol, griseofulvin and vinblastine. All four compounds induced micronuclei which appeared in the first cell cycle after treatment. More than 85% of the micronuclei induced by each compound stained positive for the presence of kinetochores implying that the micronuclei contained whole chromosomes. However, these same compounds were unable to induce TFT resistance under three different treatment regimes. We concluded that these compounds, under conditions where they induce primarily kinetochore positive micronuclei, were not able to induce mutations. Thus, the induction of micronuclei containing whole chromosomes harboring a selectable gene is not an early event leading to mutations in these cells.

4To whom correspondence should be addressed


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