IS MICRONUCLEUS INDUCTION BY ANEUGENS AN EARLY EVENT LEADING TO MUTAGENESIS

This study was designed to investigate a previously unidentified poten tial mechanism for mutation induction as well as to clarify a biologic al 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 treat ment. More than 85% of the micronuclei induced by each compound staine d positive for the presence of kinetochores implying that the micronuc lei contained whole chromosomes. However, these same compounds were un able 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 m utations. Thus, the induction of micronuclei containing whole chromoso mes harboring a selectable gene is not an early event leading to mutat ions in these cells.