Is micronucleus induction by aneugens an early event leading to mutagenesis?
This study was designed to investigate a previously unidentified potential mechanism for mutation induction as well as to clarify a biological consequence 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.
Institute of Pharmacology and Toxicology, University of Würzburg, Germany.
H
H
Stopper
I
I
Eckert
D
D
Schiffmann
D L
DL
Spencer
W J
WJ
Caspary
D000818:Animals; D003703:Demecolcine / Q000494:pharmacology; D004054:Diethylstilbestrol / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D006118:Griseofulvin / Q000494:pharmacology; D018386:Kinetochores / Q000648:ultrastructure; D007940:Leukemia L5178 / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests; D016296:Mutagenesis; D009153:Mutagens / Q000494:pharmacology*; D013937:Thymidine Kinase / Q000235:genetics; D014271:Trifluridine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D014747:Vinblastine / Q000494:pharmacology
D009153:Mutagens; D006118:Griseofulvin; D014747:Vinblastine; D004054:Diethylstilbestrol; D013937:Thymidine Kinase; D014271:Trifluridine; D003703:Demecolcine