title: Micronuclei containing whole chromosomes harbouring the selectable gene do not lead to mutagenesis.
abstract: Loss of heterozygosity is one genetic change observed in many tumours. We do not know whether the loss of chromosomal material through micronucleus formation is a viable mechanism associated with, and possibly leading to, genetic disease. Previously, we treated L5178Y mouse lymphoma cells with four aneugens. Although these aneugens induced micronuclei containing predominantly whole chromosomes, they did not induce mutations at Tk1, the selectable gene, under the same non-toxic conditions in which they induced micronuclei. This suggested that the induction of micronuclei containing whole chromosomes was not an early event leading to phenotypically expressed mutations in these cells under the conditions used. However, it is possible that chromosome 11, on which Tk1 resides, may be under-represented in the micronucleus population. To find out the frequency of induction of micronuclei containing chromosome 11, we applied fluorescence in situ hybridization using a chromosome 11 paint to micronuclei induced by colcemid and vinblastine. We found that the numbers of micronuclei containing chromosome 11 are more than sufficient to be detectable as mutations if these micronuclei lead to viable mutants. We conclude that the formation of micronuclei containing whole chromosomes does not lead to viable, dividing mutants in this system.
authors.affiliation: Department of Toxicology, University of Würzburg, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Eckert
authors.forename: W J
authors.initials: WJ
authors.lastname: Caspary
authors.forename: M
authors.initials: M
authors.lastname: Nüsse
authors.forename: M
authors.initials: M
authors.lastname: Liechty
authors.forename: L
authors.initials: L
authors.lastname: Davis
authors.forename: H
authors.initials: H
authors.lastname: Stopper
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D003703:Demecolcine / Q000633:toxicity*; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007940:Leukemia L5178; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity; D013937:Thymidine Kinase / Q000235:genetics; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000633:toxicity*
chemical_list: D009153:Mutagens; D014747:Vinblastine; D013937:Thymidine Kinase; D003703:Demecolcine