MICRONUCLEI CONTAINING WHOLE CHROMOSOMES HARBORING THE SELECTABLE GENE DO NOT LEAD TO MUTAGENESIS

Loss of heterozygosity is one genetic change observed in many tumours, We do not know whether the loss of chromosomal material through micro nucleus formation is a viable mechanism associated with, and possibly leading to, genetic disease, Previously, we treated L5178Y mouse lymph oma cells with four aneugens, Although these aneugens induced micronuc lei containing predominantly whole chromosomes, they did not induce mu tations at Tk1, the selectable gene, under the same non-toxic conditio ns in which they induced micronuclei, This suggested that the inductio n of micronuclei containing whole chromosomes was not an early event l eading 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 chrom osome 11, we applied fluorescence in situ hybridization using a chromo some 11 paint to micronuclei induced by colcemid and vinblastine, We f ound that the numbers of micronuclei containing chromosome 11 are more than sufficient to be detectable as mutations if these micronuclei le ad to viable mutants, We conclude that the formation of micronuclei co ntaining whole chromosomes does not lead to viable, dividing mutants i n this system.