Microsatellite instability is co-selectable with gene amplification in a mammalian mutator phenotype

The effect of an unbalanced nucleotide pool on the stability of dinucleotid e (CA)n microsatellite sequences was investigated in the mutator phenotype CSA7 clone isolated from Chinese hamster CHEF18 cell line. A series of clon es isolated from CHEF18 and CSA7 cells and resistant to 6-thioguanine (TG) were shown to be stable at the three examined microsatellite loci. Furtherm ore, the clones isolated fi om CHEF18 cells and resistant to N-phosphonacet yl-L-aspartate (PALA) were stable, whereas those isolated from CSA7 clone w ere unstable. At the biological level the clones with instability did not s how tolerance of methylnitrosourea-induced damage, thus excluding the prese nce of a defective mismatch repair On the contrary, the molecular character ization showed that the instability, measured as extension or contraction o f (CA)(n) repeats, involved numerous repeats resembling the amplification r ather than mutation of the microsatellite loci. The results therefore indic ate that the unbalanced nucleotide pool of CSA7 clone influences the overal l rate of gene amplification and support that the unstable microsatellites are coselectable with other gene amplification events.