Gene dosage mutants at adenine phosphoribosyltransferase locus induced by colcemid in Chinese hamster V79-AP4 cells

Pseudodiploid Chinese hamster V79-AP4 cells, functionally diploid at the adenine phosphoribosyltransferase (aprt)locus, were treated with colcemid, a well-known aneuploidizing agent, under various experimental conditions. Aneuploid and tetraploid cells and variants resistant to 10 g/ml of 2,6-diaminopurine (DAP), which selects for presumptive aprt^+/–heterozygotes in the untreated cells, were induced. Many of the induced variants were hypotetraploid with three (rather than four) chromosomes carrying the aprtgene. Dot-blot and Southern analysis of the DNA of these clones confirmed that they had three copies of the aprtgene. Their APRT specific enzymatic activity was 60–80% of that of wild-type V79-AP4. The results of these and other experiments suggest that in these variants resistance to DAP is due to an altered aprtgene dosage and point to a possible genetic effect of colcemid and other aneuploidizing agents in somatic mammalian cells.