Mammalian Chromosomes In Vitro. XII. Experimental Evolution of Cell Populations2

Abstract

Strain L-P59, a subline of strain L clone 929 of the mouse, had a chromosome modality of 64 to 66 with 13 or 14 metacentrics. After the population had been treated with colchicine for 48 hours, cells in the modality zone (stem cells) were greatly reduced in number. The population was predominantly occupied by high polyploids and, in the stemline zone, by genomes less frequently observed in the original population. These were considered 3s metabolically second-rate genomes. The stem cells, as expected, regained dominance after several subcultures. After prolonged colchicine treatment, the cultures either shifted completely to double-stemline numbers or changed to genomes that were rarely found in the parental population. The modality dropped to below 60, and many “monstrous” chromosomes were recorded. The double-stemline strain was apparently the result of polyploidization of the stem cells; but the rare genomes were interpreted as those that escaped colchicine poison. While all the vigorous genomes were repeatedly poisoned by colchicine whenever they entered mitosis thereby becoming giant cells which lost the ability to give rise to cell lineage, these rare genomes, due to their inferior metabolic activities, did not divide during the period of treatment, thus escaping injury. Growth assays confirmed that these cells grew much slower than the parental types. Long-term colchicine treatment on cells in vitro may be used as a method for selecting metabolically inferior mutant genomes whose isolation would be otherwise difficult.