Tumorigenicity of Friend murine erythroleukemia cell lines differing in spontaneous differentiation rates

The relationship between tumorigenicity and in vitro differentiation was studied in four Friend erythroleukemia cell lines. The cell lines were isolated by repeated subcloning of an unmutagenized population (sib selection). The cell lines differed in their ability to form tumors when 10(3) cells were injected subcutaneously into syngeneic mice (8 to 56% animals with tumors). The ability of cell lines to form tumors was not proportional to their ability to be induced to differentiate by dimethylsulfoxide. The cell lines had indistinguishable chromosome numbers, plating efficiencies, number of cycling cells, population doubling times and spontaneous mutation rates to drug resistance. However, the cell lines had different spontaneous differentiation rates in the absence of dimethylsulfoxide (0.87 to 16.0 X 10(-4) per cell per generation). The ability of cell lines to form tumors was inversely proportional to their spontaneous differentiation rate. Apparently cells which are most efficiently blocked in differentiation have the highest probability of forming tumors.