Phenotypic variability of cultured rat hepatoma cell population in respect to alpha‐fetoprotein synthesis

McA-RH 7777 hepatoma cells were cloned on 2 occasions a week apart (test cloning). Alpha-fetoprotein (AFP) phenotypes of primary and secondary clones from 55 primary clones were estimated. High interclonal heterogeneity of AFP expression was demonstrated. This variability exceeded by several orders of magnitude the mutation rate. We also found intraclonal differences in rates of variability. A "stabilizing" cloning was also carried out, aiming at the selection of AFP+ and AFP- stable cell lines. Stabilizing cloning included 7 cycles of cloning and selection of the most phenotypically stable clone. This stability was shown to be incomplete during the maintenance of clones in culture.