Phenotypic Reversion of Cultured Mouse Adenocarcinoma Cells: Mediation by Cell Density and Chemical Exposure

Abstract

Reversions of mouse adenocarcinoma (MAC/10T3) cells from fibroblastic, high-tumorigenic to epithelioid, low-tumorigenic phenotype was obtained by either seeding MAC/10T3 cells at low cell density or by exposing them to varying concentrations of IQ-1 or IQ-2 compounds. Clonal isolation was carried out by the ring isolation technique, and the various cloned revertant types were characterized by their cell morphology, saturation density, and tumorigenicity. Most of the revertants isolated 11 to 15 days after seeding at low cell density eventually returned to the fibroblastic, high-tumorigenic (HT) phenotype when serially passed at high cell density. In contrast, 25 to 36.3% of the slow-growing revertants isolated between 21 and 28 days after seeding at low cell density maintained the parental epithelioid morphology when subsequently seeded at high cell density. The observation of a possible temporal relationship between the low density seeding and the occurrence of stable revertants, and the observed differential cellular proliferation at low or high cell density, may suggest that reversion from a less tumorigenic phenotype to a highly tumorigenic state may involve a multistep process with a stringent requirement for active cell cycle.