ABSTRACT
Lysosomal inhibitors (amino acid methyl esters) and the platelet-derived growth factor stimulate the resting NIH 3T3 cells to enter the S period. Incubation of cells in the medium containing lysosomal inhibitors enhances protein accumulation and seemingly does not disrupt lysosomes. These results indicate that proliferative homeostasis depends on the metabolic status of cells and that catabolic processes activated in resting cells negatively influence the prereplicative reactions.
Subject(s)
Fibroblasts/drug effects , Lysosomes/drug effects , Animals , Cell Division/drug effects , Cell Line , Cells, Cultured/drug effects , Cells, Cultured/ultrastructure , Depression, Chemical , Fibroblasts/ultrastructure , Isoleucine/analogs & derivatives , Isoleucine/pharmacology , Lysosomes/ultrastructure , Methionine/analogs & derivatives , Methionine/pharmacology , Mice , Platelet-Derived Growth Factor/pharmacology , S Phase/drug effectsSubject(s)
DNA/biosynthesis , Epidermal Growth Factor/pharmacology , Platelet-Derived Growth Factor/pharmacology , Protein Synthesis Inhibitors/pharmacology , Animals , Cell Line , Cycloheximide/pharmacology , Fibroblasts/drug effects , Fibroblasts/metabolism , Interphase/drug effects , Mice , Puromycin/pharmacologyABSTRACT
NIH 3T3 mouse fibroblasts cultured in the medium containing 0.5% serum for 2, 4, 8, 24, 48 and 72 hours were fused to cells stimulated for proliferation by replacing the medium with a fresh one containing 10% serum; DNA synthesis was studied in monokaryons, homo- and heterodikaryons using radioautography and double-labelling technique. Cells that were cultured in the medium with a low serum content for 72 hours exerted their inhibitory effect on the entry of stimulated nuclei into the S period in heterodikaryons, whereas cells deprived of serum for shorter periods failed to exert this effect. It thus appears that in cell fusion studies with NIH 3T3 cells, the effects of endogenous growth inhibitor(s) produced by resting cells may be revealed not earlier than by the 3rd day of serum depletion.