Effect of Aminonucleoside on Serum Stimulation of Nonhistone Nuclear Protein and DNA Synthesis in Normal and SV40-transformed Human Fibroblasts

Addition of medium containing fresh serum to crowded, starved cultures of normal fibroblasts is known to induce DNA synthesis in a large proportion of the cells, preceded by stimulation of the synthesis of nonhistone chromosomal proteins. We now show that after prolonged culture, human lung fibroblasts transformed by the oncogenic virus SV40 also show a wave of DNA synthesis when exposed to fresh serum and that the synthesis of nonhistone nuclear proteins is stimulated by this treatment with the same temporal relationship to feeding and subsequent DNA synthesis as that seen in normal cells. The SV40-transformed cells differ from their normal counterparts by their resistance to the inhibitory effects of aminonucleoside. The observed rapidly occurring serum stimulation of nonhistone protein synthesis takes place in the presence of this antimetabolite, and the cells go on to synthesize DNA and divide. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of nonhistone nuclear proteins shows that the synthesis of some rapidly migrating classes of these proteins correlates with subsequent initiation of DNA synthesis.