Induction of DNA synthesis in BALB/c 3T3 cells by serum components: reevaluation of the commitment process.
Serum contains a growth factor derived from platelets and also growth factors derived from platelet-poor plasma. Extracts of heated (100 degrees ) human platelets function synergistically with platelet-poor plasma to induce DNA synthesis in quiescent, density-inhibited BALB/c 3T3 cells. Platelet-poor plasma alone did not induce DNA synthesis. Cells exposed to platelet extracts became competent to enter the cell cycle, but the rate of entry into the S phase depended upon the concentration of platelet-poor plasma. The time required for the induction of this competent state was a function of the concentration of the platelet extract. A 2-hr exposure to 100 mug of the platelet extract at 37 degrees caused the entire cell population to become competent to enter the S phase. At 4 degrees or 25 degrees the cells did not become competent to synthesize DNA. The platelet extract-induced competent state was stable for at least 13 hr after removal of the platelet extract; however, in the absence of platelet-poor plasma, these competent cells did not progress through the cell cycle. The addition of an optimal concentration of platelet-poor plasma (5%) to these competent cells initiated cell cycle traverse with a rapid, first-order entry of cells into the S phase beginning 12 hr after addition of the plasma. The addition of a suboptimal concentration of the plasma (0.25%) did not increase the rate of cell entry into the S phase. Thus, the induction of DNA synthesis in quiescent BALB/c 3T3 cells can be resolved into at least two phases, controlled by different serum components: (i) competence, induced by the platelet-derived growth factor; and (ii) progression of competent cells into the cell cycle, mediated by factors in platelet-poor plasma.
D000818:Animals; D001790:Blood Physiological Phenomena; D001792:Blood Platelets / Q000502:physiology; D002453:Cell Cycle; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D006133:Growth Substances / Q000097:blood / Q000502:physiology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010949:Plasma / Q000502:physiology; D013268:Stimulation, Chemical; D014020:Tissue Extracts / Q000494:pharmacology
D006133:Growth Substances; D014020:Tissue Extracts; D004247:DNA
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