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Effects of withdrawal of a mitogenic stimulus on progression of fibroblasts into S phase: Differences between serum and purified multiplication‐stimulating activity
Author(s) -
Bolen Joe B.,
Smith Gary L.
Publication year - 1977
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1040910314
Subject(s) - dna synthesis , cell cycle , mitosis , thymidine , fibroblast , cell division , biology , stimulation , microbiology and biotechnology , dna replication , embryo , cell culture , dna , cell , biochemistry , endocrinology , genetics
Multiplication‐stimulating activity (MSA) for chicken embryo fibroblasts was purified from serum‐free medium conditioned by the growth of a rat liver cell line. A comparison between calf serum and purified MSA was made regarding the regulation of the fibroblast cell cycle. Addition of serum or MSA to stationary, quiescent cells stimulates them to enter the DNA synthetic phase after a characteristic lag period. Exposure to serum for shorter periods of time will irreverisbly commit cells to continue through the cell cycle and initiate DNA replication in the absence of serum. In contrast, the withdrawal of purified MSA from the medium results in an abrupt halt in the progression of cells towards S phase. The results of labeled thymidine incorporation and autoradiographic experiments clearly indicate that the point at which cells become irreversibly committed to enter the DNA synthetic period is at or near the G 1 ‐S boundary. The abrupt decay of the stimulation upon withdrawal of purified MSA provides a unique opportunity to investigate the biochemistry of this discrete phase of the cell cycle.