Inhibition of BALB/c-3T3 cells in late G1: commitment to DNA synthesis controlled by somatomedin C.
Methylglyoxal bis-(guanylhydrazone) (mGBG) blocked the stimulation of DNA synthesis in quiescent, density-inhibited BALB/c-3T3 cells treated with platelet-derived growth factor (PDGF) and platelet-poor plasma (PPP). Competence formation produced by a transient exposure to PDGF was not effected by mGBG. In contrast, mGBG effectively inhibited the PPP-stimulated progression of competent cells through the G1 phase of the cell cycle, although maximal inhibition was observed when mGBG was present during both the exposure to PDGF- and PPP-supplemented media. When quiescent cells were treated with PDGF and PPP-supplemented media in the presence of mGBG for 12--18 hours and the mGBG was then removed, cells entered the S phase after a 4 hour lag. The rate of entry into the S phase, but not the time necessary for the cells to progress from the mGBG block into the S phase, was dependent on the concentration of PPP present after removal of the mGBG. Either somatomedin C or insulin, but not epidermal growth factor, fibroblast growth factor, or PDGF were able to substitute for PPP in allowing cells to enter the S phase after the cells were released from the mGBG block. A marked inhibition of (3H)-leucine incorporation in serum-stimulated cultures was produced at mGBG concentrations which caused no decrease in the amount of (3H)-uridine incorporated during a short (15 minute) pulse. The ability of hormones to allow cells to progress to the late G1 phase and become committed to DNA synthesis after a mGBG inhibition was not related to their ability to restore the normal rate of protein synthesis as determined by (3H)-leucine incorporation.
D000818:Animals; D002455:Cell Division; D002999:Clone Cells / Q000166:cytology; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I; D007399:Interphase / Q000187:drug effects*; D007930:Leucine / Q000378:metabolism; D008935:Mitoguazone / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor; D013002:Somatomedins / Q000494:pharmacology*
D006133:Growth Substances; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D004247:DNA; D007930:Leucine; D008935:Mitoguazone