Inhibition of rat fibroblast cell proliferation at specific cell cycle stages by cocaine.
We have analyzed the role of cocaine in the control of the rat fibroblast (EL2) cell proliferation. Our data show a dose-related effect on the inhibition of DNA synthesis and cell growth when cocaine is added with serum or with a pure growth factor [Epidermal Growth Factor (EGF)]. Pretreatment by drug did not appreciably enhance the inhibition of S-phase entry above that obtained when cocaine and mitogen were added simultaneously. On the contrary, exposure of quiescent EL2 cells to cocaine has little or no effect on DNA synthesis, when drug is removed before the mitogenic stimulus. Moreover, even when cocaine is added after EGF, an exposure only within 1-8 hours is required in order to inhibit stimulation of DNA synthesis. Cocaine also suppressed the general increase in protein synthesis that occurs during the first hour after EGF addition. The combined data suggest that cocaine inhibits the traverse of mitogen-stimulated quiescent EL2 cells from Go to S phase by acting on processes that take place during the initial phase of the cell cycle.
Di Francesco
P
P
Department of Experimental Medicine and Biochemical Sciences II, University of Rome, Tor Vergata, Italy.
Pica
F
F
Favalli
C
C
Tubaro
E
E
Garaci
E
E
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D003042:Cocaine / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D011500:Protein Synthesis Inhibitors; D051381:Rats
D011500:Protein Synthesis Inhibitors; D004815:Epidermal Growth Factor; D003042:Cocaine