Cell cycle specificity and reversibility of the inhibitory effect of epidermal G1-chalone on DNA synthesis in partially synchronized RTE-2 keratinocytes in vitro.
The specific action of a pig skin fraction enriched in epidermal G1-chalone, a tissue-specific inhibitor of epidermal DNA synthesis, was investigated by means of flow cytofluorometry. The results indicate that G1-chalone inhibits progression of partially synchronized rat tongue epithelial cells (line RTE-2) through the cell cycle at a point 2 h prior to the beginning of the S-phase. Approximately 8 h after chalone addition, the cells can overcome the inhibition and begin to enter the S-phase. The duration of this delay is concentration-independent, but the fraction of cells affected is proportional to the chalone concentration. The progression of cells which already have entered S-phase is not affected. In contrast to the G1-chalone preparation, aphidicolin, a potent inhibitor of DNA polymerase alpha, clearly shows S-phase-specific inhibition. These results indicate that the epidermal G1-chalone inhibits epidermal cell proliferation in a fully reversible manner by a highly specific effect on cell cycle traverse.
Tiegel
A
A
Deutsches Krebsforschungszentrum (German Cancer Research Center), Institut für Biochemie, Heidelberg, Federal Republic of Germany.
Richter
K H
KH
Marks
F
F
D000818:Animals; D016590:Aphidicolin; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects*; D004224:Diterpenes / Q000494:pharmacology; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects; D004848:Epithelium; D005434:Flow Cytometry; D006131:Growth Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D051381:Rats; D014059:Tongue
D004224:Diterpenes; D006131:Growth Inhibitors; D016590:Aphidicolin