Terminal differentiation of human erythroleukemia cell line K562 induced by aphidicolin.
To analyze the relationship between differentiation and DNA replication, the effect of aphidicolin, a specific inhibitor for DNA polymerase alpha, was measured with respect to erythroid differentiation and activities of DNA polymerases alpha, beta, and gamma. Five micromolar aphidicolin completely blocked the growth of K562 cells and caused 80% of cells to become hemoglobin positive after 5 days exposure. The cessation of K562 cell growth induced by aphidicolin was irreversible, whereas the inhibition of HeLa cell growth was completely reversible. The enzyme activity of DNA polymerase alpha of K562 cells showed a 50-110% increase with aphidicolin treatment as compared to control K562 cells; activities of DNA polymerases beta and gamma were not affected. These features sharply contrasted with the erythroid induction of the same cells by hemin, where cell growth was not suppressed and DNA polymerase alpha was not increased but rather decreased. The enzyme activity of DNA polymerase alpha remained high even after removal of aphidicolin from the culture medium. These results suggest that treatment with aphidicolin might induce an accumulation of protein factors for replication and/or differentiation, causing rapid cell differentiation of cells without cell division.
Murate
T
T
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Kagami
Y
Y
Hotta
T
T
Yoshida
T
T
Saito
H
H
Yoshida
S
S
D000970:Antineoplastic Agents / Q000494:pharmacology; D016590:Aphidicolin; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors*; D004261:DNA Replication / Q000187:drug effects; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects*; D006367:HeLa Cells; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D000970:Antineoplastic Agents; D004224:Diterpenes; D016590:Aphidicolin; D004257:DNA Polymerase II; D004259:DNA-Directed DNA Polymerase