Changes in Cyclic Adenosine 3:5-Monophosphate Levels during Induction of Differentiation in Murine Erythroleukemia Cells

Yair Gazitt, Roberta C. Reuben, Richard A. Rifkind

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Friend virus-infected murine erythroleukemia cells were synchronized with respect to the cell cycle by the sequential exposure to thymidine and hydroxyurea. Upon release from cell cycle arrest, they go through S phase in 5 hr, G2and mitosis in 2 hr, and G1in 3 hr. Cells exposed to several inducers of erythroid differentiation, hexamethylene bisacetamide, dimethyl sulfoxide, and sodium butyrate, progress through the first synchronized cell cycle with the same kinetics as control cells but remain in the subsequent G1for as long as 6 to 8 hr. The cyclic adenosine 3:5-monophosphate (cAMP) level in synchronized control cells is high at the point of cell cycle arrest by hydroxyurea (G1-S), falls during S and G2-M, and then rises again during G1. In cells cultured with inducers, there is a transient 5 to 6-fold increase in cAMP level during mid S. Nonsynchronous cultures also display changes in cell cycle kinetics and cAMP levels when exposed to the same inducers. An increased proportion of cells in G1can be detected by 8 to 9 hr of exposure to Inducer and is recognizable for up to 10 to 20 hr, depending upon the inducer. In nonsynchronized cells a transient increase in cAMP level is observed 2 to 8 hr after addition of inducer. Several cyclic nucleotide phosphodiesterase inhibitors also elevate cAMP content, prolong the G, phase, and induce murine erythroleukemia cell differentiation. Two weaker phosphodiesterase inhibitors fail to induce differentiation.

Original languageEnglish (US)
Pages (from-to)3779-3783
Number of pages5
JournalCancer Research
Volume38
StatePublished - Nov 1 1978
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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