G1 versus G2 cell cycle arrest after adriamycin-induced damage in mouse Swiss3T3 cells

FEBS Lett. 1999 Nov 19;461(3):299-305. doi: 10.1016/s0014-5793(99)01481-7.


Cell cycle arrest after different types of DNA damage can occur in either G1 phase or G2 phase of the cell cycle, involving the distinct mechanisms of p53/p21(Cip1/Waf1) induction, and phosphorylation of Cdc2, respectively. Treatment of asynchronously growing Swiss3T3 cells with the chemotherapeutic drug adriamycin induced a predominantly G2 cell cycle arrest. Here we investigate why Swiss3T3 cells were arrested in G2 phase and not in G1 phase after adriamycin-induced damage. We show that adriamycin was capable of inducing a G1 cell cycle arrest, both during the G0-G1 transition and during the G1 phase of the normal cell cycle. In G0 cells, adriamycin induced a prolonged cell cycle arrest. However, adriamycin caused only a transient cell cycle delay when added to cells at later time points during G0-G1 transition or at the G1 phase of normal cell cycle. The G1 arrest correlated with the induction of p53 and p21(Cip1/Waf1), and the exit from the arrest correlated with the decline of their expression. In contrast to the G1 arrest, adriamycin-induced G2 arrest was relatively tight and correlated with the Thr-14/Tyr-15 phosphorylation of cyclin B-Cdc2 complexes. The relative stringency of the G1 versus G2 cell cycle arrest may explain the predominance of G2 arrest after adriamycin treatment in mammalian cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells / drug effects
  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • Antibiotics, Antineoplastic / toxicity*
  • CDC2 Protein Kinase / metabolism
  • Cell Division / drug effects
  • Culture Media, Serum-Free
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / biosynthesis
  • Cyclins / genetics
  • Cyclins / metabolism
  • DNA Damage
  • Doxorubicin / pharmacology
  • Doxorubicin / toxicity*
  • G1 Phase / drug effects*
  • G2 Phase / drug effects*
  • Gene Expression Regulation / drug effects
  • Genes, p53
  • Mice
  • Resting Phase, Cell Cycle / drug effects
  • Tumor Suppressor Protein p53 / biosynthesis


  • Antibiotics, Antineoplastic
  • Cdkn1a protein, mouse
  • Culture Media, Serum-Free
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Tumor Suppressor Protein p53
  • Doxorubicin
  • CDC2 Protein Kinase