title: G1 versus G2 cell cycle arrest after adriamycin-induced damage in mouse Swiss3T3 cells.
abstract: 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.
authors.affiliation: Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong.
authors.forename: W Y
authors.initials: WY
authors.lastname: Siu
authors.forename: C H
authors.initials: CH
authors.lastname: Yam
authors.forename: R Y
authors.initials: RY
authors.lastname: Poon
mesh_terms: D016475:3T3 Cells / Q000187:drug effects; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000633:toxicity*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D016895:Culture Media, Serum-Free; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004317:Doxorubicin / Q000494:pharmacology / Q000633:toxicity*; D016193:G1 Phase / Q000187:drug effects*; D016195:G2 Phase / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D016158:Genes, p53; D051379:Mice; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D000903:Antibiotics, Antineoplastic; C493957:Cdkn1a protein, mouse; D016895:Culture Media, Serum-Free; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D016203:CDC2 Protein Kinase