Germanium oxide inhibits the transition from G2 to M phase of CHO cells.
We report here for the first time that germanium oxide (GeO(2)) blocks cell progression. GeO(2) is not genotoxic to Chinese hamster ovary (CHO) cells and has limited cytotoxicity. However, GeO(2) arrests cells at G2/M phase. The proportion of cells stopped at G2/M phase increased dose-dependently up to 5 mM GeO(2) when treated for 12 h, but decreased at GeO(2) concentration was greater than 5 mM. Analysis of 5-bromodeoxyuridine-labeled cells indicated that GeO(2) delayed S phase progression in a dose-dependent manner, and blocked cells at G2/M phase. Microscopic examination confirmed that GeO(2) treatment arrested cells at G2 phase. Similar to several other events that cause G2 block, the GeO(2)-induced G2 block can also be ameliorated by caffeine in a dose- and time-dependent manner. To explore the mechanism of G2 arrest by GeO(2), cyclin content and cyclin-dependent kinase activity were examined. Cyclin B1 level was not affected after GeO(2) treatment in CHO cells. However, GeO(2) decreased p34(cdc2) kinase (Cdk1) activity. The kinase activity recovered within 9 h after GeO(2) removal and correlated with the transition of G2/M-G1 phase of the cells. This result suggests that GeO(2) treatment reduces Cdk1 activity and causing the G2 arrest in CHO cells.
Chiu
Shu Jun
SJ
Institute of Radiation Biology and Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan, ROC.
Lee
Ming Yao
MY
Chen
Hsiao Wei
HW
Chou
Wen Gang
WG
Lin
Lih Yuan
LY
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D016466:CHO Cells; D002453:Cell Cycle / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology; D006224:Cricetinae; D016213:Cyclins / Q000378:metabolism; D003603:Cytotoxins / Q000494:pharmacology / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016195:G2 Phase / Q000187:drug effects*; D005857:Germanium / Q000494:pharmacology / Q000633:toxicity*; D015151:Immunoblotting; D015162:Micronucleus Tests; D008938:Mitosis / Q000187:drug effects*; D013997:Time Factors
D016213:Cyclins; D003603:Cytotoxins; D005857:Germanium; C040516:germanium oxide; D016203:CDC2 Protein Kinase; D003078:Colchicine