Germanium oxide inhibits the transition from G2 to M phase of CHO cells

We report here for the first time that germanium oxide (GeO2) blocks cell progression. GeO2 is not genotoxic to Chinese hamster ovary (CHO) cells and has limited cytotoxicity. However, GeO2 arrests cells at G2/M phase. The proportion of cells stopped at G2/M phase increased dose-dependently up to 5 mM GeO2 when treated for 12 h, but decreased at GeO2 concentration was greater than 5 mM. Analysis of 5-bromodeoxyuridine-labeled cells indicated that GeO2 delayed S phase progression in a dose-dependent manner, and blocked cells at G2/M phase. Microscopic examination confirmed that GeO2 treatment arrested cells at G2 phase. Similar to several other events that cause G2 block, the GeO2-induced G2 block can also be ameliorated by caffeine in a dose- and time-dependent manner. To explore the mechanism of G2 arrest by GeO2, cyclin content and cyclin-dependent kinase activity were examined. Cyclin B1 level was not affected after GeO2 treatment in CHO cells. However, GeO2 decreased p34cdc2 kinase (Cdk1) activity. The kinase activity recovered within 9 h after GeO2 removal and correlated with the transition of G2/M–G1 phase of the cells. This result suggests that GeO2 treatment reduces Cdk1 activity and causing the G2 arrest in CHO cells. [Copyright &y& Elsevier]