Abstract
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. © 2002 Elsevier Science Ireland Ltd. All rights reserved.