A G2/M growth arrest response to low-dose intermittent H2O2 in normal uroepithelial cells.
- M Chien
- C Rinker-Schaeffer
- W M Stadler
Affiliations: Sections of Urology and Hematology/Oncology, Departments of Surgery and Medicine, Prostate Cancer Program, Cancer Research Center, University of Chicago, IL 60637, USA.
- Published online on: September 1, 2000 https://doi.org/10.3892/ijo.17.3.425
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Studies in fibroblasts have shown that H2O2, as a model for oxidative damage, leads to a G1 growth arrest phenotypically similar to senescence. These observations as well as the observation that bladder cancer is associated with deletions of CDKN2, a gene important in normal senescence, led us to examine normal urothelial cell response to H2O2. We hypothesized that low dose H2O2 exposure would lead to p16 and/or p14arf mediated senescence. We show that H2O2 leads to endogenous beta-galactosidase expression similar to senescence, but instead of G1 arrest, it leads to G2/M growth arrest without induction of either p16 or p14arf. Lack of p21 induction and a similar G2/M growth arrest in E6 immortalized uroepithelial cells suggests that this response is independent of p53 as well. An increased level of cdc2 tyrosine-15 phosphorylation following H2O2 treatment suggests that the observed growth arrest is mediated by a G2 checkpoint mechanism.