Vanadate Induces G2/M Phase Arrest in p53 - Deficient Mouse Embryo Fibroblasts.
Zhang-Z; Chen-F; Huang-C; Shi-X
J Environ Pathol Toxicol Oncol 2002 21(3):223-231
Vanadium compounds exert potent toxic and carcinogenic effects on a wide variety of biological systems. The mechanisms involved in their toxicity and carcinogenesis require investigation. Cell growth arrest and its regulation are important mechanisms in maintaining genomic stability and integrity in response to environmental stress. The p53 tumor suppressor plays a central role in the regulation of the normal cell cycle. To investigate the role of p53 in vanadate-induced cell growth arrest and its regulation, two cell lines--normal mouse embryo fibroblasts [p53(+/+)] and p53-deficient mouse embryo fibroblasts [p53(-/-)],- were used in this study. Flow cytometry was used to analyze cell growth arrest at G0/G1, S, or G2/M phase. Western blotting analysis was performed to determine several cell growth regulatory proteins. The results showed that in p53(-/-) cells vanadate induced G2/M phase arrest in a dose- and time-dependent manner without alteration of S phase. In p53(+/+) cells, vanadate treatment increased the S phase with no significant change in the G2/M phase. Furthermore, Western blotting results showed that in p53(-/-) cells vanadate caused cdc25C degradation and activation of phospho-cdc2 without alteration of the p21 level. In p53(+/+) cells, vanadate increased the expression of p21 and degraded cdc25A instead of cdc25C without any effect on cdc2. These results demonstrate that vanadate induced G2/M phase arrest in p53-deficient mouse embryo fibroblasts, and promoted S phase entry in p53 wild-type mouse embryo fibroblasts.
Vanadium-compounds; Toxic-effects; Carcinogens; Biological-systems; Carcinogenesis; Cell-growth; Environmental-stress; Tumors; Proteins
Xianglin Shi, Ph D, Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
Research Tools and Approaches; Cancer Research Methods
Journal of Environmental Pathology, Toxicology, and Oncology