Vanadate Induces G2/M Phase Arrest in p53-Deficient Mouse Embryo Fibroblasts

Details

• Personal Author:
  Chen F ; Huang C ; Shi X ; Zhang Z
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Carcinogens Hazardous Substances Neoplasms Occupational Health Safety Stress, Psychological Vanadium Compounds
• Keywords:
  Author Keywords: Vanadium Biological-systems Carcinogenesis Cell-growth Cell Cycle Environmental-stress G0 Phase G1 Phase G2 Phase Oncogene Protein P21 Protein Kinases Protein P53 Proteins Reactive Oxygen Species S Phase Toxic-effects Tumors Vanadium-compounds

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• ISSN:
  0731-8898
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2 ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  223-231
• Volume:
  21
• Issue:
  3
• NIOSHTIC Number:
  nn:20022918
• Citation:
  J Environ Pathol Toxicol Oncol 2002 Jul; 21(3):223-231
• Contact Point Address:
  Xianglin Shi, Ph D, Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  xshi@cdc.gov
• CAS Registry Number:
  Vanadium (CAS RN 7440-62-2)
• Federal Fiscal Year:
  2002
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Environmental Pathology, Toxicology, and Oncology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:bfdd8ef723da2a2b1afb245a5407626ec8610f879f6bcc018470197b2dd5ebce9d8e4fd19e73e6dd82582cfa02bf5de3291f923d8f34804cff698219d546ef46
• Download URL:
  https://stacks.cdc.gov/view/cdc/199532/cdc_199532_DS1.pdf
• File Type:
  [PDF - 428.98 KB ]