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Inflammation and Cancer

Volume 512 of the series Methods in Molecular Biology™ pp 15-28

Molecular Analysis of Genetic Instability Caused by Chronic Inflammation

  • Bin YanAffiliated withDepartment of Radiation Oncology, Virginia Commonwealth University Health System
  • , Yuanlin PengAffiliated withDepartment of Environmental & Radiological Health Sciences, Colorado State University
  • , Chuan-Yuan LiAffiliated withDepartment of Radiation Oncology, University of Colorado Health Sciences Center

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Summary

Genetic instability is a hallmark of human cancers. It is the driving force for tumor development as it facilitates the accumulation of mutations in genes that regulate cell death and proliferation and therefore promotes malignant transformation. Chronic inflammation is a common underlying condition for human tumor development, accounting for approximately 20% of human cancers. TNFα is an important inflammation cytokine and is crucial to the development of inflammation-associated cancers. We have shown that TNFα can cause DNA damages through reactive oxygen species (ROS). TNFα treatment in cultured cells resulted in increased gene mutations, gene amplification, micronuclei formation and chromosomal instability. Antioxidants significantly reduced TNFα-induced genetic damage. In addition, TNFα treatment alone led to increased malignant transformation of mouse embryo fibroblasts, which could be partially suppressed by antioxidants. Therefore, genetic instability plays an important role in inflammation-associated cancers.

Key words

Genetic instability Inflammation Cancer Reactive oxygen species 8-Oxo-deoxyguanosine