Genotoxicity As A Biomarker For Inflammation

Tech ID: 20440 / UC Case 2009-341-0

Summary

Researchers at the UCLA Departments of Pathology and Laboratory Medicine have identified a means to use systemic genotoxicity as a sensitive biomarker for mucosal inflammation, pulmonary inflammation, and their progression to inflammatory bowel disease-associated dysplasia and asthma.

Background

Chronic inflammation plays an essential role in tumorigenesis, but the underlying molecular mechanisms linking inflammation and cancer remain to be explored. Inflammatory mediators present in tumor environment, including cytokines and growth factors, reactive oxygen species, and reactive nitrogen species have been implicated in the etiology of inflammation-associated cancers. In particular, reactive oxygen species (ROS) serve as mediators participating in host defense, or as chemo-attractants recruiting leukocytes to wounds, influencing the inflammatory reaction in damaged tissues. ROS can also induce changes in chromosomal DNA resulting in genomic instability, and serve as signaling molecules affecting tumor cell proliferation, survival, metabolism, angiogenesis and metastasis.

Innovation

Researchers at UCLA have revealed systemic genotoxicity as a feature of subclinical and severe chronic intestinal inflammation, as well as in allergenic asthma. They have shown that both intestinal and pulmonary inflammation manifest a global effect, inducing systemic genotoxicity in the peripheral blood, as indicated by DNA single- and double-strand breaks, oxidative base damage to peripheral leukocytes, as well as micronuclei formation in erythroblasts. Their findings support the involvement of systemic genotoxicity in chronic inflammation and its role in contributing to inflammation-associated carcinogenesis. Systemic genotoxicity may therefore serve as a sensitive biomarker of inflammation and its progression to cancer.

Applications

Collect a small quantity of blood and quantify the level of genotoxicity by immunostaining and other methods. The level of genotoxicity directly correlates with the level of inflammation. This approach can be used to:

  • Monitor chronic inflammation and its progression to cancer
  • Monitor treatment efficacy and disease management in patients over time

 

Advantages

  • Requires only a small amount of blood for genotoxicity testing, instead of invasive procedures 
  • Less labor intensive and more time efficient for patient sample analysis
  • Allows detection of sub-clinical inflammation

State Of Development

Systemic genotoxicity has been validated in dextran sulfate sodium (DSS)-induced colitis mouse models, as well genetic knockout mouse with immune-mediated colitis.

Related Materials

Patent Status

Country Type Number Dated Case
United States Of America Issued Patent 8,951,740 02/10/2015 2009-341
United States Of America Issued Patent 8,940,491 01/27/2015 2009-341
 

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Inventors

  • Schiestl, Robert H.

Other Information

Keywords

Genotoxicity, systemic genotoxicity, biomarker, inflammation, chronic inflammation, mucosal inflammation, intestinal inflammation, pulmonary inflammation, inflammatory bowel disease, diagnostic

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