Bile acids have been demonstrated, through the use of animal models and clinical association studies, to play a role in neoplastic development in Barrett's metaplasia. How specific bile acids promote neoplasia is as yet unknown, as are the exact identities of the important bile acid subtypes. The combination of bile subtype with appropriate pH is critical, as pH alters bile acid activity enormously. Hence glycine-conjugated bile acids are involved in neoplastic development at acidic pH (pH ~4), and unconjugated bile acids are involved in neoplastic development at more neutral pH (~6). Bile acids (at the appropriate pH) are potent DNA-damaging agents, due to the induction of ROS (reactive oxygen species), which are mainly induced by bile-induced damage to mitochondrial membranes, allowing leakage of ROS into the cytosol. These ROS also induce pro-survival signalling pathways [e.g. via PKC (protein kinase C)-dependent NF-κB (nuclear factor κB) activity]. Interestingly, NOS (nitric oxide synthase), through induction of NO may exacerbate this NF-κB activity and form a positive-feedback loop to amplify the activation of NF-κB by deoxycholic acid in particular. This combination of induced DNA damage and cell survival by bile acids is of major importance in neoplasia. Antioxidants and the tertiary bile acid UDCA (ursodeoxycholic acid) can block bile-induced DNA damage and bile-induced NF-κB activity, and should be considered in chemopreventative strategies.
Skip Nav Destination
Article navigation
April 2010
- Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Conference Article|
March 22 2010
The role of secondary bile acids in neoplastic development in the oesophagus
James Cronin;
James Cronin
*Institute of Life Science, Swansea School of Medicine, Swansea University, Swansea SA2 8PP, U.K.
Search for other works by this author on:
Lisa Williams;
Lisa Williams
†Royal Glamorgan Hospital, Ynysmaerdy, Llantrisant CF72 8XR, U.K.
Search for other works by this author on:
Elizabeth McAdam;
Elizabeth McAdam
*Institute of Life Science, Swansea School of Medicine, Swansea University, Swansea SA2 8PP, U.K.
Search for other works by this author on:
Zak Eltahir;
Zak Eltahir
*Institute of Life Science, Swansea School of Medicine, Swansea University, Swansea SA2 8PP, U.K.
Search for other works by this author on:
Paul Griffiths;
Paul Griffiths
‡Morriston Hospital, ABM Trust, Morriston, Swansea SA6 6NL, U.K.
Search for other works by this author on:
John Baxter;
John Baxter
‡Morriston Hospital, ABM Trust, Morriston, Swansea SA6 6NL, U.K.
Search for other works by this author on:
Gareth Jenkins
Gareth Jenkins
1
*Institute of Life Science, Swansea School of Medicine, Swansea University, Swansea SA2 8PP, U.K.
1To whom correspondence should be addressed (email g.j.jenkins@swansea.ac.uk).
Search for other works by this author on:
Biochem Soc Trans (2010) 38 (2): 337–342.
Article history
Received:
July 23 2009
Citation
James Cronin, Lisa Williams, Elizabeth McAdam, Zak Eltahir, Paul Griffiths, John Baxter, Gareth Jenkins; The role of secondary bile acids in neoplastic development in the oesophagus. Biochem Soc Trans 1 April 2010; 38 (2): 337–342. doi: https://doi.org/10.1042/BST0380337
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.