Skip Navigation



Carcinogenesis Advance Access published online on March 24, 2005
Carcinogenesis, doi:10.1093/carcin/bgi073
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
26/7/1307    most recent
bgi073v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Nair, J.
Right arrow Articles by Bartsch, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nair, J.
Right arrow Articles by Bartsch, H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oupjournals.org
Received December 21, 2004
Revised March 11, 2005
Accepted March 12, 2005

CARCINOGENESIS

Apoptosis and age-dependant induction of nuclear and mitochondrial etheno-DNA adducts in Long-Evans Cinnamon (LEC) rats: enhanced DNA damage by dietary curcumin upon copper accumulation

Jagadeesan Nair 1*, Susanne Strand 2, Norbert Frank 1, Jutta Knauft 1, Horst Wesch 3, Peter R. Galle 2, and Helmut Bartsch 1

1 Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany
2 First Department of Internal Medicine, Johannes Gutenberg-University Mainz, Germany
3 Division of Oncological Diagnostics and Therapy, German Cancer Research Center (DKFZ), Heidelberg

* To whom correspondence should be addressed.
Jagadeesan Nair, E-mail: j.nair{at}dkfz.de


  Abstract

Long-Evans Cinnamon (LEC) rats, a model for human Wilson's disease, develop chronic hepatitis and liver tumors due to copper accumulation and induced oxidative stress. Lipid peroxidation (LPO)-induced etheno-DNA adducts in nuclear- and mitochondrial DNA together with apoptosis was measured in LEC rat liver. Levels of etheno-DNA adducts (1,N6-ethenodeoxyadenosine and 3,N4-ethenodeoxycytidine) increased with age reaching a peak at 8 and 12 weeks in nuclear and mitochondrial DNA, respectively. This is the first demonstration that etheno-DNA adducts are also formed in mitochondrial DNA. Apoptosis was assessed by TUNEL+ cells in liver sections. CD95L RNA expression was also measured by in situ hybridization in the same sections. The highest nuclear DNA adduct levels coincided with a reduced apoptotic rate at 8 weeks. Mitochondrial DNA adducts peaked at 12 weeks that coincided with the highest apoptotic rate, suggesting a link of etheno-DNA adducts in mitochondrial DNA to apoptosis. The DNA damage in liver was further enhanced and sustained by 0.5 % curcumin in the diet. Treatment for 2 weeks elevated etheno-DNA adducts 9-25 fold in nuclear DNA and 3-4 fold in mitochondrial DNA, providing a plausible explanation why in our earlier study (Frank et al., Mutation Research, 2003), curcumin failed to prevent liver tumors in LEC rats. Our results also confirm the reported in vitro DNA damaging potential of curcumin in the presence of copper ions by reactive oxygen species. LPO-induced adduct formation in nuclear and mitochondrial DNA appear as early lesions in LEC rat liver carcinogenesis and are discussed in relation to apoptotic events in malignant disease progression.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 CarcinogenesisHome page
H. Bartsch
Dr Jagadeesan Nair, Senior Scientist at the German Cancer Research Center (DKFZ) 1953-2007
Carcinogenesis, May 1, 2008; 29(5): 887 - 888.
[Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.