Skip Navigation


ToxSci Advance Access originally published online on July 13, 2005
Toxicological Sciences 2005 87(2):344-352; doi:10.1093/toxsci/kfi257
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
87/2/344    most recent
kfi257v1
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 arrow Search for citing articles in:
ISI Web of Science (3)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Tao, L.
Right arrow Articles by Pereira, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tao, L.
Right arrow Articles by Pereira, M. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

DNA Hypomethylation Induced by Drinking Water Disinfection By-Products in Mouse and Rat Kidney

Lianhui Tao*,1, Wei Wang*, Long Li{dagger}, Paula K. Kramer{dagger} and Michael A. Pereira*

* Department of Internal Medicine, Division of Hematology and Oncology, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210, and {dagger} Department of Pathology, Medical College of Ohio, 3055 Arlington Avenue, Toledo, Ohio 43614

Received March 11, 2005; accepted July 7, 2005

Bromodichloromethane (BDCM), chloroform, dibromoacetic acid (DBA), dichloroacetic acid (DCA), and trichloroacetic acid (TCA) are chlorine disinfection by-products (DBPs) found in drinking water that have indicated renal carcinogenic and/or tumor promoting activity. We have reported that the DBPs caused DNA hypomethylation in mouse liver, which correlated with their carcinogenic and tumor promoting activity. In this study, we determined their ability to cause renal DNA hypomethylation. B6C3F1 mice were administered DCA or TCA concurrently with/without chloroform in their drinking water for 7 days. In male, but not female mouse kidney, DCA, TCA, and to a lesser extent, chloroform decreased the methylation of DNA and the c-myc gene. Coadministering chloroform increased DCA but not TCA-induced DNA hypomethylation. DBA and BDCM caused renal DNA hypomethylation in both male B6C3F1 mice and Fischer 344 rats. We have reported that, in mouse liver, methionine prevented DCA- and TCA-induced hypomethylation of the c-myc gene. To determine whether it would also prevent hypomethylation in the kidneys, male mice were administered methionine in their diet concurrently with DCA or TCA in their drinking water. Methionine prevented both DCA- and TCA-induced hypomethylation of the c-myc gene. The ability of the DBPs to cause hypomethylation of DNA and of the c-myc gene correlated with their carcinogenic and tumor promoting activity in mouse and rat kidney, which should be taken into consideration as part of their risk assessment. That methionine prevents DCA- and TCA-induced hypomethylation of the c-myc gene would suggest it could prevent their carcinogenic activity in the kidney.

Key Words: dichloroacetic acid; trichloroacetic acid; DNA hypomethylation; kidney.


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
 International Journal of ToxicologyHome page
D. Desaulniers, G.-h. Xiao, H. Lian, Y.-L. Feng, J. Zhu, J. Nakai, and W. J. Bowers
Effects of Mixtures of Polychlorinated Biphenyls, Methylmercury, and Organochlorine Pesticides on Hepatic DNA Methylation in Prepubertal Female Sprague-Dawley Rats
International Journal of Toxicology, July 1, 2009; 28(4): 294 - 307.
[Abstract] [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.