ToxSci Advance Access originally published online on September 1, 2004
Toxicological Sciences 2004 82(1):62-69; doi:10.1093/toxsci/kfh266
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Toxicological Sciences vol. 82 no. 1 © Society of Toxicology 2004; all rights reserved.
Effect of Dibromoacetic Acid on DNA Methylation, Glycogen Accumulation, and Peroxisome Proliferation in Mouse and Rat Liver
Department of Pathology, Medical College of Ohio, Toledo, Ohio 43614-5806
Received May 18, 2004; accepted August 4, 2004
Dibromoacetic acid (DBA) is a drinking water disinfection by-product. Its analogs, dichloroacetic acid (DCA) and trichloroacetic acid (TCA), are liver carcinogens in rodents. We evaluated the ability of DBA to cause DNA hypomethylation, glycogen accumulation, and peroxisome proliferation that are activities previously reported for the two other haloacetic acids. Female B6C3F1 mice and male Fischer 344 rats were administered 0, 1,000, and 2,000 mg/l DBA in drinking water. The animals were euthanized after 2, 4, 7, and 28 days of exposure. Dibromoacetic acid caused a dose-dependent and time-dependent decrease of 20%–46% in the 5-methylcytosine content of DNA. Hypomethylation of the c-myc gene was observed in mice after 7 days of DBA exposure. Methylation of 24 CpG sites in the insulin-like growth factor 2 (IGF-II) gene was reduced from 80.2% ± 9.2% to 18.8% ± 12.9% by 2,000 mg/l DBA for 28 days. mRNA expression of the c-myc and IGF-II genes in mouse liver was increased by DBA. A dose-dependent increase in the mRNA expression of the c-myc gene was also observed in rats. In both mice and rats, DBA caused dose-dependent accumulation of glycogen and an increase of peroxisomal lauroyl-CoA oxidase activity. Hence, DBA, like DCA and TCA, induced hypomethylation of DNA and of the c-myc and IGF-II genes, increased mRNA expression of both genes, and caused peroxisome proliferation. Again like DCA, DBA also induced glycogen accumulation. These results indicate that DBA shares biochemical and molecular activities in common with DCA and/or TCA, suggesting that it might also be a liver carcinogen.
Key Words: dibromoacetic acid; DNA hypomethylation; insulin-like growth factor 2; liver; c-myc; peroxisome proliferation.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Z. K. Wen, W. Xu, L. Xu, Q. H. Cao, Y. Wang, Y. W. Chu, and S. D. Xiong DNA hypomethylation is crucial for apoptotic DNA to induce systemic lupus erythematosus-like autoimmune disease in SLE-non-susceptible mice Rheumatology, December 1, 2007; 46(12): 1796 - 1803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. P. Tryndyak, L. Muskhelishvili, O. Kovalchuk, R. Rodriguez-Juarez, B. Montgomery, M. I. Churchwell, S. A. Ross, F. A. Beland, and I. P. Pogribny Effect of long-term tamoxifen exposure on genotoxic and epigenetic changes in rat liver: implications for tamoxifen-induced hepatocarcinogenesis Carcinogenesis, August 1, 2006; 27(8): 1713 - 1720. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Tao, W. Wang, L. Li, P. K. Kramer, and M. A. Pereira DNA Hypomethylation Induced by Drinking Water Disinfection By-Products in Mouse and Rat Kidney Toxicol. Sci., October 1, 2005; 87(2): 344 - 352. [Abstract] [Full Text] [PDF]
|
|