HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

DNA hypomethylation induced by drinking water disinfection by-products in mouse and rat kidney.

Abstract
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.
AuthorsLianhui Tao, Wei Wang, Long Li, Paula K Kramer, Michael A Pereira
JournalToxicological sciences : an official journal of the Society of Toxicology (Toxicol Sci) Vol. 87 Issue 2 Pg. 344-52 (Oct 2005) ISSN: 1096-6080 [Print] United States
PMID16014735 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Acetates
  • Disinfectants
  • Trichloroacetic Acid
  • dibromoacetic acid
  • Dichloroacetic Acid
  • Methionine
Topics
  • Acetates (chemistry)
  • Animals
  • DNA Methylation (drug effects)
  • Dichloroacetic Acid (chemistry)
  • Disinfectants (toxicity)
  • Female
  • Genes, myc (genetics)
  • Kidney (drug effects, metabolism)
  • Male
  • Methionine (pharmacology)
  • Mice
  • Rats
  • Risk Assessment
  • Trichloroacetic Acid (chemistry)
  • Water Supply (analysis)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: