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.