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ANALYSIS OF IN VITRO AND IN VIVO DNA STRAND BREAKS INDUCED BY TRIHALOMETHANES (THMS)
Citation:
Geter, D. R., L W. Chang, C. A. Granville, M H. George, AND A B. DeAngelo. ANALYSIS OF IN VITRO AND IN VIVO DNA STRAND BREAKS INDUCED BY TRIHALOMETHANES (THMS). Presented at Annual Meeting of Environmental Mutagen Society, Anchorage, Alaske, 4/27/02-5/2/02.
Description:
Analysis of In Vitro and In Vivo DNA Strand Breaks Induced by Trihalomethanes (TRMs)
The THMs are the most widely distributed and the most concentrated of the cWorine disinfection by-products (D BPs) found in finished drinking water. All of the THMs, cWoroform (CHCI3), bromodicWoromethane (CHBrCI2), dibromocWoromethane (CHBr2Cl), and bromoform
(CHBr3) are found in ratios that reflect the bromide concentration of the source water. Since
large populations obtain their water from municipalities using cWorine as the primary source of disinfection, it is certain that they are chronically exposed to low levels of THMs which have been implicated as an increased risk of colorectal and bladder cancer. Toxicological studies
demonstrated that TRMs administered by corn oil gavage induced large bowel denocarcinoma in rats (CRBrC12 and CHBr3), renal tubular cell adenocarcinoma in male mice (CHBrC12) 8;ild rats (CRC13 and CHBrCI2), and hepatocellular carcinoma in male and/or female mice (CRC13 and CRBrC12). In this study we investigated the ability of the TRMs to induce DNA strand breaks (SB) using the DNA alkaline unwinding assay [I] in CCRF-CEM cells and rat epatocytes exposed in vitro and [2] after administration to rats by aqueous gavage or in drinking water. Exposing CCRF-CEM cells to 1,5 and 10 mM TRMs for 2 h produced DNA SB. The order of activity was CRBr3>CRBr2Cl>CRBrC12; CRC13 was inactive. After a 22 h recovery period, cells exposed to 5 and 10 mM CRBr3 or 10 mM CHBr2Cl did not recover. Treating rat atocytes in primary culture with 1 -10 mM CRBr3 and CRBr2Cl for 4 h produced dose dependant DNA SB and cellular toxicity. CRBrCl2 and CRC13 produced no toxicity or DNA SB. The brominated THMs administered by aqueous gavage (0.3 and 0.6 mmol/kg; 4 hrs) and in the drinking water (0.6, 1.2 and 2.4 g/I-,; 2 and 5 weeks) to male F344 rats produced no increase in DNA SB of liver, kidney, or duodenum. These data demonstrate that the brominated TRMs administered in an aqueous vehicle possess a specific type of genotoxicity (DNA SB) in cells with low etabolic capability (CCRF-CEM, duodenal epithelial cells), but not in cells with an active P450 enzyme system (hepatocyte, kidney tubule).
(This is an abstract of a proposed presentation and does not necessarily reflect the opinion of the EPA).