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Toxicological Sciences 56, 282-289 (2000)
Copyright © 2000 by the Society of Toxicology

The Disinfection By-Products Dichloro-, Dibromo-, and Bromochloroacetic Acid Impact Intestinal Microflora and Metabolism in Fischer 344 Rats upon Exposure in Drinking Water

S. E. George*,1, G. M. Nelson*, A. E. Swank*, L. R. Brooks*, K. Bailey{dagger}, M. George* and A. DeAngelo*

* Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina; and {dagger} Department of Biology, North Carolina Central University, Durham, North Carolina

Human consumption of chlorinated drinking water has been linked epidemiologically to bladder, kidney, and rectal cancers. The disinfection by-product (DBP) dichloroacetic acid is a hepatocarcinogen in Fischer 344 rats and B6C3F1 mice. The objective of this study is to determine the effect of the DBPs dichloro-, bromochloro-, and dibromoacetic acids (DCA, BCA, DBA) on intestinal microbial populations and their metabolism, with emphasis on enzymes involved in the bioactivation of procarcinogens and promutagens. One-month-old male Fischer 344 rats were provided water ad libitum containing 1 g/l DCA, BCA, or DBA for up to 5 weeks. At 1, 3, and 5 weeks of treatment, ß-glucuronidase (GLR), ß-galactosidase (GAL), ß-glucosidase (GLU), nitroreductase (NR), azoreductase (AR), and dechlorinase (DC) activities were determined in cecal and small and large intestinal homogenates. After 5 weeks of treatment, intestinal populations were enumerated on selective media. Cecal GAL (DCA, BCA, DBA) and GLR (DCA, DBA) activities were reduced after 1 and 3 weeks of treatment and GAL activity was elevated at 5 weeks (BCA). Large intestinal GAL (DCA, BCA) and GLU (DCA, BCA, DBA) activities were elevated after 5 weeks of treatment. Week 5 cecal AR (DCA, BCA, DBA), NR (DCA), and DC (DCA, DBA) activities were reduced. Even though some significant changes in intestinal populations were observed, use of selective media was not sensitive enough to explain fluctuations in enzyme activity. Haloacetic acids in the drinking water alter intestinal metabolism, which could influence bioactivation of promutagens and procarcinogens in the drinking water.

Key Words: disinfection by-products; intestinal microflora; bioactivation; nitroreductase; azoreductase; dechlorinase; intestinal metabolism; dichloroacetic acid; dibromoacetic acid; bromochloroacetic acid; bromochloroacetic acid.


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G. M. Nelson, A. E. Swank, L. R. Brooks, K. C. Bailey, and S. E. George
Metabolism, Microflora Effects, and Genotoxicity in Haloacetic Acid-Treated Cultures of Rat Cecal Microbiota
Toxicol. Sci., April 1, 2001; 60(2): 232 - 241.
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