© 1992 Oxford University Press
research-article |
2,4,5-Trichlorophenoxyacetic Acid Influence on 2,6-Dinitrotoluene-Induced Urine Genotoxicity in Fischer 344 Rats: Effect on Gastrointestinal Microflora and Enzyme Activity
*Health Effects Research Laboratory, U.S. Environmental Protection Agency Research Thangle Park, North Carolina 27711
Division of Laboratory Medicine, University of North Carolina Chapel Hill, North Carolina 27599
Environmental Health Research and Testing, Inc P.O. Box 12199, Research Triangle Park, North Carolina 27709
Received April 18, 1991; accepted August 12, 1991
2,4,5-Trichlorophenoxyacetic acid (2,4,5-T) and 2,6-dinitrotoluene (2,6-DNT) are hazardous chemicals that have potential harmful effects. 2,6-DNT is recognized as a hepatotoxicant while 2,4,5-T, a component of Agent Orange, is also suspect. 2,6-DNT requires both oxidative and reductive metabolism to elicit genotoxic effects. To determine what effect 2,4,5-T had on 2,6-DNT metabolism, intestinal enzymes, microbial populations, and urine mutagenicity were examined during 2,4,5-T treatment. Weanling Fischer 344 male rats were treated daily with 54.4 mg/kg 2,4,5-T by gavage for 4 weeks. One, two, and four weeks after the initial 2,4,5-T dose, rats were administered (po) 2,6-DNT (75 mg/kg) and urine was collected for 24 hr in metabolism cages. Azo reductase, nitroreductase, ß-glucuronidase, dechlorinase, and dehydrochlorinase activities were examined concurrently. Treatment of rats for 1 week reduced the transformation of 2,6-DNT to mutagenic urinary metabolites. This was accompanied by a decrease in the fecal anaerobic microorganisms. The elimination ofLactobacillus fermentum from the small intestine and cecum of treated animals accompanied a significant increase in oxygen-tolerant lactobacilli and other unidentified aerobic microorganisms. However, there were no significant alterations in the intestinal enzyme activities examined. By 2 weeks of 2,4,5-T treatment, microbiota and urine genotoxicity returned to the levels observed in control animals. This trend continued for the duration of the experiment After 2 weeks, while cecal nitroreductase and azo reductase activities increased, small intestinal ß-glucuronidase activity decreased. By 4 weeks, treated and untreated animal intestinal enzyme activities were indistinguishable. The transient increase in azo reductase and nitroreductase after treatment with 2,4,5-T for 2 weeks may have been counteracted by the reduced ß-glucuronidase activity, thus resulting in no change in 2,6-DNT-derived urine mutagenicity. However, other environmental chemicals, unaffected by ß-glucuronidase, potentially could be activated by 2,4,5-T exposure.