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Atrazine treatment potentiates excretion of mutagenic urine in 2, 6‐dinitrotoluene‐treated fischer 344 rats
Author(s) -
George S. E.,
Chadwick R. W.,
Kohan M. J.,
Allison J. C.,
Warren S. H.,
Williams R. W.
Publication year - 1995
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.2850260212
Subject(s) - chemistry , nitroreductase , urine , excretion , atrazine , urinary system , mutagen , ames test , metabolism , medicine , endocrinology , pharmacology , carcinogen , enzyme , salmonella , biochemistry , pesticide , bacteria , biology , genetics , agronomy
Atrazine (ATZ), an s‐triazine herbicide, is a widespread environmental contaminant. The hepatocar‐cinogenic component of technical grade dinitrotoluene, 2, 6‐dinitrotoluene (2, 6‐DNT, 19.5%), is a byproduct of trinitrotoluene synthesis and is found at production sites. This study explores the effect of ATZ treatment on the bioactivation of the promutagen, 2, 6‐DNT. Male Fischer 344 rats (5 weeks old) were administered 50 mg/kg of ATZ by gavage for 5 weeks. At 1, 3, and 5 weeks, both DMSO‐control and ATZ‐pretreated rats were treated p.o. with 75 mg/kg of 2, 6‐DNT and were housed in metabolism cages for urine collection. Sulfatase‐and β‐glucuronidase‐treated, concentrated urine was bioassayed for urinary mutagens in a microsuspension modification of the Salmonella assay with and without metabolic activation. No significant change in mutagen excretion was observed in ATZ‐treated rats; however, an elevation in direct‐acting urine mutagens from rats receiving ATZ and 2, 6‐DNT at weeks 1 (359 ± 68 vs. 621 ± 96 revertants/ml) and 5 (278 ± 46 vs. 667 ± 109 revertants/ml) of treatment was observed. The increase in production of urinary mutagens was accompanied by an elevation in small intestinal nitroreductase activity. Increases in large intestinal nitroreductase and β‐glucuronidase were observed after 5 weeks. There was no apparent effect of ATZ following 5 weeks of treatment on the production of 2, 6‐DNT‐derived hepatic DNA adducts. ATZ treatment modifies intestinal enzymes responsible for promutagen bioactivation, and potentiates the excretion of mutagenic urine in 2, 6‐DNT‐treated animals. © 1995 Wiley‐liss, Inc. This article i s a US Government work and, as such, i s in the public domain in the United States of America.