2,4,5-Trichlorophenoxyacetic acid influence on 2,6-dinitrotoluene-induced urine genotoxicity in Fischer 344 rats: Effect on gastrointestinal microflora and enzyme activity

Journal of Applied Bacteriology

Allison

et al. 1994

The succession of gut bacteria and selected intestinal enzyme activities in developing 7-35-d-old rats was studied. Aerobes and anaerobes were identified as members of four broad major bacterial groups, i.e. Gram-positive rods, Gram-positive cocci, Gram-negative rods and obligate anaerobes. The enzyme activities of nitro and azo reductases, beta-glucuronidase, dechlorinase and dehydrochlorinase were determined by anaerobic incubation of intestinal homogenates with 3,4-dichloronitrobenzene, methyl orange, p-nitrophenyl-beta-D-glucuronide, and p,p'-DDT respectively. Nitroreductase and azo reductase activities increased significantly with the appearance of anaerobes in the large intestine. No increase in either nitroreductase or azo reductase activities in the small intestine was found. The early and high level of beta-glucuronidase activity in the small and large intestines coincided with high numbers of coliforms recovered in 7 and 14 d animals. Dehydrochlorinase activity appeared early but was undetectable at both 21 and 28 d. Its activity increased at 35 d. Dechlorinase activity was variable in development. The rapid changes in the microbial flora and intestinal enzyme activities may influence the susceptibility of pre-pubescent rats to a variety of toxicants. Therefore, age-dependent toxicity may be important in the risk assessment of some environmental chemicals.

Section: Introductionmentioning

confidence: 99%

Microbial succession and intestinal enzyme activities in the developing rat

Chang

Journal of Applied Bacteriology

Allison

et al. 1994

“…Previous work in this laboratory indicated that pretreatment of rats with pentachlorophenol (PCP) George et al, 1991) or with Aroclor 1254 (Chadwick et al, 1993) potentiated the genotoxicity of the industrial chemical DNT. On the other hand, pretreatment with the organochlorine herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) produced only a transient antagonism of DNT toxicity (George et al, 1992). DNT, the primary isomer responsible for the hepatocarcinogenicity of technical-grade dinitrotoluene (Leonard et al, 1987), is used in the manufacture of polyurethane foams, coatings, and elastomers.…”

Section: R W Chadwick Et Almentioning

confidence: 99%

Potentiation of 2,6‐dinitrotoluene genotoxicity in fischer 344 rats by pretreatment with coal tar creosote

Journal of Toxicology and Environmental Health

George

Kohan

et al. 1995

Pretreatment of male Fischer 344 rats for 5 wk with coal tar creosote, a coal distillation product that is widely used as a wood preservative, potentiated the excretion of urinary mutagens in 2,6-dinitrotoluene (DNT) treated rats. Creosote increased the bioactivation of DNT to significantly greater levels of urinary genotoxic metabolites and/or formed DNA adducts in the liver. A significant increase in the excretion of mutagenic DNT metabolites was observed after the first week of creosote treatment, peaked at wk 3, and then decreased by 33% after 5 wk of treatment. Nevertheless, there was a significant increase (66%) in the formation of DNT-derived DNA adducts in the livers of rats treated with DNT plus creosote at wk 5. Increased cecal beta-glucuronidase activity and reduced small intestinal nitroreductase activity may play roles in the bioactivation of DNT. The excretion of mutagenic DNT metabolites supplies useful information about the bioactivation of DNT; it does not provide a useful index of DNT-derived hepatic DNA adduct formation. Such interactions could be important to predictive risk assessment because the overall cancer risk of such chemical mixtures may exceed the sum of the component risks.

Atrazine treatment potentiates excretion of mutagenic urine in 2, 6‐dinitrotoluene‐treated fischer 344 rats

George

Environ and Mol Mutagen

Kohan

et al. 1995

Atrazine (ATZ), an s-triazine herbicide, is a widespread environmental contaminant. The hepatocarcinogenic 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 beta-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 beta-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.