Abstract |
The organochlorine pesticide, pentachlorophenol, a potent sulfotransferase inhibitor, reportedly reduces the binding of 2,6-dinitrotoluene, an industrial hepatocarcinogen to hepatic DNA by 95% after a single i.p. injection. Activation of 2,6-dinitrotoluene to genotoxic metabolites involves enzymes in both the liver and the intestinal flora. Since pentachlorophenol also has bactericidal activity and induces hepatic mixed function oxidase activity after longer treatment, the effect of pentachlorophenol on intestinal enzyme activity and the biotransformation of 2,6-dinitrotoluene to genotoxic metabolites was studied after 1, 2, 4, and 5 weeks of treatment. Male Fischer 344 rats were dosed daily, by gavage, with either 20 mg/kg pentachlorophenol or the peanut oil vehicle. After 1, 2, 4, and 5 weeks, select control and treated animals were injected p.o. with 75 mg/kg 2,6-dinitrotoluene and transferred to metabolism cages, where urine was collected for 24 hr and tested for mutagenic activity by the Ames Salmonella typhimurium reversion assay. |