Record Display for the EPA National Library Catalog


OLS Field Name OLS Field Data
Main Title Potentiation of 2,6-Dinitrotoluene Genotoxicity in Fischer 344 Rats by Pretreatment with Pentachlorophenol.
Author Chadwick, R. W. ; George, S. E. ; Chang, J. ; Kohan, M. J. ; Dekker, J. P. ;
CORP Author North Carolina Univ. at Chapel Hill. ;Environmental Health Research and Testing, Inc., Research Triangle Park, NC.;Health Effects Research Lab., Research Triangle Park, NC.
Publisher c1991
Year Published 1991
Report Number EPA-R-815941; EPA/600/J-91/047;
Stock Number PB91-191544
Additional Subjects Mutagens ; Pesticides ; Sulfotransferases ; Enzyme inhibitors ; Mutagenicity tests ; Rats ; Metabolic activation ; DNA damage ; Chemical stimulation ; Reprints ; Dinitrotoluenes ; Pentachlorophenol ; Liver enzymes
Library Call Number Additional Info Location Last
NTIS  PB91-191544 Most EPA libraries have a fiche copy filed under the call number shown. Check with individual libraries about paper copy. 09/04/1991
Collation 14p
The organochlorine pesticide, pentachlorophenol (PCP), a potent sulfotransferase inhibitor, reduces binding of the hepatocarcinogen, 2,6-dinitrotoluene (DNT), to hepatic DNA by 95% after a single i.p. injection. Activation of DNT to genotoxic metabolites involves enzymes in both the liver and the intestinal flora. Since PCP also has bactericidal activity and induces hepatic mixed function oxidase activity after longer treatment, the effect of PCP on intestinal enzyme activity and the biotransformation of DNT to genotoxic metabolites, after 1, 2, 4, and 5 weeks of treatment, was studied. Male Fischer 344 rats were dosed daily, by gavage, with either 20 mg/kg PCP 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 and tested for mutagenic activity. At 2 and 4 weeks, 6 control and 6 treated animals were sacrificed and nitroreductase, azo reductase, beta-glucuronidase, dechlorinase and dehydrochlorinase activities were analyzed in homogenates of the small intestine, large intestine, and cecum. At 5 weeks, hepatic DNA adduct formation was assayed by the (32)P-postlabeling of DNA. Results of the study indicated that PCP accelerated the biotransformation of DNT to genotoxic metabolites and potentiated the formation of DNT - induced DNA adducts in the liver.