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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
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NTIS  PB91-191544 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 14p
Abstract 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.
Supplementary Notes Pub. in Pesticide Biochemistry and Physiology, v39 n2 p168-181 Feb 91. Prepared in cooperation with Environmental Health Research and Testing, Inc., Research Triangle Park, NC. Sponsored by Health Effects Research Lab., Research Triangle Park, NC.
NTIS Title Notes Journal article.
Title Annotations Reprint: Potentiation of 2,6-Dinitrotoluene Genotoxicity in Fischer 344 Rats by Pretreatment with Pentachlorophenol.
Category Codes 57Y; 57F; 68E
NTIS Prices PC A03/MF A01
Primary Description 600/10
Document Type NT
Cataloging Source NTIS/MT
Control Number 119326283
Origin NTIS
Type CAT