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Main Title In vitro Metabolism and DNA Adduct Formation from the Mutagenic Environmental Contaminant 2-Nitrofluoranthene.
Author Herreno-Saenz, D. ; Evans, F. E. ; Heinze, T. ; Lewtas, J. ; Fu, P. P. ;
CORP Author National Center for Toxicological Research, Jefferson, AR.;Health Effects Research Lab., Research Triangle Park, NC. Genetic Toxicology Div.
Publisher c1992
Year Published 1992
Report Number EPA/600/J-93/340;
Stock Number PB93-229581
Additional Subjects Metabolic activation ; DNA damage ; Mutagens ; Environmental pollutants ; Liquid chromatography ; Rats ; In vitro analysis ; Liver microsomes ; Nuclear magnetic resonance ; Enzyme inhibitors ; Epoxide hydrolases ; Carcinogens ; Mass spectroscopy ; pH ; Reprints ; 2-Nitrofluoranthene
Library Call Number Additional Info Location Last
NTIS  PB93-229581 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 9p
The metabolism and DNA adduct formation by the mutagenic environmental contaminant 2-nitrofluoranthene (2-NFA) was studied. Incubation under aerobic conditions with liver microsomes of rats pretreated with 3-methylcholanthrene yielded trans-7,8-dihydroxy-7,8-dihydro-2-nitrofluoranthene, trans-9,10-dihydroxy-9,10-dihydro-2-nitrofluoranthene, and 7-, 8-, and 9-phenolic metabolites. When the epoxide hydrolase inhibitor, 3,3,3-trichloropropylene was present in the incubation, only phenolic metabolites were detected. Under hypoxic conditions, 2-aminofluoranthene was obtained, together with a trace of the ring-oxidized metabolites. The activated metabolite, N-hydroxy-2-aminofluoranthene, was prepared in situ and reacted with calf thymus DNA. Upon enzymatic hydrolysis of the DNA and purification by HPLC, a C8-substituted deoxyguanosine adduct, N-(deoxyguanosin-8-yl)-2-aminofluoranthene, was identified by mass and proton NMR spectral analysis. This adduct was also formed at a level of 10 pmol/mg of DNA when 2-NFA was metabolized by xanthine oxidase, 6 pmol/mg of DNA from incubation with liver microsomes of rats pretreated with 3-methylcholanthrene, and 3 pmol/mg of DNA from metabolism by liver microsomes of rats pretreated with phenobarbital.