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IN VITRO METABOLISM AND DNA ADDUCT FORMATION FROM THE MUTAGENIC ENVIRONMENTAL CONTAMINANT 2-NITROFLURORANTHENE
Citation:
Herreno-Saenz, D., F. Evans, T. Heinze, J. Lewtas, AND P. Fu. IN VITRO METABOLISM AND DNA ADDUCT FORMATION FROM THE MUTAGENIC ENVIRONMENTAL CONTAMINANT 2-NITROFLURORANTHENE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-93/340.
Description:
The metabolism and DNA adduct formation by the mutagenic environmental contaminant 2-nitrofluoranthene (2-NFA) was studied. ncubation under aerobic conditions with liver microsomes of rats pretreated with 3-methylcholanthrene yielded 2-NFA tran-7.8-dihydrodiol, 2-NFA tran-9,10-dihydrodiol, and 7-, 8- and 9-phenolic metabolites. hen the epoxide hydrolase inhibitor, 3,3,3-trichloropropylene (TCPO) was present in the incubation, only phenolic metabolites were detected. nder hypo)dc conditions, 2-aminofluoranthene was obtained, together with a trace of the ring-oxidized metabolites. he activated metabolite, N-hydroxy-2-aminofluoranthene, was prepared in situ and reacted with calf thymus DNA. pon enzymatic hydrolysis of the. NA and purification by HPLC, a C8-substituted deoxyguanosine adduct, N-(deoxyguanosin-8-yl)-2-aminofluoranthene, was identified by mass and proton NMR spectral analysis. his adduct was also formed at a level of 10 pmol/mg DNA when 2-NFA was metabolized by xanthine oxidase, 6 pmol/mg DNA from incubation with liver microsomes of rats pretreated with 3-MC, and 3 pmol/mg DNA from metabolism by liver microsomes of rats pretreated with phenobarbital.