2-Acetylaminofluorene metabolism in rat liver microsomes

Formation of 9-hydroxy-2-acetylaminofluorene and effect of hepatic enzyme modifiers

Ock Soon Son, John W. Fowble, Duane Miller, Dennis R. Feller

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

9-Hydroxy-2-acetylaminofluorene [N-(9-hydroxy-9H-fluoren-2-yl)acetamide; 9-OH-2-AAF] was isolated and identified as a metabolite of 2-acetylaminofluorene (2-AAF) in rat liver microsomes. Evidence for this metabolite was provided by thin-layer chromatography (tlc), inverse isotope dilution analysis, pH partition, and nmr spectroscopic studies. 9-Oxo-2-acetylaminofluorene [N-(9-oxo-9H-fluoren-2-yl)acetamide; 9-OXO-2-AAF] was also detected and identified (by tlc) as a microsomal metabolite of 2-AAF. Microsomal conversion of 2-AAF to 9-OH-2-AAF and 9-OXO-2-AAF was dependent upon the presence of NADPH and was inhibited by a carbon monoxide atmosphere. Increased formation of 9-OH-2-AAF was noted in microsomes obtained from rats treated with the hepatic enzyme modifiers, phenobarbital and pregnenolone-16α-carbonitrile and inhibited in the presence of metyrapone. In contrast, treatment with 3-methylcholanthrene or chlordane did not modify 9-OH-2-AAF or 9-OXO-2-AAF formation. Also, rates of 9-OXO-2-AAF formation were increased only by prior administration of phenobarbital and were unaffected by metyrapone. These data provide evidence for the involvement of specific types of cytochrome P-450 in the 9-carbon hydroxylation reaction of 2-AAF.

Original languageEnglish (US)
Pages (from-to)367-377
Number of pages11
JournalToxicology and Applied Pharmacology
Volume51
Issue number2
DOIs
StatePublished - Jan 1 1979
Externally publishedYes

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2-Acetylaminofluorene
Liver Microsomes
Metabolism
Liver
Rats
Enzymes
Metabolites
Metyrapone
Thin layer chromatography
Phenobarbital
Thin Layer Chromatography
Pregnenolone Carbonitrile
Chlordan
Hydroxylation
Methylcholanthrene
Carbon Monoxide
Microsomes
Atmosphere
NADP
Isotopes

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

Cite this

2-Acetylaminofluorene metabolism in rat liver microsomes : Formation of 9-hydroxy-2-acetylaminofluorene and effect of hepatic enzyme modifiers. / Son, Ock Soon; Fowble, John W.; Miller, Duane; Feller, Dennis R.

In: Toxicology and Applied Pharmacology, Vol. 51, No. 2, 01.01.1979, p. 367-377.

Research output: Contribution to journalArticle

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abstract = "9-Hydroxy-2-acetylaminofluorene [N-(9-hydroxy-9H-fluoren-2-yl)acetamide; 9-OH-2-AAF] was isolated and identified as a metabolite of 2-acetylaminofluorene (2-AAF) in rat liver microsomes. Evidence for this metabolite was provided by thin-layer chromatography (tlc), inverse isotope dilution analysis, pH partition, and nmr spectroscopic studies. 9-Oxo-2-acetylaminofluorene [N-(9-oxo-9H-fluoren-2-yl)acetamide; 9-OXO-2-AAF] was also detected and identified (by tlc) as a microsomal metabolite of 2-AAF. Microsomal conversion of 2-AAF to 9-OH-2-AAF and 9-OXO-2-AAF was dependent upon the presence of NADPH and was inhibited by a carbon monoxide atmosphere. Increased formation of 9-OH-2-AAF was noted in microsomes obtained from rats treated with the hepatic enzyme modifiers, phenobarbital and pregnenolone-16α-carbonitrile and inhibited in the presence of metyrapone. In contrast, treatment with 3-methylcholanthrene or chlordane did not modify 9-OH-2-AAF or 9-OXO-2-AAF formation. Also, rates of 9-OXO-2-AAF formation were increased only by prior administration of phenobarbital and were unaffected by metyrapone. These data provide evidence for the involvement of specific types of cytochrome P-450 in the 9-carbon hydroxylation reaction of 2-AAF.",
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AB - 9-Hydroxy-2-acetylaminofluorene [N-(9-hydroxy-9H-fluoren-2-yl)acetamide; 9-OH-2-AAF] was isolated and identified as a metabolite of 2-acetylaminofluorene (2-AAF) in rat liver microsomes. Evidence for this metabolite was provided by thin-layer chromatography (tlc), inverse isotope dilution analysis, pH partition, and nmr spectroscopic studies. 9-Oxo-2-acetylaminofluorene [N-(9-oxo-9H-fluoren-2-yl)acetamide; 9-OXO-2-AAF] was also detected and identified (by tlc) as a microsomal metabolite of 2-AAF. Microsomal conversion of 2-AAF to 9-OH-2-AAF and 9-OXO-2-AAF was dependent upon the presence of NADPH and was inhibited by a carbon monoxide atmosphere. Increased formation of 9-OH-2-AAF was noted in microsomes obtained from rats treated with the hepatic enzyme modifiers, phenobarbital and pregnenolone-16α-carbonitrile and inhibited in the presence of metyrapone. In contrast, treatment with 3-methylcholanthrene or chlordane did not modify 9-OH-2-AAF or 9-OXO-2-AAF formation. Also, rates of 9-OXO-2-AAF formation were increased only by prior administration of phenobarbital and were unaffected by metyrapone. These data provide evidence for the involvement of specific types of cytochrome P-450 in the 9-carbon hydroxylation reaction of 2-AAF.

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