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The in vitro/in vivo comparative metabolism of 4-aminobiphenyl using isolated hepatocytes

  • Original Investigations
  • Metabolism of Xenobiotics
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Abstract

The metabolism of 4-aminobiphenyl by isolated hepatocytes from various species was compared with urinary metabolite profiles in the same species. Radioactive compounds in concentrates of ether extracts from hepatocytes or urine following hydrolysis were analysed by TLC and reversed phase HPLC in conjunction with radioactivity monitoring and synthetic standards.

The major metabolites from hepatocytes and in urine were 4-acetamidobiphenyl, 3-hydroxy-4-aminobiphenyl 4′-hydroxy-4-aminobiphenyl and 4′-hydroxy-4-acetamidobiphenyl. Oxidation of the amine nitrogen gave hydroxylamino, nitroso and nitro compounds. Minor metabolites were 2′-hydroxy amine and amide, the hydroxamic acid and the oxamic acid. The urinary metabolite profiles correlated well with those from hepatocytes for each species.

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Abbreviations

4-ABP:

4-aminobiphenyl

AA:

4-acetamidobiphenyl

A3-OH:

3-hydroxy-4-aminobiphenyl

A4′-OH:

4′-hydroxy-4-aminobiphenyl

A2′-OH:

2-hydroxy-4-aminobiphenyl

AA4′-OH:

4′-hydroxy-4-acetamidobiphenyl

AA3-OH:

3-hydroxy-4-acetamidobiphenyl

AA2′-OH:

2′-hydroxy-4-acetamidobiphenyl

AAN-OH:

N-hydroxy-4-acetamidobiphenyl

NBP:

4-nitrobiphenyl

AN-OH:

4-hydroxylaminobiphenyl

NOBP:

4-nitrosobiphenyl

References

  • Billings RE, McMahon RE, Ashmore J, Wagle SR (1977) The metabolism of drugs in isolated rat hepatocytes. Drug Metab Dispos 5: 518–526

    Google Scholar 

  • Booth J, Boyland E (1964) Enzymatic N-hydroxylation of arylamines and conversion of aryl hydroxylamines into o-aminophenols. Biochem J 91: 362–369

    Google Scholar 

  • Corbett MD, Chikpo BR (1979) Quantitative determination of Narylaceto- and N-arylglycolhydroxamic acids in biochemical mixtures. Anal Biochem 98: 169–177

    Google Scholar 

  • Fries W, Kiese M, Lenk W (1973) Oxidation of polycyclic N-arylacetamides to glycolamides and hydroxamic acids in rabbits. Xenobiotica 3: 525–540

    Google Scholar 

  • Fry JR, Jones CA, Wiebkin P, Belleman R, Bridges JW (1976) The enzymatic isolation of adult rat hepatocytes in a functional and viable state. Anal Biochem 71: 341–350

    Google Scholar 

  • Gorrod JW (1979) The metabolism and mode of action of some aromatic amines in relation to carcinogenesis. Ph D Thesis, University of London

  • Howard RB, Lee JC, Pesch LA (1973) The preparation of rat liver parenchymal cells by improved enzymatic techniques. J Cell Biol 57: 642–658

    Google Scholar 

  • Masson HA, Ioannides C, Gorrod JW, Gibson GG (1983) The role of highly purified cytochrome P-450 isozymes in the activation of 4-aminobiphenyl to mutagenic products in the Ames test. Carcinogenesis 4: 1583–1586

    Google Scholar 

  • McMahon RE, Turner JC, Whitaker GW (1980) The N-hydroxylation and ring-hydroxylation of 4-aminobiphenyl in vitro by hepatic monooxygenases from rat, mouse, hamster, rabbit and guinea-pig. Xenobiotica 10: 469–481

    Google Scholar 

  • Miller EC, Sandin RB, Miller JA, Rusch HP (1956) The carcinogenicity of compounds related to 2-acetylamino fluorence III aminobiphenyl and benzidine. Cancer Res 16: 525–534

    Google Scholar 

  • Miller JA, Wyatt CS, Miller EC, Hartmann HA (1961) The N-hydroxylation of 4-acetylaminobiphenyl by the rat and dog and the strong carcinogenicity of N-hydroxy-4-acetylaminobiphenyl in the rat. Cancer Res 21: 1465–1478

    Google Scholar 

  • Raiford LC, Clark EP (1926) Behaviour of mixed O-acyl-N-acyl dervatives in which the reacting groups are not on adjacent carbon atoms. J Am Chem Soc 48: 483–489

    Google Scholar 

  • Seglen PO (1973) Preparation of rat liver cells; enzymatic requirements for tissue dispersal. Exp Cell Res 82: 391–398

    Google Scholar 

  • Uehleke H (1963) N-Hydroxylation of carcinogenic amines in vivo and in vitro with liver microsomes. Biochem Pharmacol 12:219–221

    Google Scholar 

  • Uehleke H, Nestel K (1967) Hydroxylaminobiphenyl and nitroso biphenyl: biological oxidation products of 4-aminobiphenyl and reduction metabolites of 4-nitrobiphenyl. Arch Pharmacol Exp Pathol 257: 151–171

    Google Scholar 

  • Wiebkin P, Fry JR, Jones CA, Lowing R, Bridges JW (1978) Biphenyl metabolism in isolated rat hepatocytes: effect of induction and nature of the conjugates. Biochem Pharmacol 27: 1899–1907

    Google Scholar 

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Authors and Affiliations

  1. Chelsea Department of Pharmacy, King's College London (KQC), University of London, Manresa Road, SW3 6LX, London, UK

    S. D. Jatoe & J. W. Gorrod

Authors
  1. S. D. Jatoe
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  2. J. W. Gorrod
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Dedicated to Professor Dr. med. Herbert Remmer on the occasion of his 65th birthday

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Jatoe, S.D., Gorrod, J.W. The in vitro/in vivo comparative metabolism of 4-aminobiphenyl using isolated hepatocytes. Arch Toxicol 60, 65–68 (1987). https://doi.org/10.1007/BF00296949

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  • DOI: https://doi.org/10.1007/BF00296949

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