Pharmaceutisch Weekblad

, Volume 7, Issue 2, pp 67–70 | Cite as

Research in the division of toxicology

The importance of reactive intermediates of drug biotransformation in drug toxicity
  • G. J. Mulder


Within the Center for Bio-Pharmaceutical Sciences research on toxicology has its main object in toxification and detoxification of xenobiotics. The pharmacokinetics of sulfation, glucuronidation and other conjugation reactions is studied. Conjugation may prevent tissue damage that is caused by covalent binding of reactive intermediates. Systems for testing the toxicity of such intermediates are being developed, and a similar screening programme is pursued for elucidating the involvement of reactive intermediates in carcinogenesis.


Public Health Internal Medicine Tissue Damage Science Research Screening Programme 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Mulder GJ, Meerman JHN, Van den Goorbergh JAM. Bioactivation of Xenobiotics by Conjugation. In: Paulsen GD, ed. Advances in xenobiotic conjugation chemistry. Am Chem Soc Symp Series (in press).Google Scholar
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    Meerman JHN. Van Doorn ABD, Mulder GJ. Inhibition of sulfate conjugation of N-hydroxy-2-acetylaminofluorene in isolated perfused rat liver and in the ratin vivo by pentachlorophenol and low sulfate. Cancer Res 1980;40:3772–9.PubMedGoogle Scholar
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    Mulder GJ. Weitering JG, Scholtens E, Dawson JR. Pang KS. Extrahepatic sulfation and glucuronidation in the ratin vivo. Determination of the hepatic extraction ratio of harmol and the extrahepatic contribution to harmol conjugation. Biochem Pharmacol 1984:33: 3081–7.PubMedGoogle Scholar
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    Fayz S, Cherry WF, Dawson JR, Mulder GJ, Pang KS. Inhibition of acetaminophen sulfation by 2,6-dichlorophenol (DCNP) in the perfused rat liver preparation. Lack of a compensatory increase of glucuronidation. Drug Metab Dispos 1984;12:323–9.PubMedGoogle Scholar
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    Mulder GJ, Brouwer S, Scholtens E. High-rate intestinal conjugation of 4-methylumbelliferone during intravenous infusion in the ratin vivo. Biochem Pharmacol 1984;33:2341–4.PubMedGoogle Scholar
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    Glazenburg EJ, Jekel-Halsema IMC, Baranczyk-Kuzma A, Krijgsheld KR, Mulder GJ.D-Cysteine as a selective precursor for inorganic sulfate in the ratin vivo. Effect ofD-cysteine on the sulfation of harmol. Biochem Pharmacol 1984;33:625–8.PubMedGoogle Scholar
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    Mulder GJ, Dawson JR, Pang KS. Competition between sulfation and glucuronidation in the ratin vivo. Enzyme kinetics and pharmacokinetics of conjugation. Biochem Soc Trans 1984;12:17–20.PubMedGoogle Scholar
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    Glazenburg EJ, Bruggink JE, Wolters-Keulemans K, Mulder GJ. Inhibition of glutathione efflux in the recirculating rat liver perfusion by cysteine but not by oxothiazolidine carboxylate, an intracellular cysteine precursor. FEBS Letters 1984;178:271–4.PubMedGoogle Scholar
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    Mulder GJ, Kadlubar FF, Mays JB, Hinson JA. Reaction of mutagenic phenacetin metabolites with glutathione and DNA: possible implications for toxicity. Mol Pharmacol 1984;26:342–7.PubMedGoogle Scholar
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    Van Bladeren PJ, Breimer DD, Van Huijgenvoort JATCM, Vermeulen NPE, Van der Gen A. The metabolic formation ofN-acetyl-S-2-hydroxyethyl-L-cysteine from tetradeutero-1,2-dibromoethane. Relative importance of oxidation and glutathione conjugationin vivo. Biochem Pharmacol 1981:30:2499–502.Google Scholar
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    Bisschop A, Bakker O, Meerman JHN, Van Wijk R, Van der Heijden CA, Stavenuiter JFC. Induction of ornithine decarboxylase and augmentation of tyrosine aminotransferase activity byN-hydroxy-2-acetyl-aminofluorene and 2-acetylaminofluorene in rat liver. Influence of sex, retinylacetate, indomethacin, and pentachlorophenol. Cancer Invest 1984;2:267–7.PubMedGoogle Scholar
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    Meerman JHN, Sterenborg HJ, Mulder GJ. Use of pentachlorophenol as long-term inhibitor of sulfation of phenols and hydroxyamic acids in the ratin vivo. Biochem Pharmacol 1983;32:1587–93.PubMedGoogle Scholar

Copyright information

© Bohn, Scheltema & Holkema 1985

Authors and Affiliations

  • G. J. Mulder
    • 1
  1. 1.Center for Bio-Pharmaceutical Sciences, Sylvius LaboratoriesState University of LeidenThe Netherlands

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