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Chapter 1 Chairman's advent (pages 1–2):
Chapter 2 The position of the Drug?Metabolizing Enzymes (pages 5–24): James W. Bridges
Chapter three The impact of Inducers on Drug?Metabolizing Enzyme job and on Formation of Reactive Drug Metabolites within the Liver (pages 25–42): Sten Orrenius, Hjordis Thor and Bengt Jernstrom
Chapter four results of Inducers and Inhibitors on Drug?Metabolizing Enzymes and on Drug Toxicity in Extrahepatic Tissues (pages 43–66): Michael R. Boyd
Chapter five Induction of Enzymes considering DNA fix and Mutagenesis (pages 67–81): B. A. Bridges
Chapter 6 Induction of Drug?Metabolizing Enzymes by way of Polycyclic fragrant Hydrocarbons: Mechanisms, and a few Implications in Environmental future health examine (pages 83–99): John R. Bend
Chapter 7 Induction of Drug?Metabolizing Enzymes by means of Phenobarbitone: Structural and Biochemical points (pages 101–118): Urs A. Meyer, Peter J. Meier, Hans Hirsiger, Urs Giger and Felix R. Althaus
Chapter eight Substrate?Dependent Irreversible Inactivation of Cytochrome P?450: Conversion of Its Haem Moiety into converted Porphyrins (pages 119–139): Francesco De Matteis, Anthony H. Gibbs, Lavinia Cantoni and Jean Francis
Chapter nine rules of Human Drug Metabolism through nutritional elements (pages 147–167): A.H. Conney, M.K. Buening, E.J. Pantuck, C.B. Pantuck, J.G. Fortner, K.E. Anderson and A. Kappas
Chapter 10 Infiuence of international Compounds on Formation and Disposition of Reactive Metabolites (pages 169–189): F. Oesch
Chapter eleven Pharmacokinetic elements Governing the Steady?State Concentrations of international chemical compounds and Their Metabolites (pages 191–217): James R. Gillette
Chapter 12 Toxicological Implications of Polymorphic Drug Metabolism (pages 219–244): J.C. Ritchie, T.P. Sloan, J.R. Idle and R.L. Smith
Chapter thirteen Immunologically Mediated Toxicity (pages 245–259): H.E. Amos
Chapter 14 Toxicological importance of Liver Hypertrophy Produced by means of Inducers of Drug?Metabolizing Enzymes (pages 261–274): Emmanuel Farber
Chapter 15 The impact of meals and Inducers on Mechanisms of Toxicity in people and Animals (pages 275–288): Andre E.M. McLean, David J. Wltts and Denise Tame
Chapter sixteen impression of Environmental chemical compounds on Drug remedy in people: experiences with Contraceptive Steroids (pages 289–306): A.M. Breckenridge, D.J. again, Karen pass, Francesca Crawford, M. MacIver, M. L'E Orme, P.H. Rowe and Eileen Smith
Chapter 17 diet D Metabolism in sufferers handled with Phenytoin and Phenobarbitone (pages 315–330): J.O. Hunter and M. Davie
Chapter 18 Chemical disorder in people: difficulties in Comparative Toxicology (pages 331–347): Irving J. Selikoff
Chapter 19 Implications for destiny reports in people (pages 349–358): John Higginson

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Extra resources for Ciba Foundation Symposium 76 - Environmental Chemicals, Enzyme Function and Human Disease

Example text

There is some recent evidence that the degree of toxicity produced by phenacetin and by an analogous compound depended on the extent to which each compound was covalently bound. The one that was bound more had much less toxicity. The absence of glutathione in this case could remove protection from other cell functions and other toxicities, like those mediated by lipid peroxidation, which might therefore be more important than covalent binding. What is the evidence that the sequence of events is governed predominantly by the covalent binding of the reactive metabolites; could it be that liver cell necrosis might be more dependent on other sequences of events, like lipid peroxidation, against which glutathione also provides protection?

Once this phenomenon had been recognized, it was utilized for purifying the different forms of cytochrome P-450 (Vatsis & Coon 1978). The effects of most inducers, including phenobarbitone and 3-methylcholanthrene, on the cytochrome P-450 system are usually more pronounced on phase I than on phase I1 reactions. This is often manifested as a change in the ratio between oxygenated, unconjugated and conjugated drug metabolites after induction; the ratio of unconjugated to conjugated metabolites of 7-ethoxycoumarin, in isolated hepatocytes, changed from 30 - S.

In the induced system, the metabolism of bromobenzene is rapid and presumably proceeds by way of formation of reactive intermediate(s). In the case of paraquat, which we have also studied, we have not seen a comparable effect on pyridine nucleotide concentrations, or on redox states of the pyridine nucleotide. Davies; The depletion of nucleotides demonstrated by Smith et a1 (1979) was in the lung rather than in the hepatocyte. Farber; I think we ought to distinguish clearly between cell damage and cell death.

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