Content:
Chapter 1 Chairman's advent (pages 1–2):
Chapter 2 The function of the Drug?Metabolizing Enzymes (pages 5–24): James W. Bridges
Chapter three The impression of Inducers on Drug?Metabolizing Enzyme task 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 curious about DNA fix and Mutagenesis (pages 67–81): B. A. Bridges
Chapter 6 Induction of Drug?Metabolizing Enzymes by means of Polycyclic fragrant Hydrocarbons: Mechanisms, and a few Implications in Environmental future health study (pages 83–99): John R. Bend
Chapter 7 Induction of Drug?Metabolizing Enzymes by means of Phenobarbitone: Structural and Biochemical features (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 transformed Porphyrins (pages 119–139): Francesco De Matteis, Anthony H. Gibbs, Lavinia Cantoni and Jean Francis
Chapter nine law of Human Drug Metabolism by means of 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 overseas Compounds on Formation and Disposition of Reactive Metabolites (pages 169–189): F. Oesch
Chapter eleven Pharmacokinetic components Governing the Steady?State Concentrations of overseas 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 value of Liver Hypertrophy Produced through Inducers of Drug?Metabolizing Enzymes (pages 261–274): Emmanuel Farber
Chapter 15 The effect 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 impact of Environmental chemical substances on Drug remedy in people: stories with Contraceptive Steroids (pages 289–306): A.M. Breckenridge, D.J. again, Karen move, 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

Sample text

Gillette: We need to be cautious though, because there can be a species difference in inducibility. For example, the paracetamol toxicity is decreased in hamsters but increased in mice by pretreatment with phenobarbitone (Potter et a1 1974, Mitchell et a1 1973). Cancer Res 39:2971-2977 Cha Y N , Bueding E 1979 Effect of 2(3)-tert-butyl-4-hydroxyanisoleadministration on the activities of several hepatic microsomal and cytoplasmic enzymes in mice. Biochem Pharmacol 28~1917-1921 Gillette JR 1974 Formation of reactive metabolites as a cause of drug toxicity.

4. e. the percentage of cells permeable to NADH as a function of incubation time) (C), in hepatocytes isolated from control, phenobarbitone and 3-methylcholanthrene-pretreatedrats. Hepatocytes were incubated under the conditions described in Fig. 3 legend. 6 mM. Bromobenzene metabolites were measured according to Zampaglione et al(1973). Concentration of GSH and NADH penetration were assayed as described by Thor et a1 (1978). pretreatment with 3-methylcholanthrene produces a less reactive epoxide (bromobenzene-2,3-epoxide) as the major primary metabolite.

When the parent compound alone is the ultimate toxin, metabolic transformations lead invariably to less toxic products (detoxification). Such detoxification reactions may occur in the liver or in the extrahepatic tissues or at both sites. Mechanisms B and hybrid mechanisms. When toxicity is caused by active metabolites, metabolic transformations may produce the ultimate toxic products (by toxification pathways) or less active products (by detoxification pathways). g. an active metabolite is formed initially, and undergoes a second transformation to a less toxic product which can be eliminated from the body).

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