Download Ciba Foundation Symposium 76 - Environmental Chemicals, PDF
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 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 desirous about DNA fix and Mutagenesis (pages 67–81): B. A. Bridges
Chapter 6 Induction of Drug?Metabolizing Enzymes via Polycyclic fragrant Hydrocarbons: Mechanisms, and a few Implications in Environmental overall healthiness learn (pages 83–99): John R. Bend
Chapter 7 Induction of Drug?Metabolizing Enzymes via 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 changed Porphyrins (pages 119–139): Francesco De Matteis, Anthony H. Gibbs, Lavinia Cantoni and Jean Francis
Chapter nine rules 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 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 substances 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 effect of Environmental chemical substances on Drug treatment 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 taken care of with Phenytoin and Phenobarbitone (pages 315–330): J.O. Hunter and M. Davie
Chapter 18 Chemical sickness in people: difficulties in Comparative Toxicology (pages 331–347): Irving J. Selikoff
Chapter 19 Implications for destiny experiences 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
I also have a point about carbon tetrachloride. We have shown that if cysteine is given in vivo, protection against carbon tetrachloride does not occur (unpublished work). We found in liver cells that chelating agents will completely block lipid peroxidation, but the damage by paracetamol is not altered. O mM carbon tetrachloride and 20-90 FM benzo[a]pyrene. Further, I cannot claim that the isolated hepatocyte system represents the normal physiological situation. Our system for studying toxicity has, however, several advantages.
However, many toxic effects are now known to be due to formation of reactive metabolites, while the parent compound is usually biologically inert. This is analogous to results on major chemical carcinogens whose behaviour originally led to the concept of metabolic activation (Miller & Miller 1973). Fig. 2 shows a scheme of metabolic activation and inactivation of en- - METABOLIC ACTIVATION AND I N A C T I V A T I O N NADPH, o 2 Reactive oxygenated Substrate I Cyt p - 4 5 0 intermediate, free radicals Stable oxygenated product 1 Nucleophilic attack of: GSII, c y s t e i n e c o f a c t o r SH and nitrogen p r o t e i n SH, nucleic acid oxygen and n i t r o gen atoms, e t c V Formation o f conjugates: glucuronides, sulphates, mercapturic acids, etc w FIG.
An increase in hepatic microsomal 21 ENZYME INDUCERS, DRUG METABOLISM AND TOXICITY cytochrome P-450 was also produced by pretreatment of rats with 3-methylcholanthrene (Orrenius 1965). Detailed experiments subsequently revealed that the increase in haemoprotein concentration could be attributed to a form of cytochrome P-450 that had characteristic properties of light absorption and catalysis (Kuntzman et a1 1968), and multiple forms of hepatic cytochrome P-450 have now been isolated (cf Lu et a1 1971, Vatsis & Coon 1978).