Ciba Foundation Symposium 76 - Environmental Chemicals,

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 effect 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 keen on 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 health and wellbeing examine (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 way of nutritional components (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 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 value of Liver Hypertrophy Produced via Inducers of Drug?Metabolizing Enzymes (pages 261–274): Emmanuel Farber
Chapter 15 The effect of foodstuff 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 compounds on Drug treatment in people: reviews with Contraceptive Steroids (pages 289–306): A.M. Breckenridge, D.J. again, Karen go, Francesca Crawford, M. MacIver, M. L'E Orme, P.H. Rowe and Eileen Smith
Chapter 17 nutrition D Metabolism in sufferers taken care of 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 reviews in people (pages 349–358): John Higginson

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1, the parent compound alone is the ultimate toxic agent responsible for damage to extrahepatic tissue in mechanism ‘A’. The extrahepatic organ in which toxicity develops may depend upon selective exposure, preferential uptake or preferential concentration of the toxic agent in the target tissue, or upon the presence of specific receptors or other highly susceptible sites of action. Alternatively, there may be little selectivity of target organ; the toxic agent may affect the liver as well as many extrahepatic sites.

DNA was isolated and hydrolysed to nucleosides (JernstrBm et al 1980). Hydrolysed D N A was analysed on a reversed phase column (C18) using a methanoVwater gradient. Total benzo[a]pyrene modification of cellular D N A was estimated to be 20 pmoles/mg DNA. (b) Same conditions as above, except that the cells were isolated from phenobarbitone-treated rats and incubated with 20 pM [3H]benzo[a]pyrene for 30 min. Total benzo[a]pyrene modification of cellular DNA was estimated to be 5 pmoles/mg DNA. - and benzo[a]pyrene-7,8-dihydrodiol(retention time 46 minutes) can be identified (cf JernstrOm et a1 1980).

In contrast to the metabolism of carbon tetrachloride and bromobenzene, that of benzo[a]pyrene is affected primarily by 3-methylcholanthreneinduction. As shown in Table 3, pretreatment of rats with this inducer dramatically increases metabolism of benzo[a]pyrene by isolated hepatocytes, whereas pretreatment with phenobarbitone has only a minor effect. 4) containing 2% bovine serum albumin. The benzo[a]pyrene metabolites formed were analysed by high performance liquid chromatography (Burke et al 1977).

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