Front Cover

Microsomes and Drug Oxidations

Copyright Page

Table of Contents

LIST OF PARTICIPANTS

PREFACE

PART I: BIOCHEMISTRY

CHAPTER 1. LIPID STRUCTURE OF LIVER MICROSOMAL MEMBRANES, LIMITATIONS OF A MODEL

SUMMARY

RIGID AND FLUID AREAS IN LIVER MICROSOMES

BOUNDARY LIPID AND THE CYTOCHROME P-450 COMPLEX

PROSPECTS; MICROSOMAL MEMBRANES - A MULTIPHASE SYSTEM,LIMITATIONS OF A MODEL

REFERENCES

CHAPTER 2. INTERACTIONS BETWEEN CYTOCHROME P-450 AND NADPH CYTOCHROMEP-450 REDUCTASE IN THE MICROSOMAL MEMBRANE

Organizational Models of the Monooxygenase Enzymes

Chemical Modification Studies

Incorporation of Purified Cytochrome P-450 into the Microsomal Membrane

Effect of Temperature on Monooxygenase Reactions

Requirements of a Nonrigid Model

Acknowledgments

References

CHAPTER 3. A STUDY OF CYTOCHROME P-450 REDUCTION BY SODIUM DITHIONITE

ABSTRACT

INTRODUCTION

MATERIALS AND METHODS

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 4. INVESTIGATION OF MICROSOMAL HYDROXYLATING SYSTEM AT SUB-ZERO TEMPERATURES

INTRODUCTION

RESULTS

CONCLUSION

ACKNOWLEDGEMENTS

REFERENCES

CHAPTER 5. ISOLATION OF MICROSOMAL ELECTRON TRANSPORT COMPONENTS AND RECONSTITUTION OF THE ELECTRON TRANSFER ACTIVITY ON LIPOSOMAL VESICLES

ABSTRACT

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

ACKNOWLEDGEMENTS

REFERENCES

CHAPTER 6. DIFFERENCES IN SUBSTRATE AFFINITY AND CATALYTIC SPECIFICITY OF INDUCIBLE AND NON-INDUCIBLE FORMS OF CYTOCHROME P-450 IN RABBIT LIVER

REFERENCES

CHAPTER 7. EFFECTS OF BUFFER COMPOSITION ON THE LOW-SPIN ESR SPECTRUM OF CYTOCHROME P-450

ABSTRACT

INTRODUCTION

MATERIALS AND METHODS

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 8. KINETICS OF TIAMUTINR INTERACTION WITH CYTOCHROME P–450 FROM RABBIT LIVER

ABSTRACT

INTRODUCTION

MATERIALS AND METHODS

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 9. DIFFERENT PHASES OF HYDROXYLASE INDUCTION IN LIVER MICROSOMES OF FEMALE MICE DURING INHALATION OF CYCLOHEXANE AND D,L-CAMPHOR

ABSTRACT

INTRODUCTION

METHODS

RESULTS

DISCUSSION

ACKNOWLEDGMENT

REFERENCES

CHAPTER 10. PROTEIN-LIPID INTERACTIONS IN THE LIVER MICROSOMAL HYDROXYLASE SYSTEM

ABSTRACT

INTRODUCTION

INTERACTIONS OF PURIFIED DELIPIDATED P-450 WITH PC

INTERACTIONS OF THE P-450-DEPENDENT HYDROXYLASE SYSTEM WITH PC AND NEUTRAL FATS

BINDING OF TRITON X-100 TO CYT0CHR0ME P-450

ACKNOWLEDGEMENTS

REFERENCES

CHAPTER 11. FURTHER STUDIES OF THE FLUROXENE MEDIATED DESTRUCTION OF HEPATIC MICROSOMAL CYTOCHROMES P-450 IN VITRO

ABSTRACT

INTRODUCTION

EXPERIMENTAL

RESULTS AND DISCUSSION

REFERENCES

ACKNOWLEDGEMENTS

CHAPTER 12. PURIFICATION OF MEMBRANE-BOUND OXYGENASES: ISOLATION OF TWO ELECTROPHORETICALLY HOMOGENEOUS FORMS OF LIVER MICROSOMAL CYTOCHROME P-450

ABSTRACT

INTRODUCTION

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 13. MICROSOMAL HEMEPROTEINS P-450LM-2 AND P-450 LM-4:COMPARATIVE STRUCTURAL STUDIES

ABSTRACT

INTRODUCTION

REFERENCES

CHAPTER 14. HEPATIC MICROSOMAL ETHANOL OXIDIZING SYSTEM: ISOLATION AND RECONSTITUTION

ABSTRACT

REFERENCES

CHAPTER 15. CHARACTERIZATION OF NADPH-CYTOCHROME c(P-450) REDUCTASE PURIFIED BY BIOSPECIFIC AFFINITY CHROMATOGRAPHY UTILIZING SPECTROPHOTOMETRIC AND ELECTRON PARAMAGNETIC RESONANCE TECHNIQUES

ABSTRACT

INTRODUCTION

METHODS

RESULTS

DISCUSSION

REFERENCES

CHAPTER 16. RELATIONSHIP BETWEEN THE MEMBRANE LIPIDS AND SUBSTRATE-CYTOCHROME P-450 BINDING REACTION IN BOVINE ADRENO-CORTICAL MICROSOMES

ABSTRACT

INTRODUCTION

METHODS

RESULTS

DISCUSSION

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 17. KINETIC AND SPECTRAL EVIDENCE FOR MULTIPLE SPECIES OF CYTOCHROME P-450 IN LIVER MICROSOMES

MATERIALS AND METHODS

RESULTS

REFERENCES

CHAPTER 18. DIFFERENCES IN THE INTERACTIONS OF R AND S WARFARIN WITH HEPATIC MICROSOMAL CYTOCHROME P-450

ABSTRACT

INTRODUCTION

EXPERIMENTAL PROCEDURE

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 19. MULTIPLE FORMS OF HOUSEFLY CYTOCHROME P-4501

ABSTRACT

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 20. CATALYTIC HYDROXYLATION ACTIVITIES AND SOME OTHER PROPERTIES OF PARTIALLY PURIFIED RABBIT PULMONARY MICROSOMAL CYTOCHROME P-450

ABSTRACT

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 21. HEPATIC MICROSOMAL AND SOLUBILIZED MIXED-FUNCTION OXIDASE SYSTEMS FROM THE LITTLE SKATE, Raja erznacea, A MARINE ELASMOBRANCH

ABSTRACT

INTRODUCTION

METHODS

RESULTS

DISCUSSION

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 22. AMINIMIDE POLYMERS AS SUPPORTS FOR AFFINITY CHROMATOGRAPHY,UNDER LOW AND HIGH PRESSURE, OF MICROSOMAL ENZYMES

ABSTRACT

INTRODUCTION

MATERIALS AND METHODS

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 23. SEX DIFFERENCES IN THE PATTERN OF CYTOCHROMES P-450 IN RAT LIVER MICROSOMES

ABSTRACT

INTRODUCTION

METHODS

RESULTS

DISCUSSION

ACKNOWLEDGEMENTS

REFERENCES

CHAPTER 24. CHARACTERIZATION OF MULTIPLE FORMS OF HIGHLY PURIFIED CYTOCHROME P-450 FROM THE LIVER MICROSOMES OF RATS, MICE AND RABBITS

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

Acknowledgements

References

CHAPTER 25. THE MECHANISM OF CYTOCHROME P450 ACTION

INTRODUCTION

THE STRUCTURE OF CYTOCHROME P450 AND ITS REACTIONS WITH SUBSTRATES

THE REDUCTION OF THE CYTOCHROME P450-SUBSTRATE COMPLEX

THE FORMATION OF THE ACTIVE OXYGEN COMPLEX

THE MONOOXYGENATION OF THE SUBSTRATE

UNCOUPLED MONOOXYGENATIONS

REFERENCES

CHAPTER 26. OXYGEN REACTIONS OF THE P450 HEME PROTEIN

REFERENCES

CHAPTER 27. THE PEROXIDASE NATURE OFCYTOCHROME P450

ABSTRACT

INTRODUCTION

MATERIALS & METHODS

RESULTS

REFERENCES

ACKNOWLEDGEMENTS

CHAPTER 28. CYTOCHROME P450 CATALYZED OXENE TRANSFER FROM VARIOUS DONORS

ABSTRACT

INTRODUCTION

METHODS

RESULTS

DISCUSSION

ACKNOWLEDGEMENT

REFERENCES

CHAPTER 29. ASSOCIATION ON TYPE I, TYPE II,AND REVERSE TYPE I DIFFERENCE SPECTRA WITH ABSOLUTE SPIN STATE OF CYTOCHROME P-450 IRON

ABSTRACT

INTRODUCTlON

METHODS

RESULTS AND DISCUSSION

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 30. NMR RELAXATION TIME STUDIES OFSUBSTRATE INTERACTIONS WITH P450 AND OTHER HEMOPROTEINS

ABSTRACT

INTRODUCTION

EXPERIMENTAL

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 31. THE INTERACTION OF POLYHALOGENATED METHANES WITH FERROUS CYTOCHROME P450

ABSTRACT

INTRODUCTION

METHODS

RESULTS

DISCUSSION

ACKNOWLEDGEMENTS

REFERENCES

CHAPTER 32. SUBSTRATE-ELICITED DISSOCIATION OF THE ISOSAFROLE METABOLITE-CYTOCHROME P-450 COMPLEX AND THE CONSEQUENTIAL REACTIVATION OF MONOOXYGENATION

ABSTRACT

INTRODUCTION

MATERIALS AND METHODS

RESULTS AND DISCUSSION

ACKNOWLEDGEMENTS

REFERENCES

CHAPTER 33. THE INTERACTION OF HALOTHANE WITH LIVER MICROSOMAL CYTOCHROME P450

ABSTRACT

INTRODUCTION

METHODS

RESULTS

DISCUSSION

ACKNOWLEDGEMENTS

REFERENCES

CHAPTER 34. THE FORMATION OF HYDROGEN PEROXIDE DURING HEPATIC MICROSOMAL ELECTRON TRANSPORT REACTIONS

ABSTRACT

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 35. OXYGEN TRANSFER IN MICROSOMALOXIDATIVE DESULFURATION

ABSTRACT

INTRODUCTION

METHODS

RESULTS

CONCLUSIONS

REFERENCES

CHAPTER 36. REDOX AND LIGAND DYNAMICS IN P450 cam-PUTIDAREDOXIN COMPLEXES

PUTIDAREDOXIN-P450 REDOX DYNAMICS

ROLE OF PD-P450 COMPLEX IN REDOX AND LIGAND DYNAMICS

OTHER P450 INTERMEDIATES INVOLVED IN HYDROXYLATION

REFERENCES

CHAPTER 37. THE INHIBITION OF MIXED-FUNCTION OXIDATION REACTIONS BY AMPHETAMINES IN LIVER AND LUNG MICROSOMES

ABSTRACT

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

ACKNOWLEDGEMENTS

REFERENCES

CHAPTER 38. THE PHYSIOLOGICAL IMPLICATIONS OF DRUG OXIDATIONS TO THE CELL

REFERENCES

CHAPTER 39. NICOTINAMIDE NUCLEOTIDE SYSTEMS AND DRUG OXIDATION IN THE LIVER CELL

ABSTRACT

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

ACKNOWLEDGEMENTS

REFERENCES

CHAPTER 40. THE ROLE OF REDUCING EQUIVALENTS GENERATED IN MITOCHONDRIA IN HEPATIC MIXED-FUNCTION OXIDATION1

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 41. DESTRUCTION OF CYTOCHROME P-450 BY LINOLEIC ACID HYDROPEROXIDE

ABSTRACT

INTRODUCTION

METHODS

RESULTS

DISCUSSION

REFERENCES

CHAPTER 42. STOICHIOMETRY OF OXYGEN UPTAKE, NADPH OXIDATION AND ETHYLMORPHINE N-DEMETHYLATION BY HEPATIC MICROSOMES

ABSTRACT

INTRODUCTION

MATERIALS AND METHODS

RESULTS

DISCUSSION

REFERENCES

CHAPTER 43. STRUCTURAL AND FUNCTIONAL INTERACTION OF ROUGH ENDOPLASMIC RETICULUM (RER) AND MITOCHONDRIA DURING SYNTHESIS OF HEPATIC CYTOCHROME P450

ABSTRACT

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 44. MECHANISM OF N-OXIDE FORMATION BY HEPATIC MIXED FUNCTION OXIDASES

ABSTRACT

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

ACKNOWLEDGEMENTS

REFERENCES

CHAPTER 45. A PRELIMINARY COMPARATIVE STUDY ON THE INFLUENCE OF CYSTEAMINE AND METYRAPONE ON MIXED-FUNCTION OXYGENASE ACTIVITIES IN VARIOUSLY PRETREATED LIVER MICROSOMES FROM RATS AND MICE

ABSTRACT

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

ACKNOWLEDGEMENT

REFERENCES

CHAPTER 46. INHIBITION OF RAT LIVER MICROSOMAL DT DIAPHORASE BY BENZO (a) PYRENE METABOLITE (S)

ABSTRACT

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 47. CHARACTERISTICS OF THE HEPATIC MONOOXYGENASE CATALYZING THE METABOLISM OF PROSTAGLANDIN Ai (PGAi) IN GUINEA PIGS AND RATS I EFFECTS OF INDUCERS

SUMMARY

INTRODUCTION

MATERIALS AND METHODS

RESULTS AND DISCUSSION

ACKNOWLEDGEMENT

REFERENCES

CHAPTER 48. STUDIES ON A CYTOCHROME P-450-DEPENDENT HYDROXYLASE SYSTEM ACTIVE ON STEROIDS IN Bacillus megaterium

ABSTRACT

INTRODUCTION

MATERIALS AND METHODS

RESULTS

DISCUSSION

ACKNOWLEDGEMENTS

REFERENCES

PART II: PHARMACOLOGY

CHAPTER 49. IMPACT OF DRUG MONOXYGENASES IN CLINICAL PHARMACOLOGY

I. INTER-INDIVIDUAL DIFFERENCES IN DRUG RESPONSE

II PLASMA CONCENTRATIONS OF DRUGS

III CLINICAL TOXICOLOGY

CONCLUSIONS

ACKNOWLEDGEMENTS

REFERENCES

CHAPTER 50. THE ROLE OF LIVER NUCLEI IN THE FORMATION OF DNA BINDING PRODUCTS FROM BENZO (a) PYRENE

ACKNOWLEDGEMENT

REFERENCES

CHAPTER 51. MECHANISM OF MICROSOMAL ACTIVATION OF BENZO[a] PYRENE TO DIOL-EPOXIDES:THE SEPARATION AND CHARACTERIZATION OF INTERMEDIATES AND PRODUCTS

ABSTRACT

INTRODUCTION

MATERIALS AND METHODS

RESULTS

DISCUSSION

REFERENCES

CHAPTER 52. THE METABOLISM OF BENZO[a]PYRENE IN CELL CULTURES AND HOMOGENATES FROM DIFFRENT HUMAN FETAL TISSES

ABSTRACT

INTRODUCTION

MATERIALS AND METHODS

RESULTS AND DISCUSSION

CHAPTER 53. ARYL HYDROCARBON HYDROXYLASE IN CULTURED HUMAN LYMPHOCYTES1

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 54. ASSIGNMENT OF A HUMAN GENE FOR ARYL HYDROCARBON HYDROXYLASE EXPRESSION TO CHROMOSOME 2

ABSTRACT

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

ACKNOWLEDGEMENT

REFERENCES

CHAPTER 55. OXIDATIVE METABOLISM OF CARCINOGENS BY TROUT LIVER RESULTING IN PROTEIN BINDING AND MUTAGENICITY

ABSTRACT

INTRODUCTION

MATERIALS AND METHODS

RESULTS

DISCUSSION

REFERENCES

CHAPTER 56. DRUG-DRUG INTERACTIONS VIA INHIBITION OF MICROSOMAL ENZYMES INVOLVED IN METABOLISM OF EPOXIDES PRODUCED BY MICROSOMAL MONOOXYGENASE

SUMMARY

INTRODUCTION

INACTIVATION OF MUTAGENS PRODUCED FROM BENZO(A)PYRENE BY EPOXIDE HYDRATASE

DRUG-DRUG INTERACTIONS VIA INHIBITION OF EPOXIDE HYDRATASE

REFERENCES

CHAPTER 57. LEVELS OF GLUTATHIONE AND GLUTATHIONE-METABOLIZING ENZYMES IN RAT LUNG

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

ACKNOWLEDGMENT

REFERENCES

CHAPTER 58. THE DISPOSITION OF BENZO(A) PYRENE IN ISOLATED PERFUSED RAT LUNG

INTRODUCTION

MATERIAL AND METHODS

RESULTS

DISCUSSION

ACKNOWLEDGEMENTS

REFERENCES

CHAPTER 59. EPOXIDE HYDRATASE IN RAT LUNG

INTRODUCTION

METHODS AND RESULTS

DISCUSSION

ACKNOWLEDGMENT

REFERENCES

CHAPTER 60. MONOOXYGENASE CATALYZED ACTIVATION OF THIONO-SULFUR CONTAINING COMPOUNDS TO REACTIVE INTERMEDIATES

REFERENCES

CHAPTER 61. STIMULATORY EFFECTS OF POLYCHLORINATED BIPHENYLS (PCB) ON CYTOCHROMES P-450 AND P-448 MEDIATED MICROSOMAL OXIDATIONS

SUMMARY

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 62. DEPRESSION OF HEPATIC CYTOCHROME P-450-DEPENDENT MONOOXYGENASE SYSTEMS WITH ADMINISTERED INTERFERON INDUCING AGENTS

ABSTRACT

INTRODUCTION

DISCUSSION

REFERENCES

CHAPTER 63. ALTERATIONS OF HEPATIC MICROSOMAL MIXED FUNCTION OXYGENASE DEPENDENT H2O2 FORMATION DUE TO "UNCOUPLING" AND INDUCTION AS DEMONSTRATED IN VIVO BY ELIMINATION KINETICS OF ETHANOL IN GUINEA PIG

ABSTRACT

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 64. THE MICROSOMAL METABOLISM OF CARCINOGENIC AND/OR THERAPEUTIC HYDRAZINES

ABSTRACT

INTRODUCTION

MATERIALS

METHODS

RESULTS AND DISCUSSION

ACKNOWLEDGEMENTS

References

CHAPTER 65. ROLE OF HYDROXYLATED METABOLITES OF PHENYTOIN IN DOSE-DEPENDENCY

INTRODUCTION

MATERIALS AND METHODS

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 66. SPECIES DIFFERENCES IN DRUG METABOLISM; IN VIVO PARAMETERS OF HEPATIC DRUG-METABOLISING ENZYME ACTIVITY IN THE BABOON

ABSTRACT

INTRODUCTION

METHODS

RESULTS

CONCLUSION

REFERENCES

CHAPTER 67. EVIDENCE FOR BINDING OF LIDOCAINE TO TWO CATALYTICALLY DIFFERENT SITES OF LIVER MICROSOMAL CYTOCHROME P-450

ABSTRACT

INTRODUCTION

MATERIALS AND METHODS

RESULTS

DISCUSSION

ACKNOWLEDGEMENTS

REFERENCES

CHAPTER 68. DIFFERENTIAL INFLUENCE OF PHYSIOLOGICAL, PHARMACOLOGICAL AND PATHOLOGICAL ALTERATIONSON HEPATIC AND EXTRAHEPATIC DRUG METABOLISM

SUMMARY

INTRODUCTION

METHODS

RESULTS

DISCUSSION

REFERENCES

CHAPTER 69. METABOLISM OF HEXOBARBITAL ENANTIOMERS AND INTERACTION WITH CYTOCHROME P-450 IN MALE AND FEMALE MICE AND RATS

ABSTRACT

INTRODUCTION

MATERIAL AND METHODS

RESULTS

DISCUSSION

ACKNOWLEDGEMENTS

REFERENCES

CHAPTER 70. THE MECHANISM OF DEGRADATION OF ENDOGENOUS HEME AND CYTOCHROME P-450 BY HEME OXYGENASE

ABSTRACT

INTRODUCTION

DISCUSSION

REFERENCES

CHAPTER 71. INDUCTION OF CYTOCHROME P-448 BY3-METHYLCHOLANTHRENE IN THERAT DURING INHIBITION OF PROTEINSYNTHESIS IN VIVO

ABSTRACT

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

REFERENCES

ACKNOWLEDGEMENTS

CHAPTER 72. STIMULATION OF LIVER GROWTH ANDMIXED-FUNCTION OXIDASE BY α-HEXACHLOROCYCLOHEXANE:SEPARATION OF INDUCTIVE PATHWAYS

ABSTRACT

INTRODUCTION

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 73. INDUCTION OF CYTOCHROME P-450 BY LONG-TERM INFUSION OF PHENOBARBITAL

ABSTRACT

INTRODUCTION

METHODS

RESULTS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 74. METABOLISM AND MUTAGENICITY OF 2-ACYLAMINOFLUORENES AND RELATED COMPOUNDS

ABSTRACT

INTRODUCTION

MATERIALS AW METHOVS

RESULTS AM0 VISCUSSION

REFERENCES

CHAPTER 75. IN VIVO PARAMETERS OF DRUGMETABOLISM–DIFFERENCES IN SPECIFICITY TOWARDS INDUCING AGENTS

ABSTRACT

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 76. STUDIES ON THE MECHANISM BY WHICH DISULFIRAM AND DIETHYLDITHIOCARBAMATE AFFECT DRUG METABOLISM

ABSTRACT

INTRODUCTION

MATERIALS AND METHODS

RESULTS

DISCUSSION

REFERENCES

CHAPTER 77. ALTERATIONS IN THE ACTIVITIES OF DRUG METABOLIZING ENZYMES INRAT LIVER MICROSOMES BY DIETARY AND IN VITRO INCORPORATED CHOLESTEROL

ABSTRACT

INTRODUCTION

MATERIALS AND METHODS

RESULTS

DISCUSSION

REFERENCES

CHAPTER 78. STEROID-16 α-HYDROXYLASE IN RAT LIVER: BIOCHEMICAL AND BIOLOGICAL PROPERTIES

INTRODUCTION

MATERIALS AND METHODS

RESULTS

DISCUSSION

REFERENCES

CHAPTER 79. CORRELATION BETWEEN DRUG, LIPID AND CARBOHYDRATE METABOLISM IN THE RAT AFTER CHRONIC BETA- ADRENORECEPTOR ANTAGONIST TREATMENT

ABSTRACT

INTRODUCTION

MATERIAL AND METHODS

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 80. CONVERSION OF TRICHLOROETHYLENE TO CARBON MONOXIDE BY MICROSOMAL CYTOCHROME P450

ABSTRACT

INTRODUCTION

RESULTS

DISCUSSION

ACKNOWLEDGMENT

REFERENCES

CHAPTER 81. STEREOSELECTIVE IN VITRO AROMATIC OXYGENATION OF CHIRAL1.4-BENZODIAZEPIN-2-ONES

REFERENCES

CHAPTER 82. EFFECTS OF DISEASE STATES ON DRUG DISPOSITION IN MAN

INTRODUCTION

REFERENCES

ACKNOWLEDGMENT

CHAPTER 83. ISOLATION OF RAT LIVER EPOXIDE HYDRATASE: PROPERTIES AND SUBSTRATE SPECIFICITY OF THE PURE ENZYME

ABSTRACT

INTRODUCTION

MATERIALS AND METHODS

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 84. REDUCTION OF A TERTIARY AMINE N-OXIDE AND AN ARENE OXIDE IN RELATION TO THE REDUCTION RATE OF CYTOCHROME P-450 IN RAT LIVER MICROSOMES

ABSTRACT

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

REFERENCES

CHAPTER 85. MICROSOMAL OXIDATION OF ISOPROTERENOL AND IRREVERSIBLE PROTEIN BINDING OF METABOLITES

ABSTRACT

INTRODUCTION

METHODS

RESULTS

DISCUSSION

REFERENCES

CHAPTER 86. BENZO (α) PYRENE METABOLISM BY MICROSOMES AND ISOLATED EPITHELIAL CELLS FROM RAT SMALL INTESTINE

METHODS

RESULTS AND COMMENTS

ACKNOWLEDGEMENT

REFERENCES

CHAPTER 87. CHARACTERIZATION OF THE DRUG MONOOXYGENASE SYSTEM IN MOUSE SMALL INTESTINE

ABSTRACT

INTRODUCTION

MATERIALS AND METHODS

RESULTS AND DISCUSSION

ACKNOWLEDGEMENT

REFERENCES

CHAPTER 88. FORMATION OF ALKYLATION AND CARBAMYLATION INTERMEDIATES AND CYTOCHROME P-450 CATALYZED MONOOXYGENATION OF THE 2-CHLOROETHYLNITROSOUREAS CCNU AND METHYL CCNU

ABSTRACT

INTRODUCTION

METHODS AND MATERIALS

RESULTS

DISCUSSION

REFERENCES

CHAPTER 89. PROPOSED MECHANISM FOR THE REDUCTIVE GLYCOSIDIC CLEAVAGE OF DAUNOMYCIN (NSC 82151) AND ADRIAMYCIN (NSC 123127)

INTRODUCTION

METHODS

RESULTS

REFERENCES

CHAPTER 90. COVALENT BINDING OF STYRENE OXIDE TO RAT LIVER MACROMOLECULES IN VIVO AND IN VITRO

ABSTRACT

INTRODUCTION

EXPERIMENTAL

RESULTS AND DISCUSSION

ACKNOWLEDGEMENTS

REFERENCES

PART III: OUTLOOK

CHAPTER 91. THE REGULATION OF HUMAN DRUG METABOLISM BY NUTRITIONAL FACTORS

ACKNOWLEDGEMENT

REFERENCES

CHAPTER 92. THE BAY-REGION THEORY:A QUANTUM MECHANICAL APPROACHTO AROMATIC HYDROCARBON-INDUCED CARCINOGENICITY

ACKNOWLEDGEMENT

REFERENCES

CHAPTER 93. THE ACTIVATION AND INDUCTION OF BIPHENYL HYDROXYLATION AND CHEMICAL CARCINOGENESIS

REFERENCES

CHAPTER 94. INTEGRATED ELECTRON TRANSFER:IRON STATES AND REGULATION

REFERENCES

CHAPTER 95. PURIFICATION OF LIVER MICROSOMAL CYTOCHROME P-450:HOPES AND PROMISES

Acknowledgment

References

CHAPTER 96. ACTIVE OXYGEN– FACT OR FANCY

INTRODUCTION

SUMMARY

References

INDEX