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Volume contents, author index and subject index to volume 34
PHARMACOLOGY & THERAPEUTICS Volume 34 Executive Editors
W. C. Bowman, A. M. Breckenridge
PERGAMON
and A. C. Sartorelli
PRESS
OXFORD . NEW YORK . BEIJING . FRANKFURT SzhO PAUL0 . SYDNEY . TOKYO . TORONTO
PHARMACOLOGY &THERAPEUTICS Chemotherapy, Toxicology and Metabolic Inhibitors Executive Editor: A. C. Sartorelli Yale University School of Medicine, New Haven, Connecticut 06510, USA
Associate
Editor:
Barbara
Department
Z. Renkin,
qf Pharmacology,
333 Cedar
Street,
Ph.D.
General and Systematic Pharmacology Executive Editor: W. C. Bowman University of Strathclyde, Department of Physiology 204 George Street, Glasgow Gl lXW, Scotland
& Pharmacology,
Royal
College,
Clinical Pharmacology and Therapeutics Executive Editor: A. M. Breckenridge University of Liverpool, Department Liverpool L69 3BX, England
of Pharmacology
& Therapeutics,
P.O.
Box
147,
Library Annual Subscription Rates-published in 4 volumes per annum of 3 issues each. Annual Subscription, 1989, DM 2150.00 including postage and insurance, 2 years, 1989/90, DM 4085.00. Specially Reduced Rates IO Individuals: Any individual whose institution takes out a library subscription may purchase a second or additional subscription for personal use at a much reduced rate of DM 740.00 annually. Subscribers to the Journal may claim a 20% discount off Encyclopedia volumes. Prices are subject to change without notice. Subscription enquiries from customers in North America should be sent to Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523, USA, and for the remainder of the world to Pergamon Press plc, Headington Hill Hall. Oxford OX3 OBW, England. At the end of the year, the Subscriber
will receive, free, the annual
subject
index
It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. By submitting a manuscript, the authors agree that the copyright for their article is transferred to the publisher if and when the article is accepted for publication. However, assignment of copyright is not required from authors who work for organisations which do not permit such assignment. The copyright covers the exclusive rights to reproduce and distribute the article, including reprints, photographic reproduction, microform or any other reproduction of similar nature and translations. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, electrostatic, magnetic tape, mechanical photocopying recording or otherwise, without permission in writing from the copyright holder.
Photocopying Information for Users in the USA.
The Item-Fee Code for this publication indicates that authorization to photocopy items for internal or persona! use is granted by the copyright holder for libraries and other users registered with the Copyright Clearance Center (CCC) Transactional Reporting Service provided the stated fee for copying. beyond that permitted by Section 107 or 108 of the United States Copyright Law, is paid. The appropriate remittance of $0.50 per page is paid directly to the Copyright Clearance Center Inc., 27 Congress Street, Salem, MA 01970.
Permission for other Use. The copyright owner’s consent does not extend to copying for general distribution, for promotion, for creating new works. or for resale. Specific written permission must be obtained from the publisher for such copying. Microform Subscriptions and Back Issues Back issues of all previously published volumes Pergamon journals in microform can be obtained 48106, USA.
are available direct from Pergamon from UMI. 300 North Zeeb Road,
Publishing and Advertising Offices Pergamon Press plc Headington Hill Hall Oxford OX3 OBW England
Pergamon Press Inc. Maxwell House Fairview Park, Elmsford New York 10523. USA
Press. Back issues of Ann Arbor, Michigan
Volume 34,1987,
Numbers l-3
CONTENTS
Number 1 Metabolism of protein anticancer agents: V. Bocci Photoaffinity labeling of the calcitonin receptor: J. IV. Moseley, D. M. Findlay, J. J. Gorman and T. J. Martin Ethanol metabolism: D. W. Crabb, W. F. Bosron and T.-K. Li Psoralens and related compounds in the treatment of psoriasis: M. T. McEvoy and R. S. Stern Serum enzymes of drug metabolism: F. M. Williams Metabolism of hydrazine anti-cancer agents: D. J. Tweedie, J. M. Erikson and R. A. Prough Drug metabolism in pregnancy, infancy and childhood: E. Perucca
PAGE
1 51 59 75 99 111 129
Number 2 High performance liquid chromatographic separation of DNA adducts induced by cancer chemotherapeutic agents: D. B. Ludlum The formation, isolation and characterization of DNA adducts produced by anticancer platinum complexes: A. Eastman Properties and assay of mammalian 06-alkylguanine-DNA alkyltransferase: A. E. Pegg and M. E. Dolan Properties and biological consequences of alkylpyrimidine deoxyribonucleosides: F. C. Richardson, R. 0. Beauchamp, Jr and J. A. Swenberg Quantitative estimation of cisplatin-induced DNA interstrand cross-links and their repair in mammalian cells: relationship to toxicity: .I. J. Roberts and F. Friedlos Structure and expression of the complement genes: D. H. Perlmutter and H. R. Coiten Photoaffinity labeling of Escherichia coli ribosomes: B. S. Cooperman Nucleoid sedimentation analysis of DNA strand breaks induced in cells exposed to DNA intercalating agents: A4. R. Mattern, D. J. Kerrigan and Y. Pommier The use of monoclonal antibody affinity columns for assessing DNA damage and repair following exposure to aflatoxin B,: J. D. Groopman and T. W. Kensler Photoaffinity labeling of human plasmin and plasminogen: T. J. Ryan
145 155 167 181
215 247 271 303
321 335
Number 3 Experimental manipulations of eating: Advances in animal models for studying anorectic agents: J. E. Blundell and P. L. Thurlby Current view on the structure-function relationship of postsynaptic neurotoxins from snake venoms: T. Endo and N. Tamiya Ethanol and vitamin metabolism: C. H. Halsted and C. Heise
349 403 453
AUTHOR Beauchamp, R. 0. Jr Blundell, J. E. 349 Bocci, V. 1 Bosron, W. F. 59
Colten, H. R. 247 Cooperman, B. S. 271 Crabb, D. W. 59
Dolan,
M. E.
167
Eastman, A. 155 Endo, T. 403 Erikson, J. M. 11 I
Findlay, D. M. 51 Friedlos, F. 215
Gorman, J. J. 51 Groopman, J. D. 321
Halsted, C. H. Heise, C. 453
453
Kensler, T. W. Kerrigan, D. J.
321 303
181
INDEX
Li, T.-K. 59 Ludlum, D. B.
145
Martin, T. J. 51 Mattern, M. R. 303 McEvoy, M. T. 75 Moseley, J. M. 51
Pegg, A. E. 167 Perlmutter, D. H. 247 Perucca, E. 129 Pommier, Y. 303 Prough, R. A. 111
Richardson, F. C. 181 Roberts, J. J. 215 Ryan, T. J. 335
Stern, R. S. 75 Swenberg, J. A.
18 1
Tamiya, N. 403 Thurlby, P. L. 349 Tweedie, D. J. 111
Williams,
F. M.
99
SUBJECT INDEX
Acetylcholinesterase inhibitors, hydrolysis 106 Adverse drug reactions psoralens 8 I,82 PUVA 86-89 Affinity chromatogrpahy monoclonal antibody 326, 327 human urine 332 rat urine 329 Aflatoxin BI dietary antioxidant, model 327-29 DNA damage assessment 321-34 liver cancer 322 metabolic activation 323 monoclonal antibody preparation 324 -27 standards, HPLC 330 structures 322 Alcohol dehydrogenase 61 factors affecting 66-68 structure 62 Aldehyde dehydrogenases, ethanol metabolism 64, 65 06-Alkylguanine repair 167, 168 06-Alkylguanine-DNA alkyltransferase 167-75 activity 169 assays 173-75 distribution 168, 169 lesion repair 170-72 reduction 172, 173 specificity 170-72 Alkylpyrimidine deoxyribonucleosides accumulation 202 alkylation 183 biological correlates 205-207 chemicals generating 185-88 detection methods 189, 190 diethylnitrosamine 205, 206 formation, factors influencing 184-89 misincorporation 194-96 mutagenesis 191-96 properties 182-91 quantitation 190, 191 removal 204,205 renair 196-202 stability 183, 184 Amino acids amino-acid-albumin polymer IO antitumor protein degradation 7-10 clearance times 9 AMSA DNA breaks 315-17 structures 303 Angelicins metabolism 81 Anorectic agents 349-57 properties 350-54 Anorexia, spontaneous 382 Antibiotics, E. co/i ribosome effects 289-93 Antitumor agents see also protein Aryltransferases, drug metabolism 101 Aspirin, serum hydrolases 102, 103
Bungarotoxin,
conformation
411,412
Calcitonin amino acid sequence 51 iodination 54 photoactive 52, 53 synthesis, salmon 52, 53 Cancer chemotherapy, DNA adducts 145-52, 155-64 Carboplatin half-life 226 Carboxylesterases, drug metabolism 101 Cardiotoxins 408,408 Catalase 64 Chalones 16, 17 Children, drug metabolism 137-40 Chloramphenicol and ribosome effects 290, 291 Cholinesterases, drug metabolism 99-101 Cisplatin cross-linking alkaline elution 236-38 determination 218-38 formation and loss 230-32, 234, 235 method comparison 238-41 method sensitivities 240, 241 renaturable fraction 232-35 simulated results 229 stability 223-27 X-irradiated sedimentation 227-32 cytotoxicity 215-17 and cross-linking 241-43 DNA reactions 217, 218 half-life 226 hybrid DNA 218-21 CNS lesions and eating behavior 370-73 Cobratoxin conformation 411,415,417,418 Combination therapy, PUVA 89-91 Complement activation pathway 249,250 Cl 260 C2 252-55 C3 258-60 C4 255-58 C5 258-60 characteristics 247 deficiencies 256 factor B, scheme 252-55 factor D 260 membrane attack complex 260, 261 regulatory proteins 261-63 scheme 248 Complement gene localization 25 1 proteins 255 structure and expression 251, 252 Cytotoxicity, cisplatin and cross-linking 241-43 Cytotoxins see a/so protein, antitumor DNA glutathione platination
cross-linking 169
162
vi
SUBJECT
DNA adducts half-lives in vivo 200, 201 HPLC 145-52 interstrand cross-links 157-61 characterization 161, 162 nucleoside release 146, 147 platinum coordination complex 155-64 cells 162, 163 ultraviolet spectra 150 DNA damage assessment 321-34 DNA intercalating agents DNA linking number 314-18 strand break analysis 303-18 DNA strand breaks alkaline elution 304 protein concealed 304-306 DNA supercoiling 310 DNA topoisomerases 304, 306 nucleoid sedimentation analysis 311-18 Drugs and food intake 349-57 see also anorectic agents ambivalent effects 357 enhancement 354-57 suppressing 350-54 Drug metabolism serum enzymes 99-107 serum hydrolysis 102-106
Eating, experimental manipulation Erabutoxin conformation 410,411,415 electrostatic potential 435 Ethanol metabolism 59-70 absorption 59 and alcohol consumption 68 elimination curves 59-61 genetics 69 enzymes 61-65 and folate 453 excretion 455 hepatobiliary metabolism 454 intestinal effects 453, 454 microsomal oxidation 63,64 pyridoxine 455-57 rate, factors affecting 65 thiamine metabolism 457-59 vitamin A metabolism 459-61 and zinc 461
349-88
Feeding arousal 368,369 behavior 358, 359 micro-structural analysis 361, 362 structure 369 castration effects 374, 375 chemical adjustment 376-78 CNS lesions 370-73 continuous monitoring 366 deprivation-induced 359, 360 environmental influences 383-88 genetic adjustments 378-81 hypophysectomy 375 intestinal surgery 375 novelty 366-68 nutrient self-selection 364-66 physiological changes and 381-83 profiles 362-64 temperature 383 Fetoplacental unit, drug metabolism 129, 130
INDEX Fibrinolytic system 335, 336 Folate and ethanol 453-55 Food intake diet adjustment 364 pharmacological suppression Furrocoumarins 75
360, 361
High-performance liquid chromatography (HPLC) chemotherapy, DNA adducts 145-52 quantitative 151, 152 DNA adduct separation 147-5 1 nucleoside separation 147 platinum coordinated DNA adducts 157-59 Hydrazine anticancer agents 11 l-24 animal studies 111,112 enzymology 120-22 factors affecting 123, 124 metabolic activation pathways 122, 123 metabolism in vitro 118 invivo 117 mutagenicity 114, 115 toxicity 113, 114
Immunoglobulins, half-lives 11 Immunotoxins IO-14 behavior 14 extravasation 13 Infants, drug metabolism 137-40 Interferons cell effects 21 characteristics 17 half-lives 18, 19 inactivation 21 organ effects 21-23 pharmacology 20 Interleukins 24, 25
Lysine-binding sites, plasmin and plasminogen 337-40 role 345
Monoclonal antibodies affinity columns and DNA damage half-lives IO-14 MOPP cancer treatment I 13
321-34
Neocarzinostatin (NCS) properties 15, 16 Neonates, drug metabolism 134-39 inducibility 137 Neurotoxins, postsynaptic amino acid sequences 406, 407 binding conformational change 433,434 conformation 41 l-22 crystal and solution 414, 415 C-terminal tail 429, 430 definition 403 dynamic structure 418-20 fluorescent-labeled 437, 438 folding 407 functional residues 427-29 hydrophobic core 421,422 invariant residues 408-10 primary structure 404 receptor interaction 437-39 receptor reactions 422-40
SUBJECT spin-labeled 437 stopped-flow fluorescence 438,439 structure-function 403-41 structure maintenance 420-22 Nucleoid sedimentation analysis 303-18 DNA compactness 309 DNA topology 307,308 information 308 topoisomerase hypothesis 3 1 l-l 8 validity 3 11
Photoaffinity labeling calcitonin receptor 51-58 plasmin 335-46 properties affected 341-43 technique 341 plasminogen 343-45 procedure 55-58 ribosomes, .E. co/i 271-98 functional centers 293-97 particles 279-8 1 protein factors 287-89 proteins labeled 275-77 RNA regions labeled 277-82 Plasminogen/plasmin lysine-binding sites 337-40 role 345 photoaffinity labeling 340-45 Platinum coordination complexes DNA adducts 155-64 characterization 156 structures 155 Pregnancy adrenergic blockers 133, 134 antiepileptics 133 drug disposition 130-34 drug metabolism 129-34 plasma clearance 130 Procarbazine activation pathway 119 chemistry 115-17 degradation pathway 116 metabolism 11 l-24 structure 112 Prodrugs, serum hydrolysis 105, 106 Proteins, antitumor l-32 see also individual compounds, classes amino acids degrading 7-10 antigenicity 28 capillary permeability 2 catabolism 4 cytotoxins 4-7 distribution 1, 2, 3 isolation 28 metabolic sites 5 toxicity 30 tumor uptake 29, 30 Protein biosynthesis, reaction sequence on ribosomes 271-73 Psoralens metabolism 81
INDEX
vii
pharmacokinetics 79-81 in psoriasis 75-91 Psoriasis photoimmunology 77-79 psoralen treatment 75-91 PUVA acute responses 82 adverse effects 86-89 carcinogenicity 86, 87 combination therapy 89-91 immunologic effects 87 mechanism of action 76, 77 pigmented tissues 87, 88 psoriasis treatment 82-86 maintenance 85, 86 results 84 skin types 85
Receptor, acetylcholine binding region 430-33 mimic structure 431 neurotoxin binding 423-27 species differences 440 structure 422 synthesis 426 Receptor, calcitonin calcitonin binding 53 photoaffinity labeling 51-58 Receptors, complement C3 263,264 Ribosomes anticodon loop 283,284 functional centers 293-97 functional sites 274 peptidyl transferase 294-96 photoaffinity labeling in E. coli 271-98 protein topography 273 mRNA binding center 296, 297 structural studies 271-75 mRNA, photoaffinity labeling 286, 287 tRNA photoaffinity labeling 282-86 structure 278
Snake venoms Suxamethonium,
403-41 see also neurotoxins serum hydrolysis 104
Thiamine and ethanol metabolism 457-59 Thymic hormones 25,26 Transfer factor metabolism 26, 27 Tuftsin metabolism 27 Tumor necrosis factor (TNFa) 5, 6
Vitamin Vitamin Vitamin
A, ethanol effects 459-61 86 and ethanol 455-57 metabolism and ethanol 453-62
Zinc and ethanol
461,462
W. C. Bowman, A. M. Breckenridge
PERGAMON
and A. C. Sartorelli
PRESS
OXFORD . NEW YORK . BEIJING . FRANKFURT SzhO PAUL0 . SYDNEY . TOKYO . TORONTO
PHARMACOLOGY &THERAPEUTICS Chemotherapy, Toxicology and Metabolic Inhibitors Executive Editor: A. C. Sartorelli Yale University School of Medicine, New Haven, Connecticut 06510, USA
Associate
Editor:
Barbara
Department
Z. Renkin,
qf Pharmacology,
333 Cedar
Street,
Ph.D.
General and Systematic Pharmacology Executive Editor: W. C. Bowman University of Strathclyde, Department of Physiology 204 George Street, Glasgow Gl lXW, Scotland
& Pharmacology,
Royal
College,
Clinical Pharmacology and Therapeutics Executive Editor: A. M. Breckenridge University of Liverpool, Department Liverpool L69 3BX, England
of Pharmacology
& Therapeutics,
P.O.
Box
147,
Library Annual Subscription Rates-published in 4 volumes per annum of 3 issues each. Annual Subscription, 1989, DM 2150.00 including postage and insurance, 2 years, 1989/90, DM 4085.00. Specially Reduced Rates IO Individuals: Any individual whose institution takes out a library subscription may purchase a second or additional subscription for personal use at a much reduced rate of DM 740.00 annually. Subscribers to the Journal may claim a 20% discount off Encyclopedia volumes. Prices are subject to change without notice. Subscription enquiries from customers in North America should be sent to Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523, USA, and for the remainder of the world to Pergamon Press plc, Headington Hill Hall. Oxford OX3 OBW, England. At the end of the year, the Subscriber
will receive, free, the annual
subject
index
It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. By submitting a manuscript, the authors agree that the copyright for their article is transferred to the publisher if and when the article is accepted for publication. However, assignment of copyright is not required from authors who work for organisations which do not permit such assignment. The copyright covers the exclusive rights to reproduce and distribute the article, including reprints, photographic reproduction, microform or any other reproduction of similar nature and translations. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, electrostatic, magnetic tape, mechanical photocopying recording or otherwise, without permission in writing from the copyright holder.
Photocopying Information for Users in the USA.
The Item-Fee Code for this publication indicates that authorization to photocopy items for internal or persona! use is granted by the copyright holder for libraries and other users registered with the Copyright Clearance Center (CCC) Transactional Reporting Service provided the stated fee for copying. beyond that permitted by Section 107 or 108 of the United States Copyright Law, is paid. The appropriate remittance of $0.50 per page is paid directly to the Copyright Clearance Center Inc., 27 Congress Street, Salem, MA 01970.
Permission for other Use. The copyright owner’s consent does not extend to copying for general distribution, for promotion, for creating new works. or for resale. Specific written permission must be obtained from the publisher for such copying. Microform Subscriptions and Back Issues Back issues of all previously published volumes Pergamon journals in microform can be obtained 48106, USA.
are available direct from Pergamon from UMI. 300 North Zeeb Road,
Publishing and Advertising Offices Pergamon Press plc Headington Hill Hall Oxford OX3 OBW England
Pergamon Press Inc. Maxwell House Fairview Park, Elmsford New York 10523. USA
Press. Back issues of Ann Arbor, Michigan
Volume 34,1987,
Numbers l-3
CONTENTS
Number 1 Metabolism of protein anticancer agents: V. Bocci Photoaffinity labeling of the calcitonin receptor: J. IV. Moseley, D. M. Findlay, J. J. Gorman and T. J. Martin Ethanol metabolism: D. W. Crabb, W. F. Bosron and T.-K. Li Psoralens and related compounds in the treatment of psoriasis: M. T. McEvoy and R. S. Stern Serum enzymes of drug metabolism: F. M. Williams Metabolism of hydrazine anti-cancer agents: D. J. Tweedie, J. M. Erikson and R. A. Prough Drug metabolism in pregnancy, infancy and childhood: E. Perucca
PAGE
1 51 59 75 99 111 129
Number 2 High performance liquid chromatographic separation of DNA adducts induced by cancer chemotherapeutic agents: D. B. Ludlum The formation, isolation and characterization of DNA adducts produced by anticancer platinum complexes: A. Eastman Properties and assay of mammalian 06-alkylguanine-DNA alkyltransferase: A. E. Pegg and M. E. Dolan Properties and biological consequences of alkylpyrimidine deoxyribonucleosides: F. C. Richardson, R. 0. Beauchamp, Jr and J. A. Swenberg Quantitative estimation of cisplatin-induced DNA interstrand cross-links and their repair in mammalian cells: relationship to toxicity: .I. J. Roberts and F. Friedlos Structure and expression of the complement genes: D. H. Perlmutter and H. R. Coiten Photoaffinity labeling of Escherichia coli ribosomes: B. S. Cooperman Nucleoid sedimentation analysis of DNA strand breaks induced in cells exposed to DNA intercalating agents: A4. R. Mattern, D. J. Kerrigan and Y. Pommier The use of monoclonal antibody affinity columns for assessing DNA damage and repair following exposure to aflatoxin B,: J. D. Groopman and T. W. Kensler Photoaffinity labeling of human plasmin and plasminogen: T. J. Ryan
145 155 167 181
215 247 271 303
321 335
Number 3 Experimental manipulations of eating: Advances in animal models for studying anorectic agents: J. E. Blundell and P. L. Thurlby Current view on the structure-function relationship of postsynaptic neurotoxins from snake venoms: T. Endo and N. Tamiya Ethanol and vitamin metabolism: C. H. Halsted and C. Heise
349 403 453
AUTHOR Beauchamp, R. 0. Jr Blundell, J. E. 349 Bocci, V. 1 Bosron, W. F. 59
Colten, H. R. 247 Cooperman, B. S. 271 Crabb, D. W. 59
Dolan,
M. E.
167
Eastman, A. 155 Endo, T. 403 Erikson, J. M. 11 I
Findlay, D. M. 51 Friedlos, F. 215
Gorman, J. J. 51 Groopman, J. D. 321
Halsted, C. H. Heise, C. 453
453
Kensler, T. W. Kerrigan, D. J.
321 303
181
INDEX
Li, T.-K. 59 Ludlum, D. B.
145
Martin, T. J. 51 Mattern, M. R. 303 McEvoy, M. T. 75 Moseley, J. M. 51
Pegg, A. E. 167 Perlmutter, D. H. 247 Perucca, E. 129 Pommier, Y. 303 Prough, R. A. 111
Richardson, F. C. 181 Roberts, J. J. 215 Ryan, T. J. 335
Stern, R. S. 75 Swenberg, J. A.
18 1
Tamiya, N. 403 Thurlby, P. L. 349 Tweedie, D. J. 111
Williams,
F. M.
99
SUBJECT INDEX
Acetylcholinesterase inhibitors, hydrolysis 106 Adverse drug reactions psoralens 8 I,82 PUVA 86-89 Affinity chromatogrpahy monoclonal antibody 326, 327 human urine 332 rat urine 329 Aflatoxin BI dietary antioxidant, model 327-29 DNA damage assessment 321-34 liver cancer 322 metabolic activation 323 monoclonal antibody preparation 324 -27 standards, HPLC 330 structures 322 Alcohol dehydrogenase 61 factors affecting 66-68 structure 62 Aldehyde dehydrogenases, ethanol metabolism 64, 65 06-Alkylguanine repair 167, 168 06-Alkylguanine-DNA alkyltransferase 167-75 activity 169 assays 173-75 distribution 168, 169 lesion repair 170-72 reduction 172, 173 specificity 170-72 Alkylpyrimidine deoxyribonucleosides accumulation 202 alkylation 183 biological correlates 205-207 chemicals generating 185-88 detection methods 189, 190 diethylnitrosamine 205, 206 formation, factors influencing 184-89 misincorporation 194-96 mutagenesis 191-96 properties 182-91 quantitation 190, 191 removal 204,205 renair 196-202 stability 183, 184 Amino acids amino-acid-albumin polymer IO antitumor protein degradation 7-10 clearance times 9 AMSA DNA breaks 315-17 structures 303 Angelicins metabolism 81 Anorectic agents 349-57 properties 350-54 Anorexia, spontaneous 382 Antibiotics, E. co/i ribosome effects 289-93 Antitumor agents see also protein Aryltransferases, drug metabolism 101 Aspirin, serum hydrolases 102, 103
Bungarotoxin,
conformation
411,412
Calcitonin amino acid sequence 51 iodination 54 photoactive 52, 53 synthesis, salmon 52, 53 Cancer chemotherapy, DNA adducts 145-52, 155-64 Carboplatin half-life 226 Carboxylesterases, drug metabolism 101 Cardiotoxins 408,408 Catalase 64 Chalones 16, 17 Children, drug metabolism 137-40 Chloramphenicol and ribosome effects 290, 291 Cholinesterases, drug metabolism 99-101 Cisplatin cross-linking alkaline elution 236-38 determination 218-38 formation and loss 230-32, 234, 235 method comparison 238-41 method sensitivities 240, 241 renaturable fraction 232-35 simulated results 229 stability 223-27 X-irradiated sedimentation 227-32 cytotoxicity 215-17 and cross-linking 241-43 DNA reactions 217, 218 half-life 226 hybrid DNA 218-21 CNS lesions and eating behavior 370-73 Cobratoxin conformation 411,415,417,418 Combination therapy, PUVA 89-91 Complement activation pathway 249,250 Cl 260 C2 252-55 C3 258-60 C4 255-58 C5 258-60 characteristics 247 deficiencies 256 factor B, scheme 252-55 factor D 260 membrane attack complex 260, 261 regulatory proteins 261-63 scheme 248 Complement gene localization 25 1 proteins 255 structure and expression 251, 252 Cytotoxicity, cisplatin and cross-linking 241-43 Cytotoxins see a/so protein, antitumor DNA glutathione platination
cross-linking 169
162
vi
SUBJECT
DNA adducts half-lives in vivo 200, 201 HPLC 145-52 interstrand cross-links 157-61 characterization 161, 162 nucleoside release 146, 147 platinum coordination complex 155-64 cells 162, 163 ultraviolet spectra 150 DNA damage assessment 321-34 DNA intercalating agents DNA linking number 314-18 strand break analysis 303-18 DNA strand breaks alkaline elution 304 protein concealed 304-306 DNA supercoiling 310 DNA topoisomerases 304, 306 nucleoid sedimentation analysis 311-18 Drugs and food intake 349-57 see also anorectic agents ambivalent effects 357 enhancement 354-57 suppressing 350-54 Drug metabolism serum enzymes 99-107 serum hydrolysis 102-106
Eating, experimental manipulation Erabutoxin conformation 410,411,415 electrostatic potential 435 Ethanol metabolism 59-70 absorption 59 and alcohol consumption 68 elimination curves 59-61 genetics 69 enzymes 61-65 and folate 453 excretion 455 hepatobiliary metabolism 454 intestinal effects 453, 454 microsomal oxidation 63,64 pyridoxine 455-57 rate, factors affecting 65 thiamine metabolism 457-59 vitamin A metabolism 459-61 and zinc 461
349-88
Feeding arousal 368,369 behavior 358, 359 micro-structural analysis 361, 362 structure 369 castration effects 374, 375 chemical adjustment 376-78 CNS lesions 370-73 continuous monitoring 366 deprivation-induced 359, 360 environmental influences 383-88 genetic adjustments 378-81 hypophysectomy 375 intestinal surgery 375 novelty 366-68 nutrient self-selection 364-66 physiological changes and 381-83 profiles 362-64 temperature 383 Fetoplacental unit, drug metabolism 129, 130
INDEX Fibrinolytic system 335, 336 Folate and ethanol 453-55 Food intake diet adjustment 364 pharmacological suppression Furrocoumarins 75
360, 361
High-performance liquid chromatography (HPLC) chemotherapy, DNA adducts 145-52 quantitative 151, 152 DNA adduct separation 147-5 1 nucleoside separation 147 platinum coordinated DNA adducts 157-59 Hydrazine anticancer agents 11 l-24 animal studies 111,112 enzymology 120-22 factors affecting 123, 124 metabolic activation pathways 122, 123 metabolism in vitro 118 invivo 117 mutagenicity 114, 115 toxicity 113, 114
Immunoglobulins, half-lives 11 Immunotoxins IO-14 behavior 14 extravasation 13 Infants, drug metabolism 137-40 Interferons cell effects 21 characteristics 17 half-lives 18, 19 inactivation 21 organ effects 21-23 pharmacology 20 Interleukins 24, 25
Lysine-binding sites, plasmin and plasminogen 337-40 role 345
Monoclonal antibodies affinity columns and DNA damage half-lives IO-14 MOPP cancer treatment I 13
321-34
Neocarzinostatin (NCS) properties 15, 16 Neonates, drug metabolism 134-39 inducibility 137 Neurotoxins, postsynaptic amino acid sequences 406, 407 binding conformational change 433,434 conformation 41 l-22 crystal and solution 414, 415 C-terminal tail 429, 430 definition 403 dynamic structure 418-20 fluorescent-labeled 437, 438 folding 407 functional residues 427-29 hydrophobic core 421,422 invariant residues 408-10 primary structure 404 receptor interaction 437-39 receptor reactions 422-40
SUBJECT spin-labeled 437 stopped-flow fluorescence 438,439 structure-function 403-41 structure maintenance 420-22 Nucleoid sedimentation analysis 303-18 DNA compactness 309 DNA topology 307,308 information 308 topoisomerase hypothesis 3 1 l-l 8 validity 3 11
Photoaffinity labeling calcitonin receptor 51-58 plasmin 335-46 properties affected 341-43 technique 341 plasminogen 343-45 procedure 55-58 ribosomes, .E. co/i 271-98 functional centers 293-97 particles 279-8 1 protein factors 287-89 proteins labeled 275-77 RNA regions labeled 277-82 Plasminogen/plasmin lysine-binding sites 337-40 role 345 photoaffinity labeling 340-45 Platinum coordination complexes DNA adducts 155-64 characterization 156 structures 155 Pregnancy adrenergic blockers 133, 134 antiepileptics 133 drug disposition 130-34 drug metabolism 129-34 plasma clearance 130 Procarbazine activation pathway 119 chemistry 115-17 degradation pathway 116 metabolism 11 l-24 structure 112 Prodrugs, serum hydrolysis 105, 106 Proteins, antitumor l-32 see also individual compounds, classes amino acids degrading 7-10 antigenicity 28 capillary permeability 2 catabolism 4 cytotoxins 4-7 distribution 1, 2, 3 isolation 28 metabolic sites 5 toxicity 30 tumor uptake 29, 30 Protein biosynthesis, reaction sequence on ribosomes 271-73 Psoralens metabolism 81
INDEX
vii
pharmacokinetics 79-81 in psoriasis 75-91 Psoriasis photoimmunology 77-79 psoralen treatment 75-91 PUVA acute responses 82 adverse effects 86-89 carcinogenicity 86, 87 combination therapy 89-91 immunologic effects 87 mechanism of action 76, 77 pigmented tissues 87, 88 psoriasis treatment 82-86 maintenance 85, 86 results 84 skin types 85
Receptor, acetylcholine binding region 430-33 mimic structure 431 neurotoxin binding 423-27 species differences 440 structure 422 synthesis 426 Receptor, calcitonin calcitonin binding 53 photoaffinity labeling 51-58 Receptors, complement C3 263,264 Ribosomes anticodon loop 283,284 functional centers 293-97 functional sites 274 peptidyl transferase 294-96 photoaffinity labeling in E. coli 271-98 protein topography 273 mRNA binding center 296, 297 structural studies 271-75 mRNA, photoaffinity labeling 286, 287 tRNA photoaffinity labeling 282-86 structure 278
Snake venoms Suxamethonium,
403-41 see also neurotoxins serum hydrolysis 104
Thiamine and ethanol metabolism 457-59 Thymic hormones 25,26 Transfer factor metabolism 26, 27 Tuftsin metabolism 27 Tumor necrosis factor (TNFa) 5, 6
Vitamin Vitamin Vitamin
A, ethanol effects 459-61 86 and ethanol 455-57 metabolism and ethanol 453-62
Zinc and ethanol
461,462