Peroxisomes: biology and importance in toxicology and medicine

555 Pages·1993·30.585 MB·English

by  Gibson, G. Gordon, Lake, Brian

Peroxisomes: Biology and Importance in
Toxicology and Medicine

Peroxisomes:
Biology and Importance in
Toxicology and Medicine
Edited by
Gordon Gibson
and
Brian Lake
Taylor & Francis
London Washington, DC
1993
UK Taylor & Francis Ltd, 4 John St., London WC1N 2ET
USA Taylor & Francis Inc., 1900 Frost Rd., Suite 101, Bristol, PA
19007
© Taylor & Francis Ltd. 1993
All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, or transmitted, in any
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British Library Cataloguing in Publication Data
are available on request from the British Library
ISBN 07484-0053-2
Library of Congress Cataloging-in-Publication Data
are available on request
Cover design by Amanda Barragry
Typeset in 10/12 Times by RGM/Witwell Assoc., Southport
Printed in Great Britain by Burgess Science Press, Basingstoke on
paper which has a specified pH value on final paper manufacture
of not less than 7.5 and is therefore 'acid free'.
Contents
Preface ix
Contributors xiii
1. Peroxisome biogenesis
G. M. Small 1
2. Metabolic role of mammalian peroxisomes
G. P. Mannaerts and P. P. Van Veldhoven 19
3. Peroxisomal disorders
R. J. A. Wanders, P. G. Barth, R. B. H. Schutgens and J. M. Tager 63
4. The molecular mechanism of peroxisome proliferator action
S. Green, I. Issemann and J. D. Tugwood 99
5. Peroxisome proliferators as cytochrome P450 inducers
G. G. Gibson, E. Chinje, O. Sabzevari, P. Kentish and
D. F. V. Lewis 119
6. Peroxisome proliferation — lipid metabolism and receptors
D. R. Bell and C. R. Elcombe 137
7. Molecular mechanisms involved in induction of peroxisomal
â-oxidation enzymes by hypolipidaemic agents
T. Osumi, J.-K. Wen, S. Taketani and T. Hashimoto 149
8. Molecular basis of gene regulation by peroxisome proliferators
N. Latruffe, M. Bugaut, P. Bournot, M. Bentejac, L. C. Ramirez
and M. Cherkaoui Malki 173
9. Molecular evolution of the urate oxidase encoding gene and its
functional significance
A. V. Yeldandi and V. Yeldandi 205
í
vi Contents
10. Possible role of CoASH esters on xenobiotic-induced peroxisomal
proliferation and non-genotoxic carcinogenesis
M. Bronfman 217
11. Modulation of peroxisomal biogenesis and lipid metabolising
enzymes by dietary factors
T. Flatmark and Å. N. Christiansen 247
12. Proliferation of peroxisomes and mitochondria and modulation of
lipid metabolizing enzymes by hypolipidaemic, non-â-oxidizable
fatty acids (3-thia fatty acids)
R. K. Berge, Ç. Kryvi, Í. Aarsaether, A. Aarsland and J. Skorve 277
13. Cultured hepatocytes: a useful in vitro system to investigate effects
induced by peroxisome proliferators and their species specificity
F. Bieri 299
14. Structure-activity relationships for chemically induced peroxisome
proliferation in mammalian liver
B. G. Lake and D. F. V. Lewis 313
15. Tetrazole substituted acetophenone peroxisome proliferators:
structure-activity relationships and effects on hepatic lipid
metabolism
P. J. Eacho, P. S. Foxworthy and D. K. Herron 343
16. Structural requirements for peroxisome proliferation by
phenoxyacetic and fatty acid analogues in primary cultures of rat
hepatocytes
D. R. Feller and U. Intrasuksri 373
17. Ultrastructural and biochemical aspects of peroxisome proliferation
and biogenesis in different mammalian species
H. D. Fahimi, E. Baumgart, Ê. Beier, J. Pill, F. Hartig and
A. Völkl 395
18. Toxicological studies in primates with three fibrates
M. J. Tucker and T. C. Orton 425
19. Structure-, enantiomer- and species-specific effects of fibrate
analogues on peroxisome proliferation and increased activity of
mitochondrial á-glycerophosphate dehydrogenase
B. R. Holloway and J. M. Thorp 449
Contents vu
20. Metabolism of di-(2-ethylhexyl)phthalate (DEHP) and
di-(2-ethylhexyl) adipate (DEHA) and their relationship to
peroxisome proliferation in different species
J. C. Lhuguenot and M. C. Cornu 465
21. Extrahepatic peroxisome proliferation and the extrahepatic effects
of peroxisome proliferators
R. H. Hinton and S. C. Price 487
22. Biological aspects of peroxisome proliferator-induced liver tumours
in the rat
M .S. Rao and J. K. Reddy 513
23. Genotoxicity studies of peroxisome proliferators
J. D. Budroe and G. M. Williams 525
24. Production of 8-hydroxydeoxyguanosine in rodent liver by the
administration of peroxisome proliferators
A. Takagi, K. Sai, T. Umemura, R. Hasegawa and Y. Kurokawa 569
25. Role of oxidative stress and enhanced cell replication in the
hepatocarcinogenicity of peroxisome proliferators
B. G. Lake 595
26. Hyperplastic responses to peroxisome proliferators
J. A. Styles 619
27. Hepatic changes associated with peroxisome proliferation
P. Grasso 639
28. Peroxisome proliferators as initiators and promoters of rodent
hepatocarcinogensis
J. A. Popp and R. C. Cattley 653
29. Are peroxisome proliferators tumour promoters in rat liver?
B. Grasl-Kraupp, W. Huber and R. Schulte-Hermann 667
30. Risk assessment of chemicals inducing peroxisome proliferation
W. T. Stott and N. C. Hawkins 695

Preface
Peroxisomes (or 'microbodies') are single membrane-limited cytoplasmic
organelles present in cells of animals, plants, fungi and protozoa. Studies by
De Duve and coworkers demonstrated that rat liver peroxisomes contain both
hydrogen peroxide generating oxidase enzymes and catalase. Later studies by
Lazarow and De Duve demonstrated that liver peroxisomes, like mitochon-
dria, contain a complete fatty acid â-oxidation cycle, whereas Hess and
coworkers first reported that clofibrate, a hypolipidaemic drug, could produce
hepatic peroxisome proliferation in the rat. Since these pioneering studies,
much effort has been devoted to elucidating the biochemical properties of these
organelles and their response to chemicals and other stimuli.
The various chapters contained in this volume cover all aspects of the
structure, function, regulation and response to chemicals of mammalian
peroxisomes. The biogenesis of peroxisomes in various species is considered by
Small, whereas the metabolic role of peroxisomes is described by Mannaerts
and Van Veldhoven. Peroxisome disorders in man are reviewed by Wanders
and coworkers.
Several chapters consider the mechanism of initiation of peroxisome
proliferation in hepatocytes together with aspects of the molecular biology of
peroxisomes and peroxisomal enzymes. Green and coworkers describe the
molecular mechanism of peroxisome proliferator action which appears to
involve one or more peroxisome proliferator-activated receptors. The mecha-
nism of initiation of peroxisome proliferation, together with the interaction
with lipid metabolism and receptors is covered by Bell and Elcombe. Rodent
liver peroxisome proliferators are known to induce cytochrome P450
isoenzymes in the CYP4A subfamily and the relationship of this phenomenon
to the mechanism of peroxisome proliferation is discussed by Gibson and
coworkers. The molecular basis of gene regulation by peroxisome proliferators
is also reviewed by Latruffe and coworkers, whereas Osumi and coworkers
describe in-depth studies on the regulatory sequence of the acyl-CoA oxidase
gene. The molecular evolution and functional significance of the urate oxidase
gene is reviewed by Yeldandi and Yeldandi. Many peroxisome proliferators or
their subsequent metabolites contain a free carboxyl group and hence may
form coenzyme A esters. The synthesis of such esters and their possible role in
peroxisome proliferation and the hepatic effects of peroxisome proliferation is
IX