Skip to main content
SpringerLink
Log in

Hepatic Peroxisome Proliferation: An Overview

  • Conference paper
The Target Organ and the Toxic Process

Part of the book series: Archives of Toxicology ((TOXICOLOGY,volume 12))

Abstract

Peroxisomes, single-membrane-bound cytoplasmic structures, are widely distributed in most animal and plant cells (Beevers 1979; Tolbert 1981). The identification and descriptions of the morphology of peroxisomes present in various eukaryotic cells are based on the assumption that they indeed represent subcellular organelles in which catalase is demonstrable by cytochemical or immunochemical procedures (Novikoff and Goldfischer 1968; Reddy et al. 1982; Bendayan and Reddy 1982; Usuda et al. 1988). Peroxisomes from the liver and kidney of rats and some other mammals have been shown to possess one or more H2O2-producing oxidases (Tolbert 1981; Usuda et al. 1986), but very little information exists regarding the presence of at least one such oxidase in organelles that have been identified as peroxisomes by catalase cytochemistry in other cell types. The availability of antibodies to some of the peroxismal oxidases (Osumi et al. 1984; Usuda et al. 1988) should make possible the immunocyto-chemical analysis of the distribution of these enzymes in various tissues. Recently it has been shown that urate oxidase is present only in the liver peroxisomes and not in other tissues of rat (Usuda et al. 1988).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Beevers H (1979) Microbodies in higher plants. Annu Rev Plant Physiol 30:159–194

    Article  CAS  Google Scholar 

  • Bendayan M, Reddy JK (1982) Immunocytochemical localization of catalase and heat-labile enoyl-CoA hydratase in the liver of normal and peroxisome proliferator-treated rats. Lab Invest 47:364–369

    PubMed  CAS  Google Scholar 

  • Cohen AJ, Grasso P (1981) Review of the hepatic response to hypolipidemic drugs in rodents and assessment of its toxicological significance to man. Food Cosmet Toxicol 19:585–605

    Article  PubMed  CAS  Google Scholar 

  • deDuve C (1973) Biochemical studies on the occurrence, biogenesis and life history of mammalian peroxisomes. J Histochem Cytochem 21:941–948

    Article  CAS  Google Scholar 

  • Furuta S, Hayashi H, Hijikata M, Miyazawa S, Takashi O, Hashimoto T (1986) Complete nucleotide sequence of cDNA and deduced amino acid sequence of rat liver catalase. Proc Natl Acad Sci USA 83:313–317

    Article  PubMed  CAS  Google Scholar 

  • Glauert HP, Reddy JK, Kennan YS, Sattler GL, Subbarao V, Pitot HC (1984) Effect of hypolipidemic peroxisome proliferators on unscheduled DNA synthesis in cultured hepato-cytes and on mutagenesis in Salmonella. Cancer Lett 26:147–156

    Article  Google Scholar 

  • Glauert HP, Beer D, Rao MS, Schwarz M, Xu Y, Goldsworthy TL, Coloma J, Pitot HC (1986) Induction of altered hepatic foci in rats by the administration of hypolipidemic peroxisome proliferators alone or following a single dose of diethyl-nitrosamine. Cancer Res 46:4601–4606

    PubMed  CAS  Google Scholar 

  • Greaves P, Irisarri E, Monro AM (1986) Hepatic foci of cellular and enzymatic alteration and nodules in rats treated with Clofibrate or diethylnitrosamine followed by phenobarbital: their rate of onset and their reversibility. J Natl Cancer Inst 76:475–484

    PubMed  CAS  Google Scholar 

  • Gupta RC, Goel SK, Earley K, Singh B, Reddy JK (1985) 32p-postlabeling analysis of peroxisome proliferator — DNA adduct formation in rat liver in vivo and hepatocytes in vitro. Carcinogenesis 6:933–936

    Article  PubMed  CAS  Google Scholar 

  • Hajra AK, Burke CL, Jones CL (1979) Subcellular localization of acyl coenzyme A: Dihy-droxyacetone phosphate acyltransferase in rat liver peroxisomes (microbodies). J Biol Chem 254:10896–10900

    PubMed  CAS  Google Scholar 

  • Hardwick JP, Song B-J, Huberban E, Gonzalez FJ (1987) Isolation complementray DNA sequence, and regulation of rat hepatic lauric acid ω-hydroxylase (cytochrome P-450 LAω). Identification of a new cytochrome P-450 gene family. J Biol Chem 262:801–810

    PubMed  CAS  Google Scholar 

  • Hashimoto T (1982) Individual peroxisomal beta-oxidation enzymes. Ann NY Acad Sci 386:5–12

    Article  PubMed  CAS  Google Scholar 

  • Hess R, Stäubli W, Reiss W (1965) Nature of the hepatomegalic effect produced by ethylchloro-phenoxyisobutyrate in the rat. Nature 208:856–858

    Article  PubMed  CAS  Google Scholar 

  • Hijikata M, Ishii N, Kagamiyama H, Osumi T, Hashimoto T (1987) Structural analysis of cDNA for rat peroxisomal 3-ketoacyl-CoA thiolase. J Biol Chem 262:8151–8158

    PubMed  CAS  Google Scholar 

  • Lalwani ND, Fahl WE, Reddy JK (1983) Detection of a nafenopin-binding protein in rat liver cytosol associated with the induction of peroxisome proliferation by hypolipidemic compounds. Biochem Biophys Res Commun 116:383–393

    Article  Google Scholar 

  • Lalwani ND, Alvares K, Reddy MK, Reddy MN, Parikh I, Reddy JK (1987) Peroxisome proliferator-binding protein: identification and partial characterization of nafenopin, clofibric acid-, and ciprofibrate-binding proteins from rat liver. Proc Natl Acad Sci USA 84:5242–5246

    Article  PubMed  CAS  Google Scholar 

  • Lazarow PB (1978) Rat liver peroxisomes catalyze the β-oxidation of fatty acids. J Biol Chem 253:1522–1528

    PubMed  CAS  Google Scholar 

  • Lazarow PB, DeDuve C (1976) A fatty acyl-CoA oxidizing system in rat liver peroxisomes; enhancement by Clofibrate, a hypolipidemic drug. Proc Natl Acad Sci USA 73:2043–2046

    Article  PubMed  CAS  Google Scholar 

  • Lazarow PB and Fujiki Y (1985) Biogenesis of peroxisomes. Annu Rev Cell Biol 1:489–530

    Article  PubMed  CAS  Google Scholar 

  • Lewis DFV, Lake BG, Gray TJB, Gangolli SD (1987) Structure activity requirements for induction of peroxisomal enzyme activities in primary rat hepatocyte cultures. Arch Toxicol Suppl 11:39–41

    PubMed  CAS  Google Scholar 

  • Moody DE, Reddy JK (1978) The hepatic effects of hypolipidemic drugs (Clofibrate, nafenopin, tibric acid and Wy-14,643) on hepatic peroxisomes and peroxisome-associated enzymes. Am J Pathol 90:435–446

    PubMed  CAS  Google Scholar 

  • Moody DE, Rao MS, Reddy JK (1977) Mitogenic effect in mouse liver induced by a hypolipidemic drug, nafenopin. Virchows Arch Abt B 23:291–296

    CAS  Google Scholar 

  • Moody DE, Loury DN, Hammock BD (1985) Epoxide metabolism in the liver of mice treated with Clofibrate (ethyl-α-(p-chlorophenoxyisobutyrate)), a peroxisome proliferator. Toxicol Appl Pharmacol 78:351–362

    Article  PubMed  CAS  Google Scholar 

  • Nebert DW, Gonzalez F (1987) P450 genes: Structure, evolution, and regulation. Annu Rev Biochem 56:945–993

    Article  PubMed  CAS  Google Scholar 

  • Nemali MR, Usuda N, Reddy MK, Oyasu K, Hashimoto T, Osumi T, Rao M, Reddy JK (1988) Comparison of constitutive and inducible levels of expression of peroxisomal β-oxidation and catalase genes in liver and extrahepatic tissues of rat. Cancer Res (in press)

    Google Scholar 

  • Novikoff AB, Goldfischer S (1968) Visualization of microbodies for light and electron microscopy. J Histochem Chytochem 16:507

    Google Scholar 

  • Osumi T, Ozasa H, Hashimoto T (1984) Molecular cloning of cDNA for rat acyl-CoA oxidase. J Biol Chem 259:2031–2034

    PubMed  CAS  Google Scholar 

  • Poland A, Knutson JC (1982) 2,3,7,8-Tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: Examination of the mechanism of toxicity. Annu Rev Pharmacol Toxicol 22:517–554

    Article  PubMed  CAS  Google Scholar 

  • Rao MS, Reddy JK (1987) Peroxisome proliferation and hepatocarcinogenesis. Carcinogenesis 8:631–636

    Article  PubMed  CAS  Google Scholar 

  • Rao MS, Lalwani ND, Scarpelli DG, Reddy JK (1982) The absence of γ-glutamyltranspeptidase activity in putative preneoplastic lesions and heptaocellular carcinomas induced in rats by the hypolipidemic peroxisome proliferator Wy-14,643. Carcinogenesis 3:1231–1233

    Article  PubMed  CAS  Google Scholar 

  • Rao MS, Lalwani ND, Reddy JK (1984) Sequential histologic study of rat liver during peroxisome proliferator [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14,643)-in-duced carcinogenesis. J Natl Cancer Inst 73:983–990

    PubMed  CAS  Google Scholar 

  • Rao MS, Nemali MR, Usuda N, Scarpelli DG, Makino T, Pitot HC, Reddy JK (1988) Lack of expression of glutathione-s-transferase P, γ-glutamyltranspeptidase and α-fetoprotein mRNAs in liver tumors induced by peroxisome proliferators. Cancer Res (in press)

    Google Scholar 

  • Rao MS, Tatematsu M; Subbarao V, Ito N, Reddy JK (1986) Analysis of peroxisome prolif-erator-induced preneoplastic and neoplastic lesions of rat liver for placental form of glutathione S-transferase and y-glutamyltranspeptidase. Cancer Res 46:5287–5290

    PubMed  CAS  Google Scholar 

  • Reddy JK, Krishnakantha TP (1975) Hepatic peroxisome proliferation: induction by two novel compounds structurally unrelated to Clofibrate. Science 190:787–789

    Article  PubMed  CAS  Google Scholar 

  • Reddy JK, Lalwani ND (1983) Carcinogenesis by hepatic peroxisome proliferators: evaluation of the risk of hypolipidemic drugs and industrial plasticizers to humans. Crit Rev Toxicol 12:1–58

    Article  PubMed  CAS  Google Scholar 

  • Reddy JK, Qureshi SA (1979) Tumorigenicity of the hypolipidemic peroxisome proliferator ethyl-α-p-chlorophenoxyisobutyrate (Clofibrate) in rats. Br J Cancer 40:476–482

    Article  PubMed  CAS  Google Scholar 

  • Reddy JK, Rao MS (1986) Peroxisome proliferators and cancer: mechanisms and implications. Trends Pharmacol Sci 7:438–443

    Article  CAS  Google Scholar 

  • Reddy JK, Rao MS (1987a) Xenobiotic-induced peroxisome proliferation: role of tissue specificity and species differences in response in the evaluation of the implications for human health. Arch Toxicol 10:43–53

    Article  CAS  Google Scholar 

  • Reddy JK, Rao MS (1987b) Peroxisome proliferation-related oxidative stress and hepatocar-cinogenesis. In Anticarcinogenesis and Radiation protection (Ceratti PA, Nygaard OF, Simic MG, Editors) Plenum Press, Wy pp 85–91

    Google Scholar 

  • Reddy JK, Rao MS, Moody DE (1976) Hepatocellular carcinomas in acatalasemic mice treated with nafenopin, a hypolipidemic peroxisome proliferator. Cancer Res 36:1211–1217

    PubMed  CAS  Google Scholar 

  • Reddy JK, Arzarnoff DL, Sirtori CR (1978) Hepatic peroxisome proliferation; induction by BR-931, a hypolipidemic analog of Wy-14,643. Arch Intl Pharmacodyn 234:4–14

    CAS  Google Scholar 

  • Reddy JK, Azarnoff DL, Hignite CE (1980) Hypolipidemic hepatic peroxisome proliferators form a novel class of chemical carcinogens. Nature 283:397–398

    Article  PubMed  CAS  Google Scholar 

  • Reddy JK, Warren JR, Reddy MK, Lalwani ND (1982) Hepatic and renal effects of peroxisome proliferators: biological implications. Ann NY Acad Sci 386:81–110

    Article  PubMed  CAS  Google Scholar 

  • Reddy JK, Lalwani ND, Qureshi SA, Reddy MK, Moehle CM (1984) Induction of hepatic peroxisome proliferation in non-rodent species, including primates. Am J Pathol 114:171–183

    PubMed  CAS  Google Scholar 

  • Reddy JK, Goel SK, Nemali MR, Carrino JJ, Laffler TG, Reddy MK, Sperbeck SJ, Osumi T, Hashimoto T, Lalwani ND, Rao MS (1986) Transcriptional regulation of peroxisomal fatty acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase in rat liver by peroxisome proliferators. Proc Natl Acad Sci (USA) 83:1747–1751

    Article  CAS  Google Scholar 

  • Reddy PG, Nemali MR, Usuda N, Rao MS, Reddy JK (1987) Cloning of cDNA for rat peroxisomal urate oxidase: Liver specific expression in the rat. J Cell Biol 105:157a

    Google Scholar 

  • Russo JJ, Black VH (1982) Hormone-dependent changes in peroxisomal enzyme activity in guinea pig adrenal. J Biol Chem 253:3883–3889

    Google Scholar 

  • Small GM, Hocking TJ, Sturdee AP, Burdett K, Connock M J (1981) Enhancement by dietary Clofibrate of peroxisomal palmityl-CoA oxidase in kidney and small intestine of albino mice and liver of genetically lean and obese mice. Life Sci 28:1875–1822

    Article  PubMed  CAS  Google Scholar 

  • Svoboda DJ; Azarnoff DL (1979) Tumors in male rats fed ethyl chlorophenoxyisobutyrate, a hypolipidemic drug. Cancer Res 39:3419–3428

    PubMed  CAS  Google Scholar 

  • Tamburini PD, Masson HA, Bains SK, Makowski RJ, Morris B, Gibson GG (1984) Multiple forms of hepatic cytochrome P-450 purification, characterization and comparison of a novel clofibrate-induced isozyme with other major forms of cytochrome P-450. Eur J Biochem 139:235–246

    Article  PubMed  CAS  Google Scholar 

  • Tolbert NE (1981) Metabolic pathways in peroxisomes and glyoxysomes. Annu Rev Biochem 50:133–157

    Article  PubMed  CAS  Google Scholar 

  • Tomaszewski KE, Agarwal DK, Melnick RL (1986) In vitro steady-state levels of hydrogen peroxide after exposure of male F344 rats and B6C3F1 mice to hepatic peroxisome proliferators. Carcinogenesis 7:1871–1876

    Article  PubMed  CAS  Google Scholar 

  • Usuda N, Yokota S, Hashimoto T, Nagata T (1986) Immunocytochemical localization of D-amino acid oxidase in the central clear matrix of rat kidney peroxisomes. J Histochem Cytochem 34:1709

    Article  PubMed  CAS  Google Scholar 

  • Usuda N, Reddy MK, Rao MS, Reddy JK (1988) Tissue specificity and species differences in the distribution of urate oxidase in peroxisomes. Lab Invest 58:100–111

    PubMed  CAS  Google Scholar 

  • Warren JR, Simmon VF, Reddy JK (1980) Properties of hypolipidemic peroxisome proliferators in the lymphocyte [3H]thymidine and Salmonella mutagenesis assays. Cancer Res 40:36–41

    PubMed  CAS  Google Scholar 

  • Wirth PJ; Rao MS, Evarts RP (1987) Coordinate polypeptide expression during hepatocarcino-genesis in male F-344 rats: Comparison of the Solt-Farber and Reddy models. Cancer Res 47:2839–2851

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, Illinois, 60611, USA

    J. K. Reddy, N. Usuda & M. S. Rao

Authors
  1. J. K. Reddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. Usuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. S. Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pharmacology and Therapeutics, Trinity College, University of Dublin, Dublin 2, Ireland

    Philip L. Chambers  & Claire M. Chambers  & 

  2. Institute de Biologie Moléculaire et Cellulaire du Centre National de la Recherche Scientifique and Faculté de Pharmacie, Université Louis Pasteur, 15, rue René Descartes, 67084, Strasbourg, France

    Guy Dirheimer

Rights and permissions

Reprints and permissions

Copyright information

© 1988 Springer-Verlag

About this paper

Cite this paper

Reddy, J.K., Usuda, N., Rao, M.S. (1988). Hepatic Peroxisome Proliferation: An Overview. In: Chambers, P.L., Chambers, C.M., Dirheimer, G. (eds) The Target Organ and the Toxic Process. Archives of Toxicology, vol 12. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73113-6_35

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-73113-6_35

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-18512-3

  • Online ISBN: 978-3-642-73113-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation