An overview of peroxisome proliferator-induced hepatocarcinogenesis. 1991

M S Rao, and J K Reddy
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611.

Peroxisome proliferators are hepatocarcinogens in rats and mice. Chronic administration of these compounds results in the development of altered areas and neoplastic nodules followed by hepatocellular carcinomas. All three types of hepatic lesions do not express gamma-glutamyltranspeptidase, glutathione 8-transferase-P, and alpha-fetoprotein and are resistant to iron accumulation after overload. The mechanism by which nongenotoxic peroxisome proliferators induce hepatic tumors is not well understood. It has been proposed that with continuous administration of peroxisome proliferators, liver cells are subjected to persistent oxidative stress resulting from marked proliferation of peroxisomes and a differential increase in the levels of H2O2 producing (20- to 30-fold) and degrading (2-fold) enzymes. Free oxygen radicals lead to DNA damage (both directly and through lipid peroxidation) and thus may cause initiation and promotion of the carcinogenic process.

UI MeSH Term Description Entries
D006984 Hypertrophy General increase in bulk of a part or organ due to CELL ENLARGEMENT and accumulation of FLUIDS AND SECRETIONS, not due to tumor formation, nor to an increase in the number of cells (HYPERPLASIA). Hypertrophies
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008114 Liver Neoplasms, Experimental Experimentally induced tumors of the LIVER. Hepatoma, Experimental,Hepatoma, Morris,Hepatoma, Novikoff,Experimental Hepatoma,Experimental Hepatomas,Experimental Liver Neoplasms,Hepatomas, Experimental,Neoplasms, Experimental Liver,Experimental Liver Neoplasm,Liver Neoplasm, Experimental,Morris Hepatoma,Novikoff Hepatoma
D008830 Microbodies Electron-dense cytoplasmic particles bounded by a single membrane, such as PEROXISOMES; GLYOXYSOMES; and glycosomes. Glycosomes,Glycosome,Microbody
D009255 Nafenopin A peroxisome proliferator that is used experimentally to promote liver tumors. It has been used as an antihyperlipoproteinemic agent. CH-13437,Melipan,Nafenoic Acid,SU-13,437,Acid, Nafenoic,CH 13437,CH13437,SU 13,437,SU13,437
D009363 Neoplasm Proteins Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm. Proteins, Neoplasm
D010084 Oxidation-Reduction A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). Redox,Oxidation Reduction
D010100 Oxygen An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration. Dioxygen,Oxygen-16,Oxygen 16
D010795 Phthalic Acids A group of compounds that has the general structure of a dicarboxylic acid-substituted benzene ring. The ortho-isomer is used in dye manufacture. (Dorland, 28th ed) Acids, Phthalic
D010968 Plasticizers Materials incorporated mechanically in plastics (usually PVC) to increase flexibility, workability or distensibility; due to the non-chemical inclusion, plasticizers leach out from the plastic and are found in body fluids and the general environment. Plasticizer

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