Biomaterial Database

Peroxisome proliferator-activated receptors (PPARS) and carcinogenesis. 1999

J P Vanden Heuvel

Department of Veterinary Science, Penn State University, University Park, Pennsylvania 16802, USA. jpv2@psu.edu

Peroxisome proliferators (PPs) are an important group of chemicals that include certain hypolipidemic drugs, plasticizers and pollutants. Many of these agents are known rodent liver tumor promoters and debate exists as to whether humans are at increased cancer risk following exposure to PPs. Research over the last decade has focused on determining the biochemical and molecular mechanisms by which peroxisome proliferators exert their effects, in the hope that this controversy will be settled. PPs regulate gene expression via a steroid hormone receptor, the peroxisome proliferator-activated receptor (PPAR). At least three subtypes of PPAR (alpha, beta and gamma) have been cloned from several species, including humans. These receptors have been implicated in tumor promotion, cellular differentiation, and apoptosis. In the present article, the current understanding of how PPARs are involved in tumorigenesis, and what this may mean to human risk assessment, will be discussed.

UI	MeSH Term	Description	Entries
D008934	Mitogens	Substances that stimulate mitosis and lymphocyte transformation. They include not only substances associated with LECTINS, but also substances from streptococci (associated with streptolysin S) and from strains of alpha-toxin-producing staphylococci. (Stedman, 25th ed)	Mitogen,Phytomitogen,Phytomitogens
D009687	Nuclear Proteins	Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.	Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D002273	Carcinogens	Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.	Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014157	Transcription Factors	Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.	Transcription Factor,Factor, Transcription,Factors, Transcription
D018160	Receptors, Cytoplasmic and Nuclear	Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.	Cytoplasmic Receptor,Cytoplasmic and Nuclear Receptors,Cytosolic and Nuclear Receptors,Hormone Receptors, Cytoplasmic,Hormone Receptors, Nuclear,Nuclear Hormone Receptor,Nuclear Receptor,Nuclear and Cytoplasmic Receptors,Cytoplasmic Hormone Receptors,Cytoplasmic Receptors,Cytosol and Nuclear Receptors,Intracellular Membrane Receptors,Nuclear Hormone Receptors,Nuclear Receptors,Receptors, Cytoplasmic,Receptors, Cytosol and Nuclear,Receptors, Cytosolic and Nuclear,Receptors, Intracellular Membrane,Receptors, Nuclear,Receptors, Nuclear and Cytoplasmic,Hormone Receptor, Nuclear,Membrane Receptors, Intracellular,Receptor, Cytoplasmic,Receptor, Nuclear,Receptor, Nuclear Hormone,Receptors, Cytoplasmic Hormone,Receptors, Nuclear Hormone
D018570	Risk Assessment	The qualitative or quantitative estimation of the likelihood of adverse effects that may result from exposure to specified health hazards or from the absence of beneficial influences. (Last, Dictionary of Epidemiology, 1988)	Assessment, Risk,Benefit-Risk Assessment,Risk Analysis,Risk-Benefit Assessment,Health Risk Assessment,Risks and Benefits,Analysis, Risk,Assessment, Benefit-Risk,Assessment, Health Risk,Assessment, Risk-Benefit,Benefit Risk Assessment,Benefit-Risk Assessments,Benefits and Risks,Health Risk Assessments,Risk Analyses,Risk Assessment, Health,Risk Assessments,Risk Benefit Assessment,Risk-Benefit Assessments
D020025	Peroxisome Proliferators	A class of nongenotoxic CARCINOGENS that induce the production of hepatic PEROXISOMES and induce hepatic neoplasms after long-term administration.	Proliferators, Peroxisome