FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3025535175> ?p ?o ?g. }

• W3025535175 abstract "An investigation into the early cell biology changes in response to non-genotoxic carcinogens was carried out. The hypolipidaemic drug and peroxisome proliferator, clofibric acid was found to produce a significant hepatomegaly and to induce rat hepatic cytochrome P4504A isozyme(s) and peroxisomal β-oxidation at both the protein and molecular level. Also induced by this compound were the nuclear protooncogenes c-fos and c-myc, both of which are involved in the process of cellular growth control. This compound however, failed to increase transcription of the protooncogenes Ha-ras, Ki-ras, mos, ErbAl. It was concluded that the induction of c-myc and c-fos was related to the observed hepatomegaly and hypothesised that this induction may be characteristic of non-genotoxic carcinogens, in particular, peroxisome proliferators. Therefore, the specificity of this induction to clofibric acid and rat liver was investigated. The transcriptional activation of c-myc, c-fos and c-jun was examined in susceptible and non-susceptible species (rat and guinea pig respectively) and tissues (liver, kidney, heart and lung). The response of these species and tissues to clofibric acid was compared to their response to phenobarbitone. A marked induction of the aforementioned genes was apparent in those tissues which exhibited an increase in cell mass in response to the treatment regimes - there was no such correlation with tissues undergoing organelle proliferation or mixed function oxidase induction. Although the ability of peroxisome proliferators to induce sustained enhancement of cell proliferation correlates with the degree of carcinogenicity (Marsman et al, 1988, Bieri et al, 1986), it was concluded that the early proliferative responses examined here are not exclusively predictive of non-genotoxic carcinogenesis. Recent work has indicated that the Peroxisome Proliferator Activated Receptor (Issemann & Green, 1990) plays a key role in regulation of early gene changes involved in peroxisome proliferator-induced non-genotoxic carcinogenesis. I report the establishment of an in vitro model of peroxisome proliferator-associated effects in our laboratory and the use of this model to substantiate the PPAR-transfection work of Issemann et al (1993). I have demonstrated that the PPAR acts cooperatively with Retinoid X receptor in my in vitro model and dramatically increases the ability of PPAR to cause transcription of specific target genes including constitutive acyl CoA oxidase. In order to examine the regulation of the PPAR itself, one of the potential mechanisms for steroid hormone regulation, namely autoinduction, was investigated. The effect of a series of classical microsomal oxidase inducers (including peroxisome proliferators) on the abundance of PPAR mRNA was examined. My results strongly suggest that PPAR is inducible by those compounds known to be peroxisome proliferators (clofibrate and the perfluorinated fatty acids, PFDA & PFOA). Although no ligand binding to the PPAR has been shown to date, it is possible that the peroxisome proliferators themselves are ligands for the PPAR suggesting an autoregulatory mechanism of PPAR induction. Further, a functional correlation between PPAR induction and CYP4A1 transcription is suggested. It is hypothesised that the involvement of such a feedback loop readily explains the magnitude of enzyme induction response to peroxisome proliferators. The above results were used to draw conclusions as to the early stages of the mechanism of non-genotoxic carcinogenesis with a view to the definition of a diagnostic fingerprint for potential non-genotoxic carcinogens." @default.
• W3025535175 created "2020-05-21" @default.
• W3025535175 creator A5049518963 @default.
• W3025535175 date "1994-01-01" @default.
• W3025535175 modified "2023-09-24" @default.
• W3025535175 title "Cell Biology of Nongenotoxic Hepatocarcinogens." @default.
• W3025535175 hasPublicationYear "1994" @default.
• W3025535175 type Work @default.
• W3025535175 sameAs 3025535175 @default.
• W3025535175 citedByCount "0" @default.
• W3025535175 crossrefType "dissertation" @default.
• W3025535175 hasAuthorship W3025535175A5049518963 @default.
• W3025535175 hasConcept C104317684 @default.
• W3025535175 hasConcept C114246631 @default.
• W3025535175 hasConcept C127078168 @default.
• W3025535175 hasConcept C153911025 @default.
• W3025535175 hasConcept C181199279 @default.
• W3025535175 hasConcept C2779496979 @default.
• W3025535175 hasConcept C2779745421 @default.
• W3025535175 hasConcept C526171541 @default.
• W3025535175 hasConcept C55493867 @default.
• W3025535175 hasConcept C62112901 @default.
• W3025535175 hasConcept C86803240 @default.
• W3025535175 hasConceptScore W3025535175C104317684 @default.
• W3025535175 hasConceptScore W3025535175C114246631 @default.
• W3025535175 hasConceptScore W3025535175C127078168 @default.
• W3025535175 hasConceptScore W3025535175C153911025 @default.
• W3025535175 hasConceptScore W3025535175C181199279 @default.
• W3025535175 hasConceptScore W3025535175C2779496979 @default.
• W3025535175 hasConceptScore W3025535175C2779745421 @default.
• W3025535175 hasConceptScore W3025535175C526171541 @default.
• W3025535175 hasConceptScore W3025535175C55493867 @default.
• W3025535175 hasConceptScore W3025535175C62112901 @default.
• W3025535175 hasConceptScore W3025535175C86803240 @default.
• W3025535175 hasLocation W30255351751 @default.
• W3025535175 hasOpenAccess W3025535175 @default.
• W3025535175 hasPrimaryLocation W30255351751 @default.
• W3025535175 hasRelatedWork W122640819 @default.
• W3025535175 hasRelatedWork W1548860972 @default.
• W3025535175 hasRelatedWork W1969567327 @default.
• W3025535175 hasRelatedWork W1973419251 @default.
• W3025535175 hasRelatedWork W1980088139 @default.
• W3025535175 hasRelatedWork W1983733652 @default.
• W3025535175 hasRelatedWork W1986692426 @default.
• W3025535175 hasRelatedWork W2021992061 @default.
• W3025535175 hasRelatedWork W2056879555 @default.
• W3025535175 hasRelatedWork W2071305174 @default.
• W3025535175 hasRelatedWork W2084774843 @default.
• W3025535175 hasRelatedWork W2091528086 @default.
• W3025535175 hasRelatedWork W2118423087 @default.
• W3025535175 hasRelatedWork W2120728812 @default.
• W3025535175 hasRelatedWork W2124630453 @default.
• W3025535175 hasRelatedWork W2125388263 @default.
• W3025535175 hasRelatedWork W2134182089 @default.
• W3025535175 hasRelatedWork W2135231817 @default.
• W3025535175 hasRelatedWork W2162471694 @default.
• W3025535175 hasRelatedWork W2220828691 @default.
• W3025535175 isParatext "false" @default.
• W3025535175 isRetracted "false" @default.
• W3025535175 magId "3025535175" @default.
• W3025535175 workType "dissertation" @default.