© 1990 Oxford University Press
research-article |
Effects of hypolipidemic drugs nafenopin and clofibrate on phenotypic expression and cell death (apoptosis) in altered foci of rat liver
1Institut für Tumorbiologie-Krebsforschung, Universiät Wien A-1090 Wien, Austria
2Institut für Toxikologie und Pharmakologie, Philipps—Universität Marburg
3Department of Toxikologie Schering AG, Berlin
4Institut für Veterinarpathologie, Universität Giessen FRG
5Present address: Institut für Biochemie und Endokrinologie, Universität Giessen FRG
6To whom correspondence should be addressed
Phenotypically altered liver foci were produced in female Wistar rats by a single dose of N-nitrosomorpholine followed by promotion with phenobarbital (PB) for 20 or 28 weeks. Then treatment was changed to either hexachlorocyclohexane (HCH), or cyproterone acetate (CPA), or nafenopin (Naf) or clofibrate (Clof), two hypolipidemic drugs. Foci were identified by a positive reaction for gamma-glutamyltranspeptidase (WT) and other cytological markers. MCH and CPA could substitute for PB as foci promoters; in contrast, Naf and Clof decreased expression of GGT in foci resulting in a decline of number and area of detectable foci, effects particularly pronounced with Naf. Immunohiso-chemical investigations of serial sections revealed that Naf also reduced expression of the altered phenotype when cytochrome P450-PB and pyruvate kinase (type L) were used as foci markers, but not when glutathione-S-transferase B (GST-B) was used. Thus, the number of foci with enhanced GST-B did not decline significantly after the change from PB to Naf treatment. Furthermore, the reduction of GGT and the decrease of foci number during Naf treatment were not associated with increased evidence of cell death by apoptosis in foci, in contrast to the situation after PB withdrawal. These findings strongly suggest that the disappearance of GGT-positive foci after Naf is due to a phenotypic change resulting in a suppression of GGT expression rather than to physical elimination of foci.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. A. Kramer, E. A.G. Blomme, R. T. Bunch, J. C. Davila, C. J. Jackson, P. F. Jones, K. L. Kolaja, and S. W. Curtiss Transcription Profiling Distinguishes Dose-Dependent Effects in the Livers of Rats Treated with Clofibrate Toxicol Pathol, June 1, 2003; 31(4): 417 - 431. [Abstract] [PDF]
|
|
|
|
 |
|
 J. M. Peters, I. Rusyn, M. L. Rose, F. J. Gonzalez, and R. G. Thurman Peroxisome proliferator-activated receptor {alpha} is restricted to hepatic parenchymal cells, not Kupffer cells: implications for the mechanism of action of peroxisome proliferators in hepatocarcinogenesis Carcinogenesis, April 1, 2000; 21(4): 823 - 826. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R Alison and C. E Sarraf Review : Apoptosis: regulation and relevance to toxicology Human and Experimental Toxicology, March 1, 1995; 14(3): 234 - 247. [Abstract] [PDF]
|
|
|
|
|
|
S. Green Receptor-Mediated Non-Genotoxic Carcinogenesis: New Models for Risk Assessment? Human and Experimental Toxicology, January 1, 1991; 10(6): 390 - 395. [PDF]
|
|