Journal article

Publication year: 1990

Pages: 617-624

Journal: Carcinogenesis: Integrative Cancer Research

Volume number: 11

Issue number: 4

ISSN: 0143-3334

eISSN: 1460-2180

DOI Link: https://doi.org/10.1093/carcin/11.4.617

Publisher: Oxford University Press

Abstract: 
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 hexachlorocylohexane (HCH), or cytoproterone acetate (CPA), or nafenopin (Naf) or clofibrate (Clof), two hypolipidemic drugs. Foci were identified by a positive reaction for gamma-glutamyltranspeptidase (GGT) and other cytological markers. HCH 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. Immunohistochemical 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-postive foci after Naf is due to a phenotypic change resulting in a suppression of GGT expression rather than to physical elimination of foci.

Harvard Citation style: GERBRACHT, U., BURSCH, W., KRAUS, P., PUTZ, B., REINACHER, M., TIMMERMANNTROSIENER, I., et al. (1990) EFFECTS OF HYPOLIPIDEMIC DRUGS NAFENOPIN AND CLOFIBRATE ON PHENOTYPIC-EXPRESSION AND CELL-DEATH (APOPTOSIS) IN ALTERED FOCI OF RAT-LIVER, Carcinogenesis: Integrative Cancer Research, 11(4), pp. 617-624. https://doi.org/10.1093/carcin/11.4.617

APA Citation style: GERBRACHT, U., BURSCH, W., KRAUS, P., PUTZ, B., REINACHER, M., TIMMERMANNTROSIENER, I., & SCHULTEHERMANN, R. (1990). EFFECTS OF HYPOLIPIDEMIC DRUGS NAFENOPIN AND CLOFIBRATE ON PHENOTYPIC-EXPRESSION AND CELL-DEATH (APOPTOSIS) IN ALTERED FOCI OF RAT-LIVER. Carcinogenesis: Integrative Cancer Research. 11(4), 617-624. https://doi.org/10.1093/carcin/11.4.617