cyproterone and Precancerous-Conditions

The present study was undertaken to determine the effect of two different types of liver cell proliferative stimuli, namely compensatory regeneration and direct hyperplasia on DNA synthesis of normal and preneoplastic isolated hepatocytes. Platelet-poor plasma (PPP) isolated from male Wistar rats treated with three different hepato-mitogens, lead nitrate (LN), cyproterone acetate (CPA) and ethylene dibromide (EDB), or subjected to surgical partial hepatectomy (PH), was tested for its ability to stimulate DNA synthesis in normal and preneoplastic hepatocytes in primary cultures. Induction of DNA synthesis was detected as early as 30 min after CPA, EDB and PH administration and persisted up to 5 days after the LN administration. In addition, hepatocytes isolated from preneoplastic liver nodules were also able to respond in culture to the DNA synthesis stimulus induced by these factors.

Topics: Animals; Cell Division; Cells, Cultured; Cyproterone; Cyproterone Acetate; DNA; Ethylene Dibromide; Growth Substances; Lead; Liver; Liver Neoplasms, Experimental; Male; Mitogens; Nitrates; Precancerous Conditions; Rats; Rats, Inbred Strains; Stimulation, Chemical

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-glutamyl-transpeptidase (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-positive foci after Naf is due to a phenotypic change resulting in a suppression of GGT expression rather than to physical elimination of foci.

Topics: Animals; Body Weight; Carcinogens; Cell Survival; Clofibrate; Cyproterone; Cyproterone Acetate; Female; Glutathione Transferase; Hexachlorocyclohexane; Liver; Liver Neoplasms, Experimental; Nafenopin; Nitrosamines; Organ Size; Phenobarbital; Phenotype; Precancerous Conditions; Propionates; Rats; Rats, Inbred Strains

Numerous drugs, hormones and environmental pollutants induce liver growth by hypertrophy and/or hyperplasia, and promote preferential growth of putative preneoplastic foci in the liver. In the present study the regression of hyperplasia after cessation of inducer/promoter treatment was studied in normal liver and in liver foci. High doses of cyproterone acetate (CPA), a synthetic sex steroid, were administered to rats and produced a doubling of liver size; after cessation of treatment liver size declined, and 27% of the total liver DNA disappeared within 6 days. In histological sections from the involuting liver no necroses, but numerous apoptotic bodies (ABs) were found; retreatment with CPA interrupted the formation of ABs. These findings suggest that elimination of excess liver DNA after cessation of CPA treatment is due to controlled cell death by apoptosis. In a further series of experiments putative preneoplastic foci were produced by a single dose of N-nitrosomorpholine and subsequently stimulated to grow by 10 or 28 weeks of phenobarbital (PB) treatment. After withdrawal of PB numerous ABs were present in normal liver and in the foci; in both, retreatment with PB decreased the appearance of ABs. It appears that inhibition of cell death by PB may contribute to tumour promotion. Under all conditions tested more ABs were found in the foci than in non-focal parts of the liver, suggesting an enhanced cell turnover in foci. The apparent sensitivity of foci to mechanisms controlling cell death might eventually provide a means for elimination of preneoplastic lesions.

Topics: Animals; Antineoplastic Agents; Carcinogens; Cyproterone; Cyproterone Acetate; Female; Liver; Liver Neoplasms, Experimental; Precancerous Conditions; Rats; Rats, Inbred Strains

Topics: Animals; Carcinogens; Cell Division; Cyproterone; Cyproterone Acetate; Eating; Female; Hexachlorocyclohexane; Liver; Liver Neoplasms; Male; Mitotic Index; Nitrosamines; Precancerous Conditions; Progesterone; Rats; Rats, Inbred Strains

Topics: Animals; Carcinogens; Cell Division; Cyproterone; DNA, Neoplasm; Female; gamma-Glutamyltransferase; Hexachlorocyclohexane; Liver; Liver Neoplasms; Neoplasms, Experimental; Precancerous Conditions; Rats

Case-report about a 56 year old white female patient with pachydermia laryngis and hirsutism, successfully treated with cyproterone-acetate, a testosterone antagonist. The significance of androgenic hormones for the development of epithelial changes in the female larynx is emphasized. The administration of antiandrogenic substances as a new therapeutic measure is discussed.

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Cyproterone; Estrogens; Female; Hirsutism; Humans; Laryngeal Neoplasms; Middle Aged; Precancerous Conditions; Testosterone; Vocal Cords