Sex-specific induction of apoptosis by cyproterone acetate in primary rat hepatocytes.

  title={Sex-specific induction of apoptosis by cyproterone acetate in primary rat hepatocytes.},
  author={P. Kasper and L. Mueller},
  volume={20 11},
The synthetic steroid cyproterone acetate (CPA) has been reported to be hepatogenotoxic in female rats depending on sex-specific expression of a hydroxysteroid sulfotransferase (HST) which is involved in the bioactivation of CPA to reactive metabolites. In the present study the ability of CPA to initiate apoptosis in rat hepatocytes in vitro was investigated with respect to sex-specific effects and dependency on HST activity. Incubation of primary hepatocytes of female rats with CPA (0.1-30… Expand
No-effect level in the mutagenic activity of the drug cyproterone acetate in rat liver. Part II. Multiple dose treatment.
It is concluded that the risk of humans to develop mutations under treatment with CPA is substantially lower than in the female rat, and a basis to estimate the risk to developed mutations in human liver following treatment withCPA is offered. Expand
Mechanism of action of liver growth induced by peroxisome proliferators
Ciprofibrate altered the expression of numerous genes including previously known PPARa agonist-responsive genes involved in processes such as PPAR signalling pathways, fatty acid metabolic pathway, cell cycle, palmitoyl-CoA hydrolase activity, lipid metabolism, inflammatory responses, and stress responses, in addition to a large number of novel candidate genes. Expand
Anti-genotoxic effect of Ocimum sanctum L. extract against cyproterone acetate induced genotoxic damage in cultured mammalian cells.
The results of the present study suggest that the plant infusion per se does not have genotoxic potential, but can modulate the genotoxicity of cyproterone acetate on human lymphocytes in vitro. Expand
Antigenotoxic role of Centella asiatica L. extract against cyproterone acetate induced genotoxic damage in cultured human lymphocytes.
The results of the present study suggest that the plant extract per se do not have genotoxic potential, but can modulate the genotoxicity of CPA on human lymphocytes in vitro. Expand
A role for GR-inducible C/EBPα and C-EBPβ expression in the transactivation of hepatic SULT2A-40/41 expression is supported. Expand
Apoptosis in Bcl2l13 Epididymal Cells of Mice
Apoptosis, i.e., controlled cell death, occurs in response to many different environmental stimuli and it plays an indispensable role in the development and maintenance of homeostasis within allExpand
A review of the common properties of drugs with idiosyncratic hepatotoxicity and the "multiple determinant hypothesis" for the manifestation of idiosyncratic drug toxicity.
  • Albert P. Li
  • Biology, Medicine
  • Chemico-biological interactions
  • 2002
Common properties of drugs that cause idiosyncratic liver toxicity are reviewed and it is proposed that these common properties may be useful experimental endpoints for the prediction and therefore avoidance of the selection of drug candidates with idiosyncratic drug toxicity for further development. Expand


Comparative study of DNA repair induced by cyproterone acetate, chlormadinone acetate and megestrol acetate in primary cultures of human and rat hepatocytes.
It is suggested that for these sex steroids extrapolation to humans of results obtained in rats might be questionable, as the amounts of DNA repair elicited by the three progestins in primary hepatocytes from female rats were similar. Expand
DNA-damaging activity of the cyproterone acetate analogues chlormadinone acetate and megestrol acetate in rat liver.
The findings suggest that the high genotoxicity of CPA is associated with the presence of the 1,2 alpha-methylene group, which is absent in CMA and MGA. Expand
In vitro mutagenicity studies on cyproterone acetate using female rat hepatocytes for metabolic activation and as indicator cells.
The synthetic sex steroid cyproterone acetate (CPA) was shown to induce DNA repair in primary hepatocytes from female rats, confirming previous reports about a sex-specific genotoxic potential of CPAExpand
Steroidal drug cyproterone acetate is activated to DNA-binding metabolites by sulfonation.
The assumption that sulfonation plays a decisive role in the bioactivation of CPA is further supported by the results obtained with an in vitro system consisting of calf thymus DNA, various subcellular liver fractions, and the cofactor PAPS, NADPH, or NADH. Expand
Accumulation and persistence of DNA adducts of the synthetic steroid cyproterone acetate in rat liver.
It is shown that CPA induces DNA adducts in rat liver; binding of the steroid is much higher in female compared to male rats, and as a consequence of their long half life, CPA-DNAAdducts accumulate significantly in the liver of rats. Expand
Adaptive responses of rat liver to the gestagen and anti-androgen cyproterone acetate and other inducers. II. Induction of growth.
Treatment of female Wistar rats with cyproterone acetate (CPA) leads to considerable enlargement of the liver. The organ content of water, dry mass, protein, RNA, and DNA increased in parallel withExpand
Cyproterone acetate generates DNA adducts in rat liver and in primary rat hepatocyte cultures.
The present findings show that CPA causes damage to hepatic DNA not only in vitro, but also in vivo, and it appears possible that DNA adduct formation is involved in the formation of hepatic tumors during long-term treatment of rats with the synthetic steroid. Expand
Cyproterone acetate induces DNA damage in cultured rat hepatocytes and preferentially stimulates DNA synthesis in gamma-glutamyltranspeptidase-positive cells.
Results indicate that CPA is not only a tumor-promoting, but also a genotoxic chemical, i.e. that it might also have an initiating potential. Expand
The non-genotoxic hepatocarcinogen nafenopin suppresses rodent hepatocyte apoptosis induced by TGFbeta1, DNA damage and Fas.
The ability of nafenopin to protect hepatocytes from apoptosis is not restricted to species or apoptotic stimulus and it is possible, therefore, that the PPs may suppress apoptosis by acting on diverse signalling pathways, but it seems more likely that nafinopin suppresses hepatocyte apoptosis elicited by each death stimulus by impinging on a core apoptotic mechanism. Expand
Species differences in response to peroxisome proliferators correlate in vitro with induction of DNA synthesis rather than suppression of apoptosis.
The ability of nafenopin to suppress apoptosis in mouse, hamster, guinea pig and rat hepatocytes and induce S-phase in mouse and rat liver tumour promoter, phenobarbitone is described. Expand